I HAVE THE DISTINCT PLEASURE OF
THE OPENING SESSION TO INTRODUCE
MY BOSS WHO IS AN AMAZING GUY
AND THE REASON I CAME TO NIH.
DIRECTOR OF THE NATIONAL TO
BIOMEDICAL ENGINEERING.
HE HAS A PORTFOLIO RESEARCHER
PROGRAMS FOCUSING ON DEVELOPING
TRANSLATING PHYSICAL SCIENCE AND
COMPUTATIONAL TECHNOLOGIES AND
BIOLOGICAL MEDICINE.
BUT HE STARTED RIGHT WHEN COVID
19 HIT AND IT PLAYED A ROLE WITH
THAT GOT ALL THE COVID TESTING
ACROSS THE UNITED STATES.
1.$7 BILLION INITIATIVE THAT'S
WHAT HAPPENED HERE WITH
INVESTIGATORS ACROSS THE COUNTRY
HE DOES RUN AN ACTIVE RESEARCH
LAB HERE AND 2022 AND 2024 CLASS
WITH NATIONAL ACADEMY OF
ENGINEERING.
MY PLEASURE TO INTRODUCE BRUCE.
>> IT IS MY DISTINCT PLEASURE.
THANK YOU FOR ORGANIZING THIS
AND PUTTING IT UP SO QUICKLY
WITH YOUR TEAM.
IT IS REMARKABLE.
WE WILL GO BACK AND FORTH AND
TALK ABOUT THE GROWTH OF
BIOMEDICAL ENGINEERING AT NIH
WITH UNIQUE CONTRIBUTIONS.
OUR VISION FOR THE FUTURE WHICH
IS INCLUSIVE OF BUILDING BRIDGES
TO ENGAGE ALL OF YOU.
AND AS HAPPENED WITH NIH
DIRECTORS CONGRESS CAME HER WAY
AND SHE IS RESPONSIVE TO
CONGRESS WITH TIME COMMITMENTS
BAD SPACE TIME JUGGLERS YOU WILL
FIND OUT AND SHE AGREED TO COME
IN THROUGH ZOOM EVEN THOUGH SHE
IS VERY INTO DATA SCIENCE AND
ARTIFICIAL INTELLIGENCE, THIS IS
NOT A DIGITAL TWIN, I THINK.
I WILL TAKE A COUPLE OF MOMENTS
TO INTRODUCE HER.
SHE IS THE 17th DIRECTOR OF
NIH NOMINATED BY PRESIDENT BIDEN
AND CONFIRMED BY THE U.S. SENATE
ON NOVEMBER 7 AND TOOK OFFICE ON
NOVEMBER 9.
THE FIRST SURGEON AND SECOND
WOMAN TO HOLD THE POSITION AND
AS YOU WILL FIND OUT THE FIRST
BIOMEDICAL ENGINEER.
AS AN AGE DIRECTOR OVERSEAS THE
FUNDER OF IN THE WORLD 27
INSTITUTES CENTERS
50 BILLION-DOLLAR ANNUAL BUDGET
AND PREVIOUSLY SERVED AS A 16th
DIRECTOR FROM THE NATIONAL
CANCER INSTITUTE IN PRIOR TO
JOINING NIH PROFESSOR OF SURGERY
AT HARVARD MEDICAL SCHOOL 2007
THROUGH 2018.
THROUGHOUT HER CAREER AT THE
FOREFRONT OF THE CAREER OF
CLINICAL ONCOLOGY.
ADVANCING CANCER DEVELOPMENT AND
AS A PROMOTER OF CANCER GROWTH.
HER BIO SAYS THE PHYSICIAN
SCIENTISTS BUT I WILL SAY
PHYSICIAN ENGINEER THE
INITIATIVES TO TRANSFORM DATA
INFRASTRUCTURE AND DATA SCIENCE
FOR CLINICAL RESEARCH HER HONORS
INCLUDE THE BOARD OF DIRECTORS
OF THE AMERICAN SOCIETY OF
CLINICAL ONCOLOGY AND THE
AMERICAN CANCER SOCIETY TO
PREVENT CANCER FOUNDATION AND
THE NATIONAL ACADEMY OF
MEDICINE.
MONICA GREW UP ON A RANCH IN
SOUTHWEST WYOMING WHICH IS A
FERTILE ENVIRONMENT FOR
ENGINEERING EXPERIMENTS IN
DISCOVERY AND GRADUATED FROM
PRINCETON WITH A BACHELOR OF
SCIENCE AND ENGINEERING.
AND WAS ACTUALLY A CLASSMATE
FROM OUR COLLEAGUE WHO ACTUALLY
HEADS NSF DIRECTOR AND FORMER
CHAIR BIOMEDICAL ENGINEERING AT
EMORY AND HER PREVIOUS BOSS.
UNDERGRADUATE RESEARCH STICKS
WITH YOU FOR YOUR ENTIRE LIFE I
KNOW SHE SEES THAT ALL THE
TIME.
AND AND MOST IMPORTANTLY MONICA
HAS A FAVORITE EQUATION 1 OF THE
FIRST QUESTIONS I ASKED LEARNING
ABOUT HER ENGINEERING BACKGROUND
AND DID NOT MISS A BEAT AND SAID
THE BRUNO THE EQUATION AND WHAT
WE CAN ALL RELATE TO WHEN YOU
COMBINE THIS GIVES A VERY STRONG
CASE TO CLAIM IS THE FIRST NIH
DIRECTOR WHO IS A BIOMETRIC --
-- BIOMEDICAL ENGINEER.
>> THANK YOU SO MUCH, BRUCE.
I WISH I WAS THERE IN PERSON
WITH YOU ALL TODAY.
MY BOSSES CALLED ME TO ANOTHER
LOCATION I'VE ALWAYS BEEN DRAWN
TO THEIR PROMISE OF BUILDING
THINGS.
I INTENDED TO BE A BIOMEDICAL
ENGINEER.
ACTUALLY IN THE SEVENTIES I WAS
IN COLLEGE WE DIDN'T HAVE
BIOMEDICAL ENGINEERING AS A
FIELD I HAD TO, TOGETHER WITH A
CHEMICAL ENGINEER AND
BIOCHEMISTRY SO I'M GLAD TO SEE
THAT HAS CHANGED.
BUT THEN I STARTED WORKING WITH
SOME INCREDIBLE PROFESSORS
APPLYING TO HUMAN CONDITION AND
HUMAN HEALTH.
I HAVE TO SAY TO HAVE AN
ENGINEERS APPROACH TO QUESTIONS
WHICH IS VERY UNIQUE AND
PRAGMATIC PROBLEM-SOLVING RATHER
THAN HIGH IN THE SKY AND NOT SO
PRACTICAL.
IT'S THRILLING TO BE WITH YOU
WITH THOSE WHO SHARE THE
PASSION.
THE WORK IS NOT FINISHED WHEN WE
HAVE SCIENTIFIC DISCOVERY OUR
WORK IS ONLY FINISHED WHEN WE
LIVE LONG AND HEALTHY LIVES AND
THAT IS WHY ENGINEERING HELPS US
TO.
I SUSPECT YOU ALL REALIZE HOW
THIS IS VERY PHYSICAL WITH THE
RIGHT APPROACH.
FROM THE NATIONAL ACADEMY OF
ENGINEERING SAYS SCIENTISTS
DISCOVER THE WORLD EXIST AND
ENGINEERS CREATE THE WORLD THAT
WILL BE.
NO SLOUCH WHEN IT COMES TO
BIOMEDICAL ENGINEERING THAT
15 PERCENT OF TOTAL BUDGET
SUPPORTS BIOENGINEERING.
AND ROUND OF APPLAUSE FOR HIS
ACCOMPLISHMENTS.
WHERE BRUCE HAS BEEN ABLE TO
BRING WITH THIS INSTITUTE IS
INTEGRATION WITH EVERY SINGLE
CORNER OF NIH TO BRING THE
ENGINEERING VIEW EVERY SINGLE
DISEASE CENTER AND ENTERPRISES
ACCOMPLISHING.
I WOULD LIKE TO HAVE A ROUND OF
APPLAUSE.
I BELIEVE FOR ENTREPRENEURS THE
GREATEST OPPORTUNITY IS NOT
BIOENGINEERING ACCORDING TO
MEDICARE SERVICES THIS IS ALMOST
$5 TRILLION ON HEALTH CARE IN
THE US.
SO IF YOU INVENT SOMETHING
USEFUL THAT IS A BIG WEDGE TO
TAP INTO AND ALSO AN INCREDIBLE
FIELD OF OPPORTUNITY FOR THINGS
THAT MAKE LIFE EASIER AND BETTER
WITH TREATMENTS AND PREVENTION
METHODS AND TO HELP US REDIRECT
TO THINGS THAT WORK OF COURSE IT
IS ENORMOUSLY GRATIFYING TO BE
IN THE FIELD TO MAKE AN ENORMOUS
DIFFERENCE FOR THE BETTER AND IN
SURGERY THE IMMEDIATE
GRATIFICATION IS A TREMENDOUS
DRIVER AND CAN DO THINGS THAT
WORK.
AS ENGINEERS ONLY IN TERMS OF
DISCOVERY BUT ALWAYS
IMPLEMENTATION AND FRANKLY WITH
THE MOST IN TERMS OF BETTER
HEALTH I AM DELIGHTED YOU ARE
VISITING THE CAMPUS IN BETHESDA
WE CAN ACCOMPLISH SO MUCH MORE
FOR THE NATIONAL RESEARCH
COMMUNITY INTERACTS BASED AT NIH
WE HAVE HER OWN PROGRAM HERE
WITH A LITTLE DIFFERENT APPROACH
HOW THEY ARE FUNDED AND
ORGANIZED BUT THERE IS A
TREMENDOUS AMOUNT OF BENEFIT TO
MORE INTERACTIONS SO THE GOOD
PARTS IN THE UNIQUE PARTS BOTH
CAN BE EFFECTIVELY LEVERAGE.
WITH CHEMISTRY AND ALL THE
DIFFERENT FORMS OF EXPERTISE TO
BENEFIT PEOPLE WHERE THEY ARE.
WE NEED MORE TOOLS TO HELP WOMEN
WERE EXPECTING BABIES BUT LIVING
IN MATERNAL HEALTH DESERTS.
AND WITH CUSTOMIZED HEALTHCARE
DECISIONS NOT NECESSARILY WHERE
PEOPLE HAVE MORE EASY ACCESS.
WE HAVE INFECTIOUS DISEASES THAT
INHABIT OUR BODIES.
WE CANNOT TELL RIGHT NOW WE ARE
TRYING TO CONQUER THE CHALLENGE
OF LONG COVID YOU HAVE METHODS
TO IDENTIFY WHETHER A PERSON HAS
REPLICATION CONFIDENT VIRUS IN
THEIR BODY BUT THAT WOULD BE
GREAT IF SOMEBODY CAN BREAK THAT
DIFFICULTY AND SO MUCH MORE
STILL NEEDS TO BE BUILT.
SO EVEN THOUGH I WAS CALLED TO
COME TO AND OTHERS SETTING BY A
MEMBER OF CONGRESS AND NOT ABLE
TO ATTEND I'M VERY GRATEFUL TO
BRUCE AND THE ENTIRE TEAM WHO
MADE POSSIBLE TO ATTEND AT
THIS POINT I'M EXCITED
>> AND WE NEED DATA FROM THE
LARGEST RESEARCH UNIVERSITY.
FROM THE FULL SPECTRUM OF THE
PEOPLE THAT WE SERVE TO
UNDERSTAND HOW TO BETTER DELIVER
HEALTH.
>> IT SOUNDS THAT I DID NOT
ALWAYS ORGANIZE IT IN WAYS.
I PUBLISH MY PAPER I DID NOT
CARE WHAT WAS GOING ON WHY WOULD
SOMEBODY ELSE WANT MY DATA?
THAT WAS CRITICAL AND IS
CRITICAL YOU THINK ABOUT THAT
GOING INTO THE PROJECT SO YOU
DON'T HAVE TO WASTE TIME BECAUSE
IT EVERY DAY THE UNIVERSE IS
DIFFERENT.
SOMEBODY CANNOT FIGURE OUT TO
SAY THIS IS THE WAY ALL
BIOENGINEERING DATA SHOULD
LOOK.
YOUR COMMUNITY SAYS THESE ARE
THE TYPES OF DATA WE DEAL WITH
SO THEY CAN BE SHARED.
THAT'S A TASK FOR YOUR
COMMUNITY.
I URGE YOU TO THINK ABOUT THAT
EVERY TIME YOU START A PROJECT.
ONCE THE FORMATTING ABILITY TO
SHARE THE LANGUAGE AND THE
ALPHABET THEN NIH ITSELF WORKING
REALLY HARD FOR US TO DO MORE IN
TERMS OF TO BRING IN PEOPLE WHO
WANT TO ASK VERY CHALLENGING
QUESTIONS AND HAVE AN
ENVIRONMENT WHERE THEY CAN BRING
THEIR QUESTION AND WE HOPEFULLY
THROUGH PROGRAMS WE ARE BUILDING
CAN HELP THEM FIND THE DATA THEY
NEED AND THEN COLLABORATE WITH
OTHER RESEARCHERS BASED ON THE
DATA THAT HAS BEEN ACQUIRED AND
THEN ALSO WITH THE ANALYTIC
CAPABILITIES TO HANDLE THE
DATA.
THE ONLY PERSON IN THE WORLD WHO
KNOWS HOW TO USE THE BEST IS
YOU.
SO ALSO PERHAPS A WHOLE NEW
ATTITUDE TO COLLABORATION OF
WHAT WE DO THAT IS ABOUT DATA
COLLABORATION HOPEFULLY THEY
REMAIN FUNDED OR ABLE TO
COLLABORATE.
SO LOOK AT WHAT WE ARE ABLE TO
DO BECAUSE WE HAD ENGINEERS AND
CHEMISTS IN BASIC BIOLOGIST
BRINGING THE FIRST DATA SETS
TOGETHER.
AND THAT'S WHERE WE CAN BUILD
THIS.
AND LESLIE LIKE YOU I'M AN
ENGINEER MY APPROACH TO THE DATA
UNIVERSE IF YOU BUILD IT THEY
WILL COME BUT MY APPROACH IS USE
CASE AND DRIVEN AND DATA USE.
>> BAD IS AN AMAZING ANSWER BUT
ALSO IT SEEMS IT IS QUITE
INFORMATIVE WE ENJOYED HIS
ANSWERS YOU ARE GIVING SO NOW
ANOTHER QUESTION SO WHAT ARE
WAYS THAT YOU THINK NIH COULD
SUPPORT JUNIOR BIOMEDICAL
ENGINEERS?
WE HAVE SOME POSTDOC AND GRAD
STUDENTS AND BREAKING DOWN SILOS
THAT WE HAVE SEEN SO WHAT ARE
WAYS THEY COULD BE MOTIVATED TO
ESTABLISH CLINICIANS IN EARLY
STAGES COULD BE MOTIVATED TO
ESTABLISH THOSE RELATIONSHIPS
WITH BIOMEDICAL ENGINEERS?
T 12 NOTHING SUBSTITUTES FOR THE
COLLABORATION AND INTERPERSONAL
RELATIONSHIPS WITH MENTORS IN
THE FIELD.
BUT THAT CAR CANNOT GO WITHOUT
GAS IN THE TANK SO FUNDING IS
CRITICAL.
AND WE DO STRIVE TO DIRECT
FUNDING SPECIFICALLY TOWARD
JUNIOR RESEARCHERS.
I DON'T KNOW PEOPLE KNOW THIS
BUT MAYBE YOU DO, ESPECIALLY
LAST YEAR WHEN THE BUDGET WAS
TIGHT NIH ACROSS THE BOARD GIVES
SPECIAL PRIORITY TO JUNIOR
PEOPLE WHEN IT COMES TO FUNDING
FOR THEIR GRANTS.
SO BASICALLY IT'S NOT THAT IT IS
EASIER, IT IS TOUGH OR THAT THE
SCIENCE IS ANY LESS SO WE WILL
CONTINUE TO LOOK AT WAYS ON BOTH
SIDES WITH COMMUNITY AND
MENTORSHIP AND COLLABORATORS AND
ALSO GAS IN THE TANK WHICH IS
ESSENTIAL FOR ELECTRICITY AND
THE BATTERY.
MAYBE THAT'S THE MORE
APPROPRIATE THING TO SAY RIGHT
NOW.
[LAUGHTER]
>> MAYBE THE NEXT QUESTION IS
LINKED TO THAT BECAUSE SO MUCH
OF THE DYNAMIC IN GROWTH OF
BIOMEDICAL ENGINEERING IS MAYBE
NOT A WELL-KEPT SECRET BUT IT IS
PRETTY ASTOUNDING YOU HAVE BEEN
ON THE ADMISSIONS COMMITTEE SO
WE ARE REALLY LEADING THE WAY
FOR EDUCATING WOMEN ENGINEERS.
MUCH HAS CHANGED SINCE YOU
COMPLETED YOUR DEGREE.
MORE THAN 50 PERCENT OF
UNDERGRADUATE STUDENTS ARE WOMEN
AND THE TOTAL NUMBER OF
GRADUATES HAVE MORE THAN
QUADRUPLED SINCE THE EARLY
2000.
SINCE 2022 MORE THAN 6000 WOMEN
BIOMEDICAL ENGINEERS ARE JOINING
THE WORKFORCE EACH YEAR ROUGHLY
TWICE THE GROWTH RATE.
>> .
FIRST OF ALL THIS IS AMAZING BUT
THAT IS AMAZING ESPECIALLY IN
THE ENGINEERING FIELD BUT WHAT
IS THE POWER OF THE POSSIBILITY
YOU SEE WITH THE GROWTH OF WOMEN
ENGINEERS?
OTHER WAYS IT CAN IMPACT HEALTH
CARE?
HEALTHCARE DESERTS A NEW
TECHNOLOGIES WHAT DO YOU THINK
IS THE POSSIBILITY OF WHAT WE
ARE BUILDING.
>> I WILL TELL YOU A STORY.
WHEN I STARTED SURGERY IN THE
EIGHTIES I WAS THE ONLY WOMAN
AROUND.
I WANTED TO BE JUST LIKE THE MEN
BECAUSE THEY WANTED TO FIT IN
BUT I WAS STUPID I REALIZED
LATER ON THAT MY OWN VISION AND
VOICE WAS GOING TO BE
DIFFERENT.
I REALLY DO BELIEVE I COULD BE
FROM DIFFERENT
COMMUNITIES, WHATEVER.
WHATEVER IS INNATE TO YOU MAKES
YOU UNIQUE AND ABLE TO
CONTRIBUTE SOMETHING NOBODY ELSE
CAN.
SO I THINK IT IS THRILLING WE
HAVE HALF OF THE POPULATION
WHICH ARE WOMEN THAT REALLY DO
CONTRIBUTE DIFFERENTLY.
WE THINK DIFFERENTLY.
WE HAVE GOOD SCIENCE TO SHOW
THAT.
IT'S THRILLING TO SEE THOSE
CONTRIBUTIONS WHICH IN THE PAST
THAT WERE NOT THERE ARE NO
REALIZED.
>> THANK YOU FOR THAT I LOVE
THIS COMMUNITY WE ARE DIVERSE
AND SO MANY OTHER ACCESS.
SO SHARE YOUR PORTENTS OF
BIODIVERSITY IN SOLVING
COMPLICATED PROBLEMS.
>> EVERYONE BRINGS SUCH A UNIQUE
VIEWPOINT MY OWN PERSONAL
EXPERIENCE 100 MILES TO THE
GROCERY STORE BELIEVE IT OR NOT
IF I WAS TRYING TO COOK DINNER I
HAD USE WHAT WAS IN THE CUPBOARD
AND REFRIGERATOR AND IF
SOMETHING BROKE THERE IS NOBODY
THERE TO FIX IT BUT ME.
THAT IS A VERY DIFFERENT
BACKGROUND TO BRING TO THE
FIELDS THAT I ENTER OF
ENGINEERING AND SURGERY.
SUMMARIES ON THE OPERATING TABLE
YOU CANNOT SAY I NEED THIS TO BE
DIFFERENT OR PLUG-IN A NEW
COMPONENT.
ENGINEERS ARE MAKING THAT
POSSIBLE BUT IT WASN'T WHEN I
WAS DOING SURGERY.
SO WITH ANYBODY'S BACKGROUND
THAT IS DIFFERENT FROM WHAT WE
HAVE IT BRINGS EXCITEMENT AND
INNOVATION AND MUCH BETTER
SUCCESS.
>> WE HAVE 3 MINUTES BEFORE YOUR
NEXT ENGAGEMENT.
THIS IS FAST.
YOU MENTIONED TOOLS OR SOLVING
PROBLEMS AND WE LOVE TO DEVELOP
NEW TOOLS, DIAGNOSTIC ASSAYS AND
WE LOVE THAT STUFF.
BUT WE SUPPORT TOOLS THAT COULD
DO ANYTHING THAT THEY WANT TO BE
VALIDATED TO SOLVE PROBLEMS OF
THE INSTITUTES.
SOMETIMES WE HAVE A CHALLENGE.
DO YOU HAVE ANY THOUGHTS ON HOW
WE SHOULD PROGRESS IN THE
FUTURE?
WE HAVE TOOLS FOR PROBLEMS BUT
WE NEED TO CONNECT WITH OTHER
INSTITUTES SO WE GO AROUND IN
CIRCLES.
>> DR. BERTAGNOLLI: WE CAN FIX
THAT VERY QUICKLY.
I THINK WE HAVE WITH THE
PARTNERSHIP TO MORE THAN PROVEN
THE WORST OF WHAT IT DELIVERS
ACROSS ALL OF NIH NOW, IMPROVING
THE IMPLEMENTATION PHASE WITH
THE CLINICAL ENVIRONMENT THAT IS
HARD FOR EVERYBODY THAT'S HARD
FOR PEOPLE THAT DEVELOP NEW
DRUGS OR NEW DEVICES FOR
ANYTHING THAT WE DO 1 OF THE
THINGS WE ARE WORKING VERY HARD
ON IS A MUCH MORE EFFICIENT WIDE
CLINICAL RESEARCH TESTING
ENVIRONMENT.
SO BASICALLY YOU NEED BUT ALL OF
NIH NEEDS.
YOU ARE NOT UNIQUE.
YOU JUST HAVE MORE PATIENCE THAN
EVERYBODY ELSE WHICH I LOVE.
PEOPLE NEED US WE HAVE TO GO
FAST.
WE ARE WORKING ON IT AND I WILL
TELL YOU AND GIVE YOU A CLUE THE
EXAMPLES I GAVE YOU MATERNAL
HEALTH AND ELDERLY PEOPLE
HELPING WITH MOBILITY I WANT TO
TEST OF SOMEBODY'S MUSCLE MASS
IS GOING DOWN BECAUSE THAT IS
THE LEADING INDICATOR OF AN OLD
PERSON FALLING OFF THE EDGE ALL
OF THE WONDERFUL THINGS WE NOW
HAVE A NETWORK OF PRIMARY CARE
CLINICIANS TO BETTER TESTES WE
ARE LOOKING FORWARD TO APPLYING
THAT.
>> REMARKABLY ON TIME WHICH IS
UNCHARACTERISTIC FOR ME.
YOU HAVE A DIFFERENT CLOCK.
THANK YOU SO MUCH.
>> NEXT TIME I WILL BE THERE.
>> WE ARE SO GRATEFUL TAKING THE
TIME I KNOW YOU HAVE TRAVELS AND
TALKS THE REST OF THE DAY WITH
CHALLENGES AND WE ARE VERY
GRATEFUL FOR YOUR UNDERSTANDING
AND ADVOCACY THANK YOU.
>> DR. BERTAGNOLLI: GOODBYEER
EVERYBODY.
>> ALSO THANK YOU TO BRUCE.
THAT WAS FANTASTIC.
THE FIRST SURGEON DIRECTOR OF
NIH IN THE FIRST BIOMEDICAL
ENGINEER AND YOU CAN HEAR HER
SUPPORT WHAT WE ARE DOING IN THE
WAY WE ARE BUILDING
RELATIONSHIPS.
BUT NOW WE WILL GET INTO THE
SCIENCE PART BUT BEFORE WE DO
THE SCIENCE THANK YOU FOR COMING
AND THE MOTIVATION TO GET NIH
RESEARCHERS HERE ON CAMPUS TO
HAVE MORE EXTRAMURAL RESEARCH
YOU WILL HEAR THAT TERM ALL DAY
IF YOU DON'T WORK HERE THERE ARE
WAYS TO COLLABORATE ACROSS THE
WORKSPACES OF WHERE WE ARE SO
YOU WILL SEE EACH OF THE
BREAKOUT SESSIONS INTRAMURALS
SPEAKERS AND EXTRAMURAL SO WE
CAN ALL SEE EACH OTHER DURING
COLLABORATION.
SO JUST A QUICK POLL FIRST OFF
HOW MANY PEOPLE IS THAT THEIR
FIRST TIME HERE AT THE BETHESDA
CAMPUS?
LOOK AT THIS.
ALSO HOW MANY OF YOU ARE NIH
EMPLOYEES?
STAND UP IF YOU ARE ABLE.
AND FOR THOSE OF YOU WHO ARE NOT
EMPLOYEES THAT WORK IN THE SPACE
PLEASE STAND.
I LOVE THAT THEY ARE DISTRIBUTED
SO TALK TO YOUR NEIGHBOR AND SEE
WHERE THEY ARE SO NOW IT IS MY
GREAT PLEASURE TO INTRODUCE OUR
FIRST KEYNOTE SPEAKER THE
MORNING KEYNOTE AND I AM REALLY
EXCITED THAT HE IS AGREED TO DO
THIS TALK AS A LEADING
RESEARCHER FOR SICKLE CELL
DISEASE WHICH WAS MY MOTIVATION
TO MOVE TO NIH.
HE HAS BEEN ON THE FOREFRONT OF
MANY OF THOSE.
GRADUATING FROM THE COLLEGE OF
CHARLESTON AND A BA IN CHEMISTRY
AND THEN EARNED M.D. FROM
UNIVERSITY OF SOUTH CAROLINA
WORKING ON SICKLE CELL.
JOINED THE MOLECULAR HEMATOLOGY
BRANCH OF KIDNEY DECISIVE
DISEASES IN 1998 AND THEN IN
2011 RECOGNIZING HIM WITH THE
ALUMNI OF THE YEAR AWARD THE
PREMEDICAL SOCIETY AWARD OF
MEDICINE AND RECENTLY ELECTED TO
CLINICAL INVESTIGATIONS IS
CO-AUTHORED MORE THAN 140 PAPERS
I REALLY WANT HIM TO TALK TO THE
COMMUNITY HE'S PART OF THE
CLINICAL TEAM OF THE FDA SICKLE
CELL GENE THERAPY PROVIDED BY
FDA DECEMBER 2023 AND HIS
RESEARCH WAS A PART OF THAT.
I KNOW OUTSIDE THE COMMUNITY
EVERYBODY IS THINKING OF ALL THE
WAYS WE CAN TRANSFORM THE
THERAPIES AND HIS TEAM GOT THAT
THROUGH THE FDA.
MY PLEASURE TO INTRODUCE DOCTOR
TISDALE.
[APPLAUSE]
GREAT.
THANK YOU FOR THE OPPORTUNITY TO
BE HERE.
THANK YOU TO THE ORGANIZERS FOR
ALLOWING ME TO SHOW HER WORK.
I WILL HIT THE HIGHLIGHTS OVER
THE LAST 30 YEARS MEANING I WILL
SKIP THE STUFF THAT DID NOT WORK
OR AT LEAST MOST OF IT WHICH
LEAVE ME WITH ABOUT 45 MINUTES
OF DATA.
LET'S GET STARTED.
I LIKE TO START OFF BY SAYING IT
IS TIME WE CONTEMPLATE FOR
SICKLE CELL WE HAVE KNOWN ABOUT
IT FOR MORE THAN A CENTURY THE
FIRST MOLECULAR DISEASE
RESULTING FROM AN ABNORMAL
HEMOGLOBIN.
AND THE RESULTS FROM 1 LETTER
OFF AND THEN YOU HAVE A DISEASE
THAT MAKES THE HEMOGLOBIN PRONE
AFTER THE OXYGENATION AND THE
CELLS ARE STUCK IN CIRCULATION
IN WEEK HAVOC FROM HEAD TO TOE.
IT IS ALSO CONSIDERED A RARE
DISEASE IN THE US BUT IN THE
WORLD IT IS NOT THERE ARE MAYBE
30 OR 40 MILLION IN THE WORLD
AND OUR CURRENT THERAPIES ARE
LIMITED.
'S THIS USED TO HAVE 4 THAT THE
FDA APPROVED THE 1 WAS PULLED
FROM THE MARKET JUST BECAUSE
AFTER APPROVAL IT DID NOT SEEM
TO MEET THE PROMISE AND NOW THE
SECOND HAS BEEN PULLED AND
EUROPE.
SO WE REALLY NEED CLINICAL
TRIALS FOR THESE APPROACHES SO
THE DISEASE AFFECTS ORGANS FROM
HEAD TO TOE TO THE CIRCLE OF RED
CELLS CAUSING STROKES AND THE
PRINCE OF OLD MANIFESTATION IS
PAIN IN BONES OR MUSCLES WHERE
BLOOD FLOW IS OCCLUDED AND ALSO
SHORTENS THE LIFESPAN.
WITH A MEAN AGE OF DEATH 39 AND
THE MOST RECENT SERIES SHOWS IN
2006 THE STUDY WAS STONE DONE
AFTER UNIVERSAL NEWBORN
SCREENING.
SO IT IS A BAD DISEASE AFFECTING
EVERY ORGAN YOU ARE IN THE
HOSPITAL ALL THE TIME WITH PAIN.
QUALITY IS NOT ONLY AFFECTED BUT
THE LIFESPAN IS AFFECTED.
SO THESE ARE THE TREATMENTS THAT
I DESCRIBE SOME YEARS AGO FIRST
IS BIOENGINEERING YOU CAN SEE
THOSE BLOOD CELLS AND SO IF WE
COULD COME UP WITH THE DRUG TO
NOT POLYMERIZE SO QUICKLY THEY
COULD MAKE IT THROUGH WITHOUT
INCLUDING SO THEN BY REACTING
FETAL HEMOGLOBIN AND THAT
PREVENTS CIRCLING TO GET THOSE
AROUND AND REDUCE THE NUMBER OF
PAIN EVENTS THAT PATIENTS HAVE.
SO IF YOU JUST REPLACE THE WHOLE
FACTORY WHERE BLOOD IS MADE YOU
CAN ALSO FIX THE DISEASE SO WE
CAN DO THAT WITH FAMILY MEMBERS
WITHIN THE CURRENT TREATMENTS
WITH THE VIRUS THAT DENIGRATES
AS A FACTOR THAT I HAVE HAD TO
MOVE THAT BECAUSE THEY BOTH ARE
JUST FDA APPROVED IN DECEMBER OF
LAST YEAR.
SO HOW DOES THIS WORK?
THE TRANSPLANTS REPLACE THE
SCENES OF THE BLOOD AND SINCE
ALL CELLS OF CIRCULATION IF WE
REPLACE GIVE SOMEBODY ELSE'S OR
REPAIR GIVING THEM THEIR OWN
THEN WE CAN FIX THE DISEASE TO
MAKE NORMAL HEMOGLOBIN SO THAT'S
WHAT WE HAVE BEEN UP TO OVER THE
LAST 3 DECADES TO FIGURE THIS
OUT.
WHEN I CAME ON THE SCENE IN THE
EARLY NINETIES IT WAS JUST SHOWN
A TRANSPLANT FROM A BROTHER OR
SISTER CAN CURE THE DISEASE BUT
NORMALLY WE LOOK AT SOMETHING
FOR LIKE THIS WITH LEUKEMIA AND
THEY HAVE A TRANSPLANT ALSO HAS
SICKLE CELL AND WAS CURED OF
BOTH AND THAT LED TO EFFORTS TO
START DOING THIS ON PURPOSE WITH
PATIENTS AND USING THE STANDARD
HIGH-DOSE TO WIPE OUT THE BONE
MARROW AND WIPING OUT THE IMMUNE
SYSTEM AND THEN SOMEBODY ELSE'S
BONE MARROW WITH
IMMUNOSUPPRESSION AND IT WORKED
MOST OF THE TIME THE SURVIVAL
RATE IS MOST OF THE TIME AND
THEN JUST BY DOING IT WE GOT
BETTER SO TO GET THE STANDARD
REGIMEN 93 PERCENT THEY ADDED 1
ANTIBODY TO GET RID OF THE T
CELLS AND YOU CAN SEE THE
REJECTION RATE GOES FROM
22 PERCENT TO 3 PERCENT AND NOW
JUST WITH BETTER MANAGEMENT THE
CURE RATE IS OVER 95 PERCENT.
AND HERE YOU CAN SEE AFTER 2000
IT IS 95 PERCENT.
I SAID YOU SHOULD GET THE
TRANSPLANT YOU HAVE A SIBLING.
BUT MARK WALTERS AFTER HIS FIRST
STUDY SHOWS SOMETHING THAT IS
IMPORTANT TO US IS THAT EVEN
WHEN THEY TRY TO MAP BONE MARROW
COMPLETELY SOME PATIENTS STILL
HAVE THERE'S REMAINING SO
PRESUMABLY THEY ARE SO MAKING
SICKLE CELLS BUT IF YOU LOOK AT
THE BLOOD ALL OF THE RED BLOOD
CELLS WERE DONOR TYPE.
EVEN 11 PERCENT WHITE CELLS IT
IS ASSOCIATED WITH ALL OF THE
RED CELLS.
SO WE THOUGHT CAN WE DO THIS ON
PURPOSE?
SO THIS IS WHAT I'M THINKING AT
THE TIME.
SO IF YOU GIVE CONDITIONING GO
ALL THE WAY OVER TO THE GREEN
CELLS WHICH ARE THE DONOR
CELLS.
WHAT IF YOU DON'T COMPLETELY YOU
GET MAKE SURE THAT IS SUFFICIENT
TO MAKE ALL THE RED CELLS.
SO CAN WE DO THIS ON PURPOSE?
AND WE WERE LOOKING AT PATIENTS
WITH CANCER WE COULD DO THIS BUT
WE STILL HAD TOO MUCH FROM
ANOTHER DISEASE THAT WAS A
SEVERE A SICKLE CELL SO AFTER A
LOT OF WORK WITH SMALL AND LARGE
ANIMALS LOOKING AT LOW DOSES OF
RADIATION WE CAME UP WITH THE
REGIMEN WE USED RAPAMYCIN
BECAUSE IT BLOCKS THE SECOND
LEVEL OF T CELL ENGAGEMENT AND
INDUCING TOLERANCE AND IN FACT
IT CAN BLOCK THE TOLERANCE
THROUGH RAPAMYCIN.
AS A MEDICAL STUDENT WORKING
HERE WITH THE BOWS MODEL SO WE
INCREASE THE RADIATION DOSE A
LITTLE BIT WE THOUGHT WE NEEDED
A LITTLE MORE PRESSURE AND ADDED
AN ANTIBODY TO THE LYMPHOCYTES
TO HOPEFULLY PREVENT THE HOST
DISEASE NOW 9 OF THE FIRST 10
HEMOGLOBIN ENDS ARE NO - -
NORMALIZED AND MIXED I SHOWED
GREEN AND BLUE BUT ALL REMAINED
ON IMMUNOSUPPRESSION WE GOT A
LOT OF SLACK SO WE WROTE THE
RULES WE HAVE NORMAL HEMOGLOBIN
AND WE WILL BE THESE AND THOSE
ARE EXTENDED WE SAW A
NORMALIZATION OF THE HEMOGLOBIN
THOSE WITH REPLACEMENT OF NORMAL
RED CELLS HAD PAIN GO AWAY.
I LIKE TO SHOW THIS THOSE THAT
WERE THOUGHT TO BE DRUG ADDICTS
JUST COMING TO THE ER TO GET
PAIN MEDICATION.
IF YOU MAKE THE PAIN GO AWAY
THEY DON'T COME BACK.
AND HERE IS ANOTHER PROOF OF THE
NOTION SHOWING THE
HOSPITALIZATION THAT IS OVER 3
PER YEAR AND THAT INCLUDES HIP
REPLACEMENTS AND OTHER THINGS
AND IMPORTANTLY THOSE ABOVE THE
LINE 50 PERCENT OF THE DONOR
THEY WERE WEANED BUT ON THE
RIGHT IT IS THE MYELOID SERIES.
AND THERE IS NO DIFFERENCE
BETWEEN THE 2 WHETHER THEY
REMAIN.
AND WITH THAT RETROSPECTIVE
STUDY WITH A NAGGING PROBLEM
10 PERCENT OF GRAPH PROJECT ANDS
THE MADDOX STEMM CELLS.
AND THE SURVIVAL THAT IT
SYNERGIZES AND THAT IS TO FULL
DONOR.
IT IS LOW TOXICITY THAT ALLOWS
US AND THAT WAS CRUCIAL BECAUSE
KIDS CAN TOLERATE SOME PLAYED IS
CHEMOTHERAPY.
BECAUSE PARENTS DON'T WANT TO
RENDER THEM INFERTILE.
THEY WAIT FOR THAT DECISION EVEN
IF THEY HAVE A DONOR UNTIL THE
KID IS THE -- -- AN ADULT MAKE
THE DECISION BUT BY THE TIME
THEY ARE AN ADULT THEY HAVE AND
OREGON DAMAGE SO THAT MAKES THEM
INELIGIBLE NOW THEY CANNOT GET A
TRANSPLANT BECAUSE THEY ARE 26
-- -- TOO SICK.
WITH ALL OF THE THINGS WE HAVE
DONE MOST PATIENTS DON'T HAVE A
DONORS ONLY 10 PERCENT WE LOOK
AT UNRELATED AND THAT IS LIMITED
BECAUSE OF THE POPULATION IT IS
HARD TO FIND A MATCH SO NOW THE
TRANSPLANTS EFFORTS ARE ONGOING.
AND THIS HAS ACTUALLY BEEN QUITE
SUCCESSFUL.
IF YOU HAVE A PARENT OR A CHILD
IS A HALF BATCH AND A SIBLING IS
A 50 PERCENT CHANCE THEY ARE
HALF MATCH.
ALL THE PATIENTS SURVIVED.
LITTLE TWEAKS HERE AND THERE MAY
GET BETTER OVER THE YEARS.
AND THIS ALLOWED US TO LOOK BACK
AND SAY HOW ARE WE DOING WITH
TRANSPLANT FOR RESEARCH WHERE
ALL THE DATA ARE TRANSPLANTED?
ABOUT 1000 PATIENTS HAVE BEEN
TRANSPLANTED IN THE DECADE BUT
ALL OF THESE ARE LOOKING SIMILAR
EVENT FREE OR DISEASE-FREE
SURVIVAL IS GETTING PRETTY
GOOD.
MOST PEOPLE WOULD BE HAPPY WITH
THESE KINDS OF NUMBERS
ESPECIALLY CANCER BUT WE HAVE TO
MAKE THE'S BETTER AND SIMPLE
WAYS TO MAKE THE HALF MATCH
BETTER.
HOPKINS GROUP JUST INCREASED
RADIATION DOSE FROM 200 AT 400
AND WENT FROM 50 PERCENT TO OVER
90.
ONLY 17 OF THE SUBJECTS REJEC
REJECTED.
THAN THE VANDERBILT GROUP AND
THE ADULT COHORT IN RED WITH THE
EVENT FREE SURVIVAL IS NEARLY
100 PERCENT IT IS QUITE
INCREDIBLE WITH A LITTLE TWEAK
AND IN THIS CASE THEY DID NOT
INCREASE RADIATION BUT JUST
ADDED A CHEMOTHERAPY DRUG.
WE KNOW IT WORKS.
SO WHAT IF WE TOOK THE PATIENT'S
OWN CELLS HOW MANY WOULD BE HAVE
TO FIX TO MAKE THIS WORK?
SO WHEN IT WAS GO TIME WE
TRANSPLANTED MORE THAN 100
PATIENTS AND 3 UNFORTUNATE
PATIENTS WHO HAVE THE PERCENTAGE
OF THEIR WHITE CELLS IN THE
MYELOID SERIES SO THAT REFLECTS
THE HEMATOCRIT STEMM CELL AND
WHEN THEY GET THE 20 PERCENT
MARK 1 OUT OF 5 OF THE STEMM
CELLS COMING FROM DONORS THEY
HAD DISEASE RECURRENCE.
SO IF WE ARE OVER 20 PERCENT WE
SHOULD FIX THIS DISEASE WE CAN
GET A BOOST OF THE STEMM CELLS
AND GET THEM BACK AND OUT OF
MISCHIEF SO WHY IS IT IF YOU
HAVE A MUCH BETTER LIFESPAN THAT
WILL BEAT OUT THE ONES THAT
DON'T LIVE LONG.
SO TO COME UP WITH A
MATHEMATICAL MODEL THAT SAYS IF
IT IS LIFESPAN ONLY YOU SHOULD
SEE THIS BLUE LINE SO THAT'S
REAL DATA.
WHEN YOU GET 20 PERCENT IN RED
THE REAL DATA THE HEMOGLOBIN IS
50 PERCENT.
THEY HAVE HALF WHEN THEY GO
ABOUT 50, USING ONLY THE RED
CELL LIFESPAN SO THAT TELLS US
FORGET US 1 OUT OF 5 WE CAN FIX
THE DISEASE.
WE HAVE BEEN WORKING FOR A LONG
TIME TO GET AT 20 PERCENT AND IN
THE EARLY NINETIES I WAS EXCITED
BECAUSE WE COULD PUT GENES IN
AND GET 50 PERCENT ALL DAY IF WE
DO THE SAME THING TO HUMAN CELLS
WE START THE TRIALS IN HUMANS TO
LOOK FOR PATIENTS WERE GETTING A
BONE MARROW TRANSPLANT AND WE
HAVE REALLY LOW LEVELS OF
MARKING.
HIGHLY SENSITIVE TO DETECT 1 IN
A MILLION CELLS AND THAT'S WHAT
WE GOT WITHIN A 50 PERCENT BUT 1
IN A MILLION SO WE WERE WAY OFF
20 PERCENT.
WE HAVE TO FIGURE OUT TO GET 1
IN A MILLION FROM 1 OUT OF 5.
SO WE WOULD WORK THROUGH THE
CELL CULTURES BECAUSE THE LARGE
ANIMALS VERY PREDICTIVE OF WHAT
WE SEE IS NOT EVEN COMPETITIVE
REPOPULATION TO SERVE AS A GO OR
NO GO.
WE SPENT MOST OF THE TIME GOING
BACK TO THE DRAWING BOARD WE GET
THERE THINKING WE ARE READY.
1 OF THE IMPORTANT THINGS WE
FOUND WAS LOOKING AT THE STEMM
CELLS IT DRIVES THE LOSS AND
MOSTLY TO DIFFERENTIATE IF YOU
LOOK AT THE CULTURE PUTTING
THESE IN YOU WOULD SEE
NEUTROPHIL AND PLATELETS AND
THAT SORT OF STUFF.
BUT WE STARTED COMPARING WITH
THE POPULATION AND EXPANSION AND
WITH THE CELL NUMBER AND COLONY
SO WE HAVE THOSE IN VIVO BUT
THEN ALONG THE BOTTOM BACK AT
AROUND 5 PERCENT WHICH IS CLOSE
GOING FROM 1 IN A MILLION AT
5 PERCENT WAS HUGE.
AND THAT 5 PERCENT WITH SEVERE
COMBINED IMMUNODEFICIENCY SO
THIS IS THE FIRST GENE THERAPY
THAT WORKED USING THE IDENTICAL
CONDITIONS TO THE LAST CONDITION
COMPLETE CONSTITUTION OF THOSE
THAT HAVE THOSE TRIP STEMM CELLS
TRANSFUSED TO FIX THE DISEASE.
AND THEY HAD A FIX OF THEIR
DISEASE BUT THE RESULTS WERE
OVERSHADOWED BUT THERE ARE
RECURRENCE OF LEUKEMIA -- --
LEUKEMIA AND 3 OF THOSE IT IS
OUR RETROVIRAL FACTOR BECAUSE IT
INTEGRATES INTO THE DNA AND MOST
OF IT HAS VIRUS FEATURES BUT
THAT IS WHAT GETS IT INTO THE
CELLS AND VERY GOOD AT TURNING
ON THE GENES AND WITH THIS
FACTOR TYPE AND THEN TO SHOW THE
NEW VECTORS BASED ON AND HIV
COULD SOLVE A COUPLE OF
PROBLEMS.
1 IS THEY DID NOT SEEM TO CAUSE
INSERTIONAL.
THESE WERE NOT BECAUSE OF
INSERTIONAL MUTAGENESIS.
BUT THESE FACTORS MADE FROM HIV
THIS WAS HUGE FOR US BECAUSE IF
YOU DIVIDE THEM THEN YOU LOSE
THEM SO WE CAN USE THE
CONDITIONS AND USE THIS FACTOR
SYSTEM ALSO DELETIONS WHICH
RENDERS THEM AN ACTIVE AND WITH
INTEGRATION AND THAT IS FLANKED
WITH THE LTR.
THEY DON'T LAND LIKE RETROVIRAL
FACTORS.
WE NEED RED BLOOD CELLS TO MAKE
THIS WORK AND IN OUR CASE THE
NEXT STEP IS FOR THE PROBLEM
ANYWAY.
BUT THE OTHER BIG DEAL THESE CAN
PACKAGE ALL THE BITS THAT YOU
NEED WITH SPECIFIC EXPRESSION
ANY PARTS OF THE GENOME WITH THE
BETA GLOBIN AND WE CAN GIVE ALL
OF THAT INTO HIV WERE WE COULD
NOT AND THEN ALSO SHOW TO
CORRECT 2 DIFFERENT MODELS OF
SICKLE-CELL WITH THESE MODELS.
SO WE STARTED WORKING TO IMPROVE
THIS.
SO WE MADE THIS HIGHBRIDGE
VECTOR BECAUSE THAT WORKS FINE
IN THE MULTI- TEST ALL DIFFERENT
SORTS OF BETA GLOBIN AND
EXPRESSING VECTORS AND THE
REVERSE ORIENTATION AND THAT IS
WHAT WE NEED FOR GOOD
EXPRESSION.
WITH A 20 PERCENT MARK AT THE
MONKEYS SO WE LAUNCH THE TRIAL
WITH THE INDUSTRY COLLEAGUES FOR
DOING TRANSPLANTS TO TAKE IT
INITIALLY IN GROUP A AND PUT THE
VECTOR IN?
AND THAT IS SO CELLS TO GRAFT
AND REMAINING CELLS THEN THEY
ARE IN THE HOSPITAL FOR ABOUT A
MONTH AND THEN HOPEFULLY THE
CELLS HAVE ENOUGH OF THE NEW
BETA GLOBIN OR IN THIS CASE IT
GOES OFF IN A DIFFERENT
DIRECTION THAT MAKES IT ANT
ANTI, THEN HOPEFULLY IT WILL FIX
THE DISEASE THE PROTOCOL EVOLVED
OVER TIME AS A RESULT SUCCESS IN
THE FIRST COHORT WE NEED BETTER
TRANSDUCTION EFFICIENCY.
NOW BEING PUBLISHED BUT WHAT WE
FOUND IN CONTRAST WITH THE
NONHUMAN PRIMATE SICKLE-CELL
DISEASE HAS A MUCH HIGHER
FRACTION OF INFORMATION AND
CONTAMINATION MARKERS WHICH MADE
US THINK THE CD34 WE WERE
RELYING ON THAT IS A MARKER FOR
THAT BUT THEY ARE JUST BARELY
EXPRESSING CD34.
WITH A NUMBER OF STUDIES THAT IS
A WAY TO GET THESE AND THAT
CAUSE IS CATASTROPHIC OBLIGATION
BUT THEN WE GET REALLY GOOD
MOBILIZATION INTO THE BLOOD AND
WE GET THEM AT MUCH HIGHER
NUMBERS SO YOU CAN SEE ON THE
RIGHT ONLY ABOUT HALF MOBILIZE
LIKE 95 PERCENT.
NOT ONLY MORE BUT BETTER AND WE
GOT THEM WITH FEWER GRADE 3 OR
HIGHER.
WE IMPROVED TRANSDUCTION THROUGH
A BUNCH OF DIFFERENT THINGS INTO
THE MIX UNTIL WE COULD GET MORE
THAN 90 PERCENT ACROSS THE BOARD
AND THESE ARE THE RESULTS OF
THOSE EFFORTS.
GROUP A 0.1 SO 10 PERCENT HAVE 1
COPY.
THAT'S NOT ENOUGH TO PROVE NOT
TO BE ENOUGH SO THERE WAS SOME
IMPROVEMENT BUT NOT THE
20 PERCENT IT IS 10 PERCENT BUT
IN GROUP C THE NUMBER WAS ABOUT
1.5 SO THAT IS 150 PERCENT AND
WE HAVE MUCH HIGHER NUMBER SO
20000 AS THE MEDIAN IN GROUP C.
AND WE HAVE UPDATED THE RESULTS
SUBMITTED TO THE FDA IN THIS
TRIAL AND A FOLLOW-ON TRIAL WITH
59 SUBJECTS OVER 3 YEARS WITH
THE FOLLOW-UP IN HERE YOU CAN
SEE THE HEMOGLOBIN'S THE
BASELINE WAS 8 HEMOGLOBIN IS
ABOUT 12 OR 13 AND YOU CAN SEE
EVEN AS EARLY AS MONTH 3 WE HAVE
AN IMPROVEMENT OF IT NORMALIZES
AND THAT IS VECTOR DRIVEN AND IT
IS NEARLY HALF IT LOOKS LIKE A
SICKLE CELL TRAIT NOW.
AND THE RESULTS OF THE
ENUMERATION OF PAIN EVENTS AND
PAIN THAT IS SO SEVERE THE
PATIENT HAS TO GO TO THE
HOSPITAL AND GET IV NARCOTICS
AND THEN ON THE LEFT YOU CAN SEE
THE NUMBER OF TIMES THE 2 YEARS
PRIOR THEY HAD TO GO WIN TO BE
ADMITTED FOR IV NARCOTICS AND
WITH THE RED DOTS ON THE RIGHT
YOU CAN SEE AFTER SO 94 PERCENT
OF THE PATIENTS HAVE COMPLETE
RESOLUTION THERE NO LONGER
COMING TO THE HOSPITAL THROUGH
THE INTERVENTION AND THEN THE
FDA CONVINCED US TO MAKE THIS
THE PRIMARY ENDPOINT WE WERE
RETICENT AT FIRST BECAUSE PAIN
IS SUBJECTIVE AND IT IS
DIFFICULT BUT IT GOT BETTER AND
THE TOXICITIES THAT WE SAW WE
GET THE NEUTROPHIL DOWN AND
INFECTIONS AND SORES IN THEIR
MOUTH BUT THE SPECIFIC PROBLEMS
WE WERE LOOKING FOR BEING THE
INCLUSIVE DISEASE WE DID NOT SEE
DEATH RELATED COMPLICATIONS LIKE
MUTAGENESIS AND THERE WAS 1
UNFORTUNATE DEATH OF A PATIENT
WHO WAS WELL AFTER TRANSPLANT
BUT HAD PRE-EXISTING CARDIAC
DISEASE THAT WAS NOT REVERSED
WITH THIS INTERVENTION AND HAD
SUDDEN DEATH.
THIS WAS APPROVED.
MANY OF YOU ARE FAMILIAR WITH
THIS PUBLICATION DRIVEN WITH A
PRIOR NIH DIRECTOR THE FIRST OF
THE HUMAN GENOME AND IT GAVE US
OPPORTUNITIES TO START LOOKING
FOR OTHER THINGS WE CAN DO WHAT
ABOUT OTHER TARGETS?
SO MY COLLEAGUE AT KINGS COLLEGE
DID A STUDY WHEN THE GENOME WAS
PUBLISHED LOOKING FOR WHAT
AFFECTS FETAL HEMOGLOBIN
PERSISTENCE AND SOME CONTINUE
THROUGHOUT ADULT LIFE.
THEY DON'T SWITCH IT OFF AT
BIRTH.
THAT CAN PREVENT SICKLE OF THE
CELLS.
AND SHE FOUND THIS AND BLOOD
DONORS IN THE GENE PC 11 A SO
WE ASKED THE QUESTION CAN WE
INHIBIT THE GENE OR CUT THE
ENHANCER TO REACTIVATE FETAL
HEMOGLOBIN AS A WAY TO TREAT THE
DISEASE?
SO NOW YOU CAN SEE THE WORK THAT
YOU CAN CUT THE GENE AND GET THE
LEVELS OF FETAL HEMOGLOBIN IN
VITRO.
WE HAVE STUDIED THIS WITH THE
NONHUMAN PRIMATE AND THEN THESE
WERE CUT BECAUSE HE WANTED THIS
TO BE ERYTHROID SPECIFIC SO WE
DO A COMPETITIVE REPOPULATION
AND THEN THE OTHER HALF AND THEN
THAT IS PRESERVED WITH GOOD
RECONSTITUTION AND EQUAL
CONTRIBUTION AND ROBUST
REACTIVATION.
AND THEN TO PUT TOGETHER A
CLINICAL TRIAL THESE ARE THE
FIRST TO PATIENTS WHO HAS NEARLY
ALL FETAL HEMOGLOBIN NO MORE
TRANSFUSIONS AND THEN NEED THOSE
TO SURVIVE AND THEN TO SEE A
SICKLE-CELL PATIENT WHO NOW HAS
HALF OF THEIR HEMOGLOBIN COMING
FROM NORMALIZATION THIS IS NOW
PUBLISHED YOU CAN SEE FROM THE
BLUEBIRD STUDY ALMOST NO PAIN
EVENTS SO NOW THIS HAS ALSO BEEN
FDA APPROVED DECEMBER LAST
YEAR.
AND ACE SHOW YOU THAT THE PAIN
BEFORE AND AFTER SO YOU CAN HAVE
A COMPARATOR THERE ARE LOTS OF
PATIENTS THAT THE PAIN
PERSISTS.
WE CANNOT WORK WITH THE BONES
MOSTLY IN THE FIRST YEAR THEY
WILL HAVE PAIN BUT SOME AND READ
IN THE SECOND YEAR THOSE TAUGHT
PATIENTS REJECTED THE GRAPH
SWEAT OF 160 WAS VERY SIMILAR SO
THE GENE THERAPY APPROACHES
APPROXIMATE WHAT WE ARE DOING
WHEN WE COMPLETELY REPLACE THE
BONE MARROW SOMEBODY ELSE BUT WE
STILL NEED TO MAKE THIS WORK BUT
I WILL SHOW YOU SOME THINGS WE
HAVE BEEN TRYING TO DO WE HAVE
MADE ALL OF THE STRIDES USING
THE POISONS WE HAVE FOR MANY
DECADES SO WE HAVE THE BEDSIDE
AWARD WITH HARVARD STEMM CELL
INSTITUTE TO DEVELOP ANTIBODY
CONDITIONING IF WE CAN MAKE AN
ANTIBODY CONJUGATED DRUG AND
LEAVE EVERYTHING ELSE INTACT AND
NOT WITH THE TOXICITY AND IT IS
GREAT BECAUSE A LETTER FOR
GENITIVE CELLS THAT COULD
RAPIDLY INTERNALIZE WHEN IT
WOULD SHOW IN A MASS MODEL TO
DEPLETE THE BONE MARROW
COMPARTMENT AND GET A FULL GRAPH
WITH THE SINGLE DOSE WE DID THE
SAME THING AND NONHUMAN PRIMATE
MODEL USING A VECTOR AND WE GOT
THE EQUIVALENT AMONG GRANULAR
SITES WITH THE ANTIBODY TREATED
ANIMALS THE SAME THING WE USE IN
THE CLINIC AND 1 THING THAT WAS
VERY IMPORTANT THAT THE FEMALE
RECIPIENTS CONTINUE TO
DEMONSTRATE EVERY 20 DAYS AND
THAT SOMETHING WE HAD NEVER SEEN
WITH CONDITIONING OR WITH TOTAL
BODY RADIATION AND IN FACT, WE
SENT THESE ANIMALS TO A BREEDING
FACILITY DURING THE FIRST
BREEDING SEASON ACTUALLY 1 OF
THE PAIRED UP COUPLES WAS A MALE
AND A FEMALE SO THEY PROBABLY
MET IN THE ICU ALL OF THE CELLS
THAT IS EXPRESSED.
THAT WOULD BE USED TRYING TO DO
A BONE MARROW TRANSPLANT TRYING
TO GET RID OF IMMUNE CELLS SO WE
TESTED THAT AND IN THIS CASE WE
TESTED CRISPER EDITING BOTH AT
THE SPECIFIC ENHANCER SITE AND
THE SECOND SITE THAT CAN
REACTIVATE THEN WE GET BETTER
FETAL HEMOGLOBIN AND THEN TO SEE
60 PERCENT FETAL HEMOGLOBIN AS
COMPARED TO 30 PERCENT.
WHEN WE DO THAT AND THE LARGE
ANIMALS WE GET REALLY ROBUST
FETAL HEMOGLOBIN IN REACTIVATION
HIGHER IN THE TOP RIGHT AND THEN
HERE WAS CELLS.
SO IT IS ABOUT 90 PERCENT AND
USING THE ANTIBODY WAS SIMILAR
LEVELS AND WAS IN THE DUNBAR WE
DID CLONAL TRACKING WITH THE
SEQUENCE AND TO VIRAL VECTOR PUT
THOSE INTO STEMM CELLS AND WORD
GRAFT THEM AND THEN RETRIEVE
THOSE GRAFTED CELLS THE BARCODES
AND WE CAN TRACK ALL OF THE
PROGENY AND THEN TO HAVE A
REALLY ROBUST POPULATION WE WANT
TO MATCH OF TOTAL BODY RADIATION
AND YOU CAN SEE THE LINES ARE
OVERLAPPING FOR THEIR DIVERSITY
INDEX.
I WILL STOP HERE AND SUMMARIZE
WE CAN DO THIS NOW.
GENE EDITING WE HAVE TOXICITIES
AND WE THINK WE HAVE OVERCOME
SOME OF THAT BUT THE COMPANY
AGENDA DID NOT KEEP THE FUNDING
AND ASSETS HAVE BEEN MOVED
ELSEWHERE.
'S WE ARE HOPING SOMEBODY WILL
CONTINUE TO BRING THAT TO THE
CLINIC.
I DID NOT GET A CHANCE TO SHOW
DATA WE ARE NOW TRYING TO FIGURE
OUT HOW TO DO THIS IN VIVO WE
CAN MAKE ANTIBODIES TO KNOCK OUT
THE BONE MARROW BY CONJUGATING
DRUGS BUT NOW WE ARE WORKING ON
VIRAL VECTORS OR LIPID
NANOPARTICLES TO DIRECT THE
ADDITION OF A GENE SO THE DREAM
WOULD BE TO HAVE A PATIENT COME
TO THE CLINIC AND GIVE THEM THE
EQUIVALENT OF THE LISTED NANO
PARTICLE WITH RNA THROUGH IV TO
ADAPT.
IT SOUNDS EASY.
BUT IT HAS NOT BEEN WE HAVE BEEN
AT 1 IN A MILLION BEFORE SO WE
WILL CARRY ON AND SEE IF WE CAN
BRING THAT TO FRUITION.
THANK YOU TO THE CREW HERE THE
FIRST PATIENT ON THE GENE TRIAL.
>> WE ALSO HAVE TIME FOR
QUESTIONS IN THE ROOM.
THERE ARE 2 MICROPHONES.
YOU CAN APPROACH.
I DID NOT EXPECT THIS TALK BUT I
LOVE THE HISTORY LESSON.
I ALWAYS ENJOY TO SEE THAT AT
THE TAIL END OF A THERAPY.
1 OF THE THINGS TO HAVE SEVERAL
SERIES OF DESIGN GOALS
ULTIMATELY IT WAS 20 PERCENT AND
ALL THE OTHER THINGS THAT THROW
YOU OFF.
I AM CURIOUS HOW YOU KEPT A TEAM
ON BOARD AND DROPPING OUT WHEN
THE TARGETS WERE NOT MET AND ON
THE CLINICAL SIDE?
>> FOR A WHILE IT WAS TOUGH WE
HAD A COUPLE OF BIG HICCUPS IN
THE FIELD WE HAD A DEATH FROM A
VECTOR.
WHICH HAD IT WAS A KID REALLY
THINK ABOUT THEIR COMMITMENT TO
GENE THERAPY NOW WE'VE HAD
SOMETHING VERY BAD HAPPENED A
LOT OF PEOPLE BAILED AT THAT
TIME.
AND AS I SAID THE VIRAL VECTORS
MAKE YOU GO THROUGH A CYCLE AND
IT MAKES IT HARD BUT WE TRY TO
PRIDE OURSELVES ON BEING
BRICKLAYERS.
SO 1 BRICK AT A TIME BECAUSE
EVENTUALLY YOU STAND BACK AND
SAY IT WAS 1 BRICK AT A TIME BUT
WE WATCHED IT HAPPEN AS WE WATCH
IT OURSELVES.
WE HAD TO KEEP THE GOAL IN MIND
TO CURE THE DISEASE.
GOT A LOT OF ENTHUSIASM WITH THE
TRANSPLANT APPROACH THAT
HAPPENED EARLIER TO GO TO THE
CLINIC AND FEEL GOOD ABOUT WHAT
WE ARE DOING AND THEN GO BACK TO
THE LAB AND GO THROUGH SO THOSE
INCREMENTAL STEPS IS WHERE WE
HAVE GOTTEN.
>> TULANE UNIVERSITY.
YOU MENTIONED, I'M SORRY
EXCELLENT TALK BY THE WAY.
BUT YOU MENTIONED WITH THE
TRANSPLANTATION WITH THE GENE
EDITING TECHNOLOGY YOU KNOW YOU
SEEN TRIALS THROUGH POPULATIONS
SO WITH THE PATHOLOGY IT WORSENS
WITH AGE IS THERE ANY
CORRELATION WITH THE DAMAGE THAT
HAS BEEN DONE TO AFFECT
TRANSPLANTATION OUTCOMES AND
SUCCESS?
>> ESPECIALLY GENE THERAPY.
THE FIRST SUCCESS WAS A PATIENT
IN HIS TWENTIES WHO IS BEEN
TRANSFUSED ALL OF HIS LIFE FOR
QUITE DON'T THINK WE DO ENOUGH
OF THAT.
HIS BONE MARROW DID NOT LOOK
LIKE ANYBODY ELSE'S BUT
COMPLETELY NORMAL.
IT WORKED FOR HIM SO YOUNGER OR
WELL CARED FOR PATIENTS WITH
SICKLE CELL DISEASE HAVE LESS
DAMAGE THAT GENE THERAPY NOW
THOSE DOWN TO AGE 12.
I THINK THAT IS APPROPRIATE
BECAUSE MOST KIDS IF MANAGED
PROPERLY AT LEAST THROUGH AGE 12
ARE MANAGED PROPERLY THEY DON'T
HAVE A LOT OF TROUBLE IT IS A
DIFFERENT STORY FOR STROKE AND
THAT IS WHAT WE'RE ARGUING ABOUT
IN THE FIELD.
I'VE TRIED TO HAVE STROKE AS THE
INCLUSION BUT MOST OF THE
COMPANIES HAVE BEEN RELUCTANT
BECAUSE OF THE FEAR OF A
CATASTROPHIC EVENT BUT YOUNGER
IS BETTER THAN MICROENVIRONMENT
IS DAMAGED OVER TIME AND
ESPECIALLY ADULTS HAVE A LOT OF
PAIN INCIDENTS THEY ARE COMING
BACK AND FORTH TO THE ER.
THEY ARE NOT DRUG-SEEKING BUT
THEY ARE IN PAIN WITH A MUCH
HIGHER DEGREE OF ORGAN DAMAGE
AND HAVE A HARD TIME GETTING
THOSE STEMM CELLS.
>> I'M FROM UNIFORM SERVICES
ACROSS THE STREET YOU MENTIONED
AT THE BEGINNING OF THE TALK 30
YEARS OF RESEARCH COMPRESSED
INTO A 45 MINUTE TALK AND THAT
YOU ARE JUST MENTIONING THINK SO
DO YOU HAVE ADVICE TO OTHER
RESEARCHERS?
HOW DO YOU DEAL WITH FAILURE OR
THINGS THAT DON'T WORK ALONG THE
WAY DESPITE THE ROADBLOCKS?
>> MOST OF US ARE LOOKING FOR
THE BIG SCIENCE PAPER.
THAT'S NOT REALLY HOW IT GOES.
OVER TIME YOU GET A COUPLE OF
THOSE BIG DAYS BUT MOST OF THE
TIME WE ARE DOING BRICKLAYING
WAS SO SET YOUR GOALS TO
SOMETHING YOU KNOW YOU CAN
ACHIEVE AND HAVING THAT GOAL BE
A MEANINGFUL STEP WHY IS BONE
MARROW NOT WORKING?
LET'S DO THE THINGS TO
UNDERSTAND WHAT THAT LIMITATION
IS THAT IS A FEW BRICKS BUT THAT
1 LITTLE PIECE THAT YOU CAN MAKE
A MEANINGFUL CONTRIBUTION IT
WILL NOT LINEUP BUT THAT IS OKAY
EVENTUALLY YOU HAVE THESE BIG
DISCOVERIES BUT FOR THE MOST
PART IT IS THE BRICKLAYING SO
IT'S MORE AWARE OF THAT THAN
MOST.
>> THANK YOU VERY MUCH.
JUST SOME HOUSEKEEPING WITH THE
FIRST BREAK OF THE DAY THE
MORNING POSTERS HAVE BEEN SET UP
IF YOU HAVE QUESTIONS STOP BY
THE REGISTRATION DESK.
ALSO SCHEDULING A PROGRAM
DIRECTOR MEETING.
THEY CAN DIRECT YOU.
WE WILL TAKE A SMALL BREAK I
WILL SEE YOU BACK AT 10:45 A.M.
IN THIS ROOM.
SO WITH A COUPLE OF WITH THE
BASIC APPROACH AND IS QUITE
TRANSPARENT TO HAVE 2 VERSIONS
OF THAT WITH A DEEP BREATH YOUR
RIB CAGE IS FLEXIBLE ALSO TO
HAVE THE BASIC NEGATIVE PRESSURE
THAT COMES FROM THE DIAPHRAGM
WAS SPONTANEOUS BREATHING AS
OPPOSED TO MECHANICAL
RESPIRATION AND THESE ARE SOME
EXAMPLES OF NONFUNCTIONING BUT
IN THE LEFT YOU CAN SEE IT IS
FLEXIBLE AND THEN TO STUDY
DEEPLY AS WELL AS EXERCISE AND
THEN YOU CAN SEE THE MECHANICAL
VENTILATION AND THE POSITIVE
PRESSURE AND THEN THE NEGATIVE
PRESSURE COMES FROM THE BACK AS
IT OPENS TO THE AIR AND THEN IS
SPONTANEOUS BREATHING.
SO AS I SAID THESE ARE SOME OF
THE EXAMPLES IN THIS IS
BASICALLY 10 TIMES SO THAT YOU
CAN ZOOM IN AND SEE THE IMAGE.
SO THEN YOU CAN ZOOM IN AND HAVE
ACCESS AND CHANGE THE PRESSURE
AND TRACK THE SAME ALVEOLI.
THEY HAVE THIS PRESSURE BUT NOW
THEY CAN HAVE IT FOR THE
INDIVIDUAL EACH.HERE IS 1
SINGULAR.
SO COMING FROM A CANCER
BACKGROUND LOOKING AT HOW THE
TUMOR WOULD BE WITH A VIEW LIGHT
AND THEN YOU CAN ZOOM IN TO SEE
THAT METASTASIS IS THE LONG AND
CANCER CELLS HAVE A COUPLE OF AV
ALIVE.
AND THEN TO SEE HOW IT CHANGES
IN SIZE AND FUNCTION AND INSIDE
THE TUMOR IS NOT FUNCTIONING AT
ALL AND IT IS NOT AS FUNCTIONAL.
SO THEY ARE BOTH SIMILAR SIZE
AND THEN IF YOU STUDY EVEN
INSIDE THE TUMOR ARE FUNCTIONAL
SO THE CANCER CELLS HAVE NOT
MODELED AT ALL SO IT'S NOT ONLY
THE SIZE THE GROWTH PATTERN IS
IMPORTANT THE TUMOR GROWS LIKE
BALL AND THEN IT WOULD DISRUPT
THE SURROUNDING ENVIRONMENT SOME
PEOPLE CALL IT COOPERATIVE SO
WHAT IS THE LINK BETWEEN THE
STRUCTURE AND THE FUNCTION?
AND THEN WITH THE COLLEGE AND
AGAIN YOU CAN SEE THE METRICS
THE TUMOR IS DISRUPTING THE CELL
SO YOU CAN SEE THE MARGINAL
TUMOR AS THEY GROW THEY MAKE THE
COLLEGE AND STRETCHED AND IN
CONTRAST AND THE COLLEGE AND IS
UNTOUCHED.
SO WHAT ABOUT THE CAPILLARY
EFFECT?
IF THEY ARE AFFECTED HOW DO
TUMOR CELLS AFFECT CAPILLARY
FUNCTION?
HERE YOU CAN SEE THE WHOLE
OREGON AND THEN YOU CAN SEE THE
CAPILLARY IN THAT FLASH IS WHAT
COMES AND GOES AND HERE YOU CAN
SEE THAT THE SINGLE CAPILLARY
FUNCTION YOU CAN SEE THE TUMOR
AND THAT IT LEAVES OUT THE TUMOR
WITH SOME CAPILLARIES AROUND THE
TUMOR AT MODELS THE CAPILLARY
BUT ALSO AROUND THE TUMOR WAS
SOME ALVEOLI.
WE CAN QUANTIFY ALL OF THIS
THROUGH THE DETAILS BUT IF THE
CAPILLARIES ARE NOT FUNCTIONAL
THEN THE NUTRIENTS IN THE BLOOD
WILL GET TO THE TUMOR IF YOU
WAIT LONG ENOUGH THEN DIFFUSION
IS A PROCESS YOU CAN SEE
BASICALLY YOU CAN CALCULATE THE
COEFFICIENT INSIDE THE SUPER
TRAINEE TUMORS IN THE
ENVIRONMENT.
SO WE HAVE A LOT OF INTEREST IN
THE TUMOR.
SO HERE YOU COULD LABEL INTACT
THE RESIDENT T CELLS THEY ARE
POSITIVE AND THEN THE BLUE
BASICALLY IS SOME A STATIC
TUMORS AND HERE YOU CAN SEE HOW
THE T CELLS MOVE MOST OF THE
TIME THEY INFILTRATE THE TUMOR
WE KNOW FROM HISTOLOGY BUT IT IS
A SNAPSHOT IN HERE YOU CAN SEE
HOW THEY MOVE AROUND THOSE T
CELLS AT THE MARGIN ARE MUCH
FASTER THAN GOING AWAY FROM THE
TUMOR AND THEN YOU CAN SEE WE
DON'T KNOW EXACTLY ARE THEY
EXHAUSTED OR RECOGNIZING YOU
DON'T EVEN KNOW THERE ARE
STATIONARY CELLS SO WITH THAT
PROCESS OF UNDERSTANDING THOSE
IF YOU WAIT LONG ENOUGH YOU CAN
SEE CANCER CELLS SURROUNDED BY
THE POSITIVE T CELLS.
YOU HAVE ACCESS TO CARCINOGEN
USE WITH LONG TUMORS AS WELL.
YOU CAN LABEL ALL THE CELLS AND
THEN YOU CAN ALSO VISUALIZE IT.
SINCE WE HAVE A LOT OF CONTROL
YOU CAN CHANGE THE BLOOD
PRESSURE OR AIR PRESSURE AND
HERE WE CHANGE THE BLOOD
PRESSURE WE SAW THE NEUTROPHIL
MOVE A LOT FASTER AT HIGHER
PRESSURE.
IF YOU DO THIS EXPERIMENT OF
CHANGING THE PRESSURE YOU DON'T
SEE THE CHANGE BUT HERE YOU CAN
SEE HOW THE NEUTROPHIL AS IT
INCREASES BASICALLY THE BLOOD
PRESSURE AND THEN THAT GOD'S
INTO THE AV ALIVE IT DOESN'T
CHANGE BY PRESSURE.
WE DON'T KNOW THE MECHANISM BUT
WE KNOW THAT AS SOON AS YOU
REDUCE THE PRESSURE IT GOES DOWN
AND THINK IT HAS SOMETHING TO DO
WITH VASCULAR DISTINCTION THE
STRETCHING MAY COMMUNICATE THIS
CAUSING AN INCREASE OF THE
SPEEDS I TOLD YOU VERY BRIEFLY
ABOUT THE SOLID IN THE LIQUID
PHASE BUT WHAT ABOUT AIR?
WE CONTINUALLY BREEZE
MICROSCOPIC PARTICLES AND
IRONICALLY EVEN THOUGH THEY ARE
MICROSCOPIC PEOPLE DON'T USE IT
TO STUDY PARTICLES BECAUSE YOU
THINK WE SOLVE THE PROBLEM SO AS
I SAID WE CAN VENTILATE BY
NEGATIVE PRESSURE YOU CAN ATTACH
A NEBULIZER THIS IS A LITTLE
DISTORTED BUT THE NEBULIZER AND
THE LONG.
YOU CAN SEE A SINGLE DROP OF - -
A SINGLE DROPLET WE CAN SEE A
GREEN DOT THAT IS A SINGLE
DROPLET IN THE AIR PHASE AND
HERE BASICALLY YOU CAN TRACK
SOMEHOW THE VIDEO IS NOT RUNNING
BUT YOU CAN TRACK THE PARTICLE
BEFORE DEPOSITS ON THE SURFACE
OF THE AV ALIVE.
SO TO VISUALIZE AND HERE YOU
SELL TO TRACK THE PARTICLES
WHICH COULD BE ANYTHING NOW WE
HAVE A HOLD OF YOU AND WE SEE A
BEAUTIFUL PATTERN OF
HETEROGENEITY IT WAS VERY
SIMILAR TO ABANDON YOU CAN SEE
BASICALLY WITH THE AV ALLY AND
THEN IT IS ALSO HAPPENING FOR
MANY DIFFERENT TYPES OF
NANOPARTICLES OR A PATHOGEN OR
E. COLI.
OR IF IT IS A SURFACTANT YOU CAN
SEE THE MOSAIC PATTERN.
THEN THE QUESTION IS FOR SOMEONE
WHY?
WHAT IS THE CAUSE FOR THAT?
AND WHAT ARE THE CONSEQUENCES?
SO WE SEE THE PATTERN HAPPENS
ALL THE WAY UP BASICALLY IT
CHANGES AND EVOLVES IT'S NOT THE
SAME BUT THE HETEROGENEITY IS
THERE AND BY THE WAY THEY ARE
ALSO DOING THIS ON THE HUMAN
LONG SO IT'S A LARGE ANIMAL NOT
ONLY THE MOUSE BUT IF IT
EXPERIENCES THIS OVER THE
LIFETIME SOME GET THE PATHOGEN
AND SOME DOUBT THEY COULD BE
DIFFERENT AND THEN THAT
DIFFERENCE AFFECTS THE
METASTASES AND I CANCER CELLS SO
THE HETEROGENEITY THAT WAS THERE
IT WAS BECAUSE TO VISUALIZE AND
THEN TO DISCOVER THE
HETEROGENEITY AND WE ARE EXCITED
ABOUT THE CAUSES AND THE
CONSEQUENCES.
SO FAR I TALKED ABOUT THE CASES
AND BASICALLY THE DETAILS ARE IN
THE PUBLICATION BUT I WILL TELL
YOU ABOUT ONGOING SO SO FAR IT'S
NOT BLOOD SO WE DECIDE TO SEND
THE BLOOD AND THE BEST WAY IS TO
USE FRESH BLOOD.
I KNOW IT SOUNDS CRAZY BUT IF I
COULD THEN WE COULD DO A LOT'S
WE WERE VERY EXCITED AND
BASICALLY HAVING TRACTION IN THE
MOUTH AND IN THE LONG THEY COULD
SEE THE EFFECT OF THE YOUNGBLOOD
AND THEN JUST TO SHOW YOU WE
HAVE DONE IT.
THIS IS THE MOUSE THAT IS
WALKING AND YOU CAN SEE THERE
THAT THE BLOOD IS CONNECTED TO
THIS LUNG AND IT IS CONTINUOUSLY
GOING THERE.
YOU CAN SEE THE BLOOD CELLS
GOING THROUGH THE CIRCULATION
AND YOU CAN MONITOR AND
REAL-TIME.
AND THEN WE CAN COUNT THE NUMBER
OF CELLS GOING INTO THE LUNG SO
THAT BASICALLY YOU CAN DO THIS
WITH REAL BLOOD SO I WILL SKIP
ALL OF THIS IF YOU WANT TO SCALE
IT UP AND START AND I KNOW THAT
SO BASICALLY TO HAVE THE BRAIN
STUDIED OUTSIDE OF THE BODY.
[LAUGHTER]
THANK YOU TO THE TEAM AND MY
FUNDING SOURCES.
THANK YOU SO MUCH.
[APPLAUSE]
>> THE MICROPHONES ARE OPEN FOR
QUESTIONS.
WE HAVE TIME FOR 1 OR 2
QUESTIONS.
>> A BEAUTIFUL TALK.
THE DYNAMICS THAT YOU SHOW DUE
TO PRESSURE, DOES IT DEPEND ON
THE PRESSURE FLUCTUATION OR IF
YOU KEEP THE PRESSURE CONSTANT
DOES IT GO BACK TO STATIONARY?
>> AT THIS TIME WE KEPT THE
PRESSURE CONSTANT INSTEAD OF
FLUCTUATING.
>> NE MECHANISM?
>> AS I SAID WE DON'T KNOW
EXACTLY BUT WE INCREASE THE
PRESSURE AND THE CAPILLARY
INCREASE WE THINK MAY BE THE
CELLS HAVE BEEN STRETCHED THAT
IS OUR HYPOTHESIS.
>> A QUICK TECHNICAL QUESTION
LOOKING AT THE ISCHEMIA ON AND
DISSECTION OF HOW LONG IT TAKES
FOR YOU BASICALLY TO GET IT INTO
THAT PROFUSE SET UP AND YOU SEE
THE TEMPORAL EFFECT?
>> THAT'S A GOOD QUESTION I AM
WORRIED OF ALL THE EFFECTS ON
THE LUNGS.
I AM PUSHING MY STUDENTS TO DO
THIS QUICKLY.
WE GOT THIS TO ALMOST CONTINUOUS
AS SOON AS YOU CUT OUT THE
CIRCULATION YOU CAN PUT IN THE
NEW CIRCULATION.
I WOULD SAY WITHIN A MINUTE OR
2.
>> GREAT WORK.
I'M TRYING TO FIGURE OUT FOR THE
CANCER MODEL WHAT PATIENT
VERSION DOES THAT REPRESENT?
HAVE YOU DONE ANOTHER STRAIN SO
IT REPRESENTS THE HETEROGENEITY
OF HOW IT PRESENTS IN DIFFERENT
PATIENTS?
I THINK THAT IS AN IMPORTANT
PART.
>> IT DEFINITELY.
I GUESS YOU ARE TALKING ABOUT
THE PATIENTS THAT DON'T RESPOND
TO THERAPY BECAUSE THE CANCER
CELLS OVERRIDE THE STRUCTURE SO
THEY HAVE THE SIMILAR DATA
POPULATION SO I STARTED THE
TOPIC IN THE BRAIN VERY
DIFFUSIVE 80 PERCENT ARE
DIFFUSIVE AS OPPOSED TO THE
MARGINAL ONES.
AND TO BE EASILY DISSECTED BUT
HERE WE SAW THAT IN THE LUNG AS
IT WAS HAPPENING.
>> THANK YOU VERY MUCH.
[APPLAUSE]
HE WILL BE AROUND TO CHECK THEM
OUT AT THE BRAKES.
OUR NEXT SPEAKER WHO WAS BROUGHT
HERE TO START THE DATA CENTER
FOR BIOENGINEERING AND RELATED
PROJECTS ACTUALLY FROM THE
NATIONAL INSTITUTE OF AGING
ENACTED AFFILIATED WITH THE DATA
CENTER AND WE ARE GLAD SHE IS
HERE TO SHARE THIS WORK WITH YOU
ALL.
[APPLAUSE]
>> THANK YOU VERY MUCH AND THE
WHOLE TEAM FOR ORGANIZING THIS
WONDERFUL EVENT.
I THINK WE SHOULD HAVE MORE OF
THESE.
CONGRATULATIONS TO BRING THE
COMMUNITIES TOGETHER.
I HAVE A VERY SHORT TIME.
I WILL TRY TO BE VERY BRIEF THE
TITLE OF MY TALK SHOULD HAVE
BEEN LIVE IMAGING TO ACCESS THE
TIME DIMENSION OF ANY BIOLOGY.
SO I WOULD LIKE TO USE AS AN
EXAMPLE WE CAN DO IT BETTER WITH
QUANTITATIVE APPROACHES.
LET'S GET STARTED.
SO THERE IS A RECURRING THEME IN
CELL SIGNALING INVOLVING SIGNAL
RESPONSIVE FACTORS THAT CONTROL
MANY IMPORTANT DOWNSTREAM GENE
EXPRESSIONS.
FOR EXAMPLE THERE ARE ALL OF
THESE THINGS AND ESSENTIALLY
THEY DO THE SAME THING.
THEY KNOW HOW TO AUTO REGULATE
THEMSELVES SO THEY INDUCE THEIR
OWN NEGATIVE INHIBITORS SO THIS
IS AN INTERESTING SITUATION
THEORETICALLY BECAUSE THERE IS
TIME DELAY INVOLVED WITH PROTEIN
SYNTHESIS.
SO ALL OF THE SYSTEMS ARE
ESSENTIALLY NONLINEAR DYNAMIC
AND YOU CAN KNOW EVERYTHING
ABOUT THEIR BIOCHEMISTRY AND
STILL REALLY HAVE DIFFICULTY
PREDICTING HOW THEY WILL
BEHAVE.
SO I WOULD LIKE TO CONVINCE YOU
THAT UNDERSTANDING THEIR
ACTIVITY DYNAMICS CAN REALLY
TELL US A LOT ABOUT HOW THEY
REGULATE BIOLOGY AND FOR THIS WE
NEED TO QUANTITATIVE SYSTEMS.
SO LET ME TALK NOW IT IS
PROBABLY IMPORTANT IN HUMAN
HEALTH BECAUSE IT BASICALLY
CONTROLS ALL OF THE CELL TYPES
IN THE IMMUNE SYSTEM IN RESPONSE
TO MANY CONDITIONS THEY
DIFFERENTIATE AND HAVE ANTIGENS
AND INTERACT WITH OTHER HUMAN
CELLS.
SO THE LAB HAS MADE THE
SCHEMATIC WHERE THE CAPILLARY IS
LIKE A GODFATHER FEATURE SO HOW
DOES THIS HAPPEN?
WHEN I CAPILLARY IS ACTIVATED IN
ALL OF THESE SITUATIONS?
WE CANNOT EXPLAIN WHAT IT DOES
BY SIMPLE ON AND OFF THERE HAS
TO BE MORE TO IT AND THE REAL
QUESTION IS HOW MUCH REGULATORY
INFORMATION MIGHT BE INCLUDED IN
THE RHYTHM OR THE TEMPORAL
DYNAMICS?
THERE HAS BEEN A LINE OF VERY
FASCINATING STUDIES OVER THE
YEARS.
BUT MOSTLY THEY HAVE USED
IMMORTALIZED TRANSFORM CELL
LINES SO WE REALLY CAN'T TELL A
LOT ABOUT WHAT THE PRIMARY CELLS
DO TO DO ALL OF THE WONDERFUL
RESPONSES ANOTHER DEFICIENCY IN
THE FIELD IS MOST OF THE WORK IS
ABOUT P 65 THAT THERE IS ANOTHER
VERY IMPORTANT UNIT AND WE KNOW
VERY LITTLE ABOUT WHAT IT DOES.
SO I WOULD LIKE TO POINT OUT ANY
DYNAMIC SECOND PLAY AN IMPORTANT
ROLE TO CONTROL THE SPATIAL
TEMPORAL EXPRESSION PATTERNS OF
DOWNSTREAM GENES AND MANY ARE
RECEPTORS IN THESE COULD BE VERY
IMPORTANT TO CONVEY THE
INFORMATION SENSED INITIALLY BY
THE SENDING CELL.
SO HOW DO YOU MEASURE THE
DYNAMICS AND THE LIVE CELLS AND
WHY DO WE NEED TO DO THIS IN
REAL TIME?
THE SHORT ANSWER IS IF YOU TAKE
TIME POINTS OF ANY SNAPSHOT THAT
FAILS TO CONVEY THE WHOLE
BIOLOGY BUT IN LIVE SALES
CONVENIENT PROXY IS HOW MUCH IS
IN THE NUCLEUS BECAUSE IT IS
BOUND BY THE PROTEINS MOST
IMPORTANTLY THE ALPHA FORM WHICH
IS ALSO A NEGATIVE FEEDBACK LOOP
BECAUSE UPSTREAM STIMULI CAN
CONVERGE AND THIS EVENT HAS A
DEGRADATION PROCESS SO ANY THAT
DISAPPEAR AND NOW THE CYTOPLASM
BACK CAN ACTIVATE THE GENES SO
THIS IS A DELAYED NEGATIVE
FEEDBACK GROUP RENDERING THE
SYSTEM COMPLEX SO LET ME SHOW
YOU A MOVIE PLAYED SIDE-BY-SIDE
OF HOW MUCH IS IN THE NUCLEUS
THE CELLS ARE ACTIVATED AND IT
KEEPS OSCILLATING AND LOOK AT
THE TIMESCALE YOU DON'T GET TO
SEE THIS UNTIL YOU FOLLOW THE
CELLS OVER HOURS AND HOURS WE
HAVE DONE THIS A WHILE AGO AND
FOUND THAT MOST ALL CELLS ARE
DOING THIS IT IS JUST THAT THEY
ARE SLIGHTLY OUT OF SYNC.
AND THEN THEY GO OUT OF PHASE
VERY QUICKLY.
WITHIN THE COMPLEX DYNAMIC
PATTERNS OCCUR BECAUSE WE AND
OTHERS HAVE SHOWN THIS IS VERY
IMPORTANT FOR TRANSCRIPTIONAL
OUTPUT OF THE TARGET GENE SO IF
WE FOLLOW THAT MANY TARGET
GENE, WE HAVE FOUND FOR
IMMEDIATE EARLY REPORTERS IT IS
THE AREA UNDER THE CURVE THIS IS
THE QUANTITY THAT IS BEST
CORRELATED SO HERE IS THE
EXAMPLE OF A CONTROL OF THE
TRANSCRIPTION OUTPUT BUT THE
TARGET GENES TO FIND TUNE THE
BEHAVIORS.
SO THIS WAS ALL ENGINEERED SO
NOW WE WILL'S SWITCHOVER TO
PRIMARY CELLS BECAUSE WHEN I
MOVED WE HAVE BEEN MAKING
REPORTER MOUSE LINES THOSE ARE
SUBUNITS IN MY PRIMARY CELLS.
HERE IS THE SET UP.
FIRST WE HAD TO DO WITH THE
TECHNICAL CHALLENGE BECAUSE THE
PROTEIN IS THE INDIGENOUS
PROTEIN AND LOW EXPRESS.
IT IS FAR BELOW THE NORMAL RANGE
OF WHAT WE ARE USED TO FROM CELL
BIOLOGY IMAGING.
WE HAVE TO DRASTICALLY FIND TUNE
AND REOPTIMIZE THE ACQUISITION
SETTINGS ESPECIALLY WITH 3
CHANNELS TO HAVE A SEPARATE
CHANNEL JUST TO SEGMENT THE
NUCLEAR BOUNDARIES WITH NUCLEAR
LABELS USING THE BENIGN DIE AND
IMAGE AND QUANTIFY THE DATA
ATTRACT THE CELLS WITH THE
DOWNSTREAM ANALYSIS.
SO IF YOU DO THAT YOU CAN ASK
ALL SORTS OF INTERESTING
QUESTIONS AND THE MACROPHAGE
SINCE MANY DIFFERENT MICROBIAL
PRODUCTS VIRUS TO BACTERIA AND
THESE ARE SPECIFIC TO RECEPTORS
AND THERE ARE SEVERAL THAT GIVE
A 1 : 1 RECOGNITION BUT INSIDE
THE CELLS THEY ALL CONVERGE TO
THE COMPLEX AND THEY ACTIVATE
AND A FEW OTHER FACTORS.
BUT ESSENTIALLY IT IS A PUZZLE
BECAUSE CAPILLARIES ACTIVATED
BUT YET SOMEHOW YOU HAVE TO
RESPOND APPROPRIATELY TO
DIFFERENT MICROBES IT IS AN
INFORMATION PROCESSING PROBLEM
THAT HAS TO BE CONVEYED INTO THE
CELLS.
SO THIS IS A PRETTY COMPLICATED
MODEL THAT SENDS THE INDIVIDUAL
AND WE GO THROUGH THE ADAPTER
MOLECULES AND COME EVENTUALLY TO
THE CORE SO IN COLLABORATION AT
UCLA WE FIND UPDATED
MATHEMATICAL MODEL AND AS YOU
KNOW THE MATHEMATICAL MODEL
CANNOT BE THE SAME AS THE REAL
THING BUT IT CAN BE VERY USEFUL
TO ASK QUESTIONS ABOUT UNTESTED
CONDITIONS JUST SO THAT WE FIX
THE SIMULATIONS TO THE SINGLE
CELL FROM LIVE CELL IMAGING BUT
JUST FOCUSING ON WHAT WE LEARN
FROM THE EXPERIMENTAL DATA.
HERE IS THE DATA FROM A BIRDS
EYE VIEW HERE IS A HEAT MAP
REPRESENTATION EACH ROW IS A
SINGLE CELL TRACE RESPONDING TO
LPS AND THESE ARE FROM THE BONE
MARROW MACROPHAGE AND THE FIRST
THING I NOTICED LOOKING AT THIS
DATA IS IT LOOKS VERY DIFFERENT
AND FIRST OF ALL WE DID NOT SEE
ANY RESPONSES AND THEN TO SHOW A
TEMPORAL TIME TRACE OF THE
SIGNALING DYNAMICS AS YOU CAN
SEE THEY WERE MORE FASTER AND
SHORTER LIVED THE PRIMARY CELL
BEHAVIOR WE ARE SEEING A LOT
STRONGER WITH VERY EXQUISITE
TIME THROUGH THE FIRST PEAK THIS
IS JUST THE VISUAL IMPRESSION
WHAT ABOUT THE QUANTIFIED
FEATURES?
SO NOW WE HAVE TIME SERIES FOR
HUNDREDS OF CELLS TO EXTRACT
SPECIFIC QUANTITATIVE FEATURES
WERE NOW THE TIME SERIES IS A
LONG AND COMPLICATED THING FOR
TIME ANALYSIS SO IT'S NICE TO
EXTRACT MEANINGFUL FEATURES TO
CORRELATE BETTER WE EXTRACTED
PEAK AMPLITUDE TIMING AND WITH
THE OSCILLATION AND THE
ATTENUATION RATE WE LOOK AT THE
FEATURES AND WE ASKED OUR THERE
INFORMATION CONTENT HERE IN
THESE FEATURES?
SO WE MATCH 28 DIMENSIONAL WITH
ONLY 1 SUBUNIT SPACE AND WITH
THE MACHINE LEARNING EXERCISE ON
70 PERCENT AND WE USE THE
REMAINING 30 PERCENT WITH THE
UNKNOWN LABEL.
SO WE DID TENFOLD ACROSS
VALIDATION AND HERE IS A
RESULT.
SO WHEN THE MODEL GOT THE
IDENTITY CORRECT BUT THIS IS
USED ONLY WITH THE 8 FEATURES.
SO THEN LOOK AT THE DIAGONAL
ACCURACY HOW GOOD IT IS EVEN IF
YOU ONLY USE THE 8 FEATURES OF
THE SIGNALING DYNAMICS.
THERE IS SOME IMPROVEMENT.
THAT IS INTERESTING.
SO NOW I WILL GO FAST.
SO THE BOTTOM LINE OF THE STUDY
IS THAT YES INDEED THE SIGNALING
DYNAMICS CONTAINS A LOT OF
INFORMATION ABOUT WHAT IT JUST
SAW.
IS IT CONFUSING OF A OR B OR C
NOW CAN ACCURATELY DISCRIMINATE
SO WE LEARNED EXACTLY HOW THE
FEATURES ARE CORRELATED AND BY
GIVING EXAMPLES OF OTHER PRIMARY
MACROPHAGE EXAMPLES.
AND NARROW INFORMATION IS A BIG
FOCUS AND LOOK AT MACROPHAGE IN
THE BRAIN.
THE ONLY RESIDENT IN THE CELLS
OF THE BRAIN.
BUT SOME DO NOT EVEN EXPRESSED 0
ONLY A SUBSET DO EXPRESS.
SO I WILL PLAY THE MOVIE AND YOU
WILL SEE TNF COMING IN AT TIME 0
BUT NOW GOING INTO THE NUCLEUS
WHEN ACTIVATED AND THEN TO SEE
THOSE ASYNCHRONOUS
NOTIFICATIONS.
WE DON'T HAVE TIME BUT WE
LEARNED A LOT HOW SIGNALING
WORKS WITH MICROGLIA AND SAW THE
INTERESTING DIFFERENCES FROM THE
YOUNG BRAIN NOW LOOKING AT
MICROGLIA FROM A MOUSE MODEL
FROM ALZHEIMER'S DISEASE AND
ANOTHER THING YOU CAN DO WITH
THIS INSTEAD OF LOOKING AT 2
DIFFERENT SUBUNITS YOU COULD
LOOK AT 1 SUBUNIT.
HERE WE LOOK AT GREEN LABEL DATA
I WILL PLAY THE MOVIE BUT
INITIALLY GRADUALLY YOU WILL SEE
SOME OF THE SOULS STICKING UP.
THIS IS BETTER DASH VERY
HETEROGENEOUS AND THEN YOU WILL
SEE THE BURST OF PHAGOCYTOSIS SO
IT IS INCREDIBLY VARIABLE SOME
DON'T EVEN TAKE UP MUCH UNTIL
THE END SO WE SEE ALL SORTS OF
BEHAVIORS AND WE ARE TRYING TO
SEE THE MARKERS OF THE
DIFFERENTIAL PHENOTYPES MIGHT BE
AND THIS IS THE WAY WE QUANTIFY
THE SAME SCALE DYNAMICS TO SAY
EXACTLY WHICH BEHAVIOR
CORRESPONDS TO WHICH SIGNALING
PATTERN ANOTHER EXAMPLE IS THE
ADAPTIVE SYSTEM NOW T CELLS ARE
KNOWN TO CLEANLY EXPAND AND
PROLIFERATE IN 2 OTHER RESPONSES
SO YOU HAVE TO FOLLOW THEM
THROUGH CELL DIVISION.
SO ALL SORTS OF COOL THINGS CAN
BE DONE IF YOU ARE FOLLOWING THE
PRIMARY CELLS BEHAVIOR AND
LOOKING AT THE BEHAVIOR.
LIKE TO THINK OUR CURRENT TEAM
MEMBERS AND FORMER MEMBERS WHO
ARE VERY IMPORTANT FOR THE WORK
I SHOWED YOU TODAY.
AND OUR COLLABORATORS.
VERY QUICKLY I WANT TO END SO
THANKFUL YOU HAVE THIS MEETING
PEOPLE ARE MORE AND MORE AND
ENGINEERING AND ARTIFICIAL
INTELLIGENCE AND BIOMEDICINE AND
WE REALLY NEED TO HAVE MORE
ACROSS INTERACTIONS TO LOWER THE
BOUNDARIES AND ALSO STEP OUT OF
OUR COMFORT ZONES AND DO MORE
THAN JUST BUSINESS AS USUAL IN
FOR THE FUNDING DECISION-MAKERS
WE NEED LONG-TERM FUNDING
BECAUSE THAT'S THE ONLY WAY TO
CROSS TRAIN THE NEXT GENERATION
OF SCIENTISTS.
COLLABORATION IS WORTH IT BUT IT
REQUIRES PATIENCE AND MUTUAL
RESPECT FOR ALL PARTICIPANTS.
YOU SO MUCH CAPS OFF.
>> WE HAVE OUR FINAL SPEAKER OF
THE MORNING OF INVITED TALKS
FROM THE UNIVERSITY OF NEVADA
RENO AND ALSO AS SHE GETS TO THE
Q&A PORTION RAPIDFIRE SPEAKERS
CAN COME UP.
>> THANK YOU SO MUCH FOR HAVING
ME AND THE OPPORTUNITY TO GIVE A
TALK I'M VERY EXCITED TO SHARE
THE RESEARCH WITH THE LIGHT
ACTIVATED PURCHASE SYSTEMS TO
CONTROL FOR THE ATTRACTIONS MY
LAB IS MAJORLY FOCUSED ON
ENGINEERING AND DESIGN AND I
WILL SHARE OUR ONGOING RESEARCH
AND HOW THIS LIGHT ACTIVATED
SYSTEM COMES TO PLAY BUT TO
START 1 OF THE MAIN ENZYMES THAT
IS IMPORTANT WITH HEALTH AND
DISEASE MY LAB IS INTERESTED IN
TARGETING AND THEY PLAY A KEY
ROLE OF THE MATRIX FOR MODELING
AND AS YOU CAN SEE IN THIS
CARTOON THEY DO HAVE A VERY
DIVERSE ROLE MULTI FUNCTIONAL
AND ECM IS JUST 1 SUBSTRATE AND
IT BECOMES VERY RELEVANT BUT
ALSO INVOLVED IN MANY DIFFERENT
TYPE OF CELLS SIGNALING PATHWAYS
AND THE NATURAL INHIBITORS AND
USUALLY IT IS EXPRESSED AS AN
INACTIVE FORM AND ACTIVATED WITH
CLEAVAGE AND THEN TO BE
REGULATED AS THE NATURAL
INHIBITORS AND THEN THIS GOES
OFF BALANCE IT COULD BE THE
SOURCE OF SEVERAL DISEASES FROM
HEAD TO TOE AND THIS IS JUST
BASICALLY SOME EXAMPLES TO BE
SPECIFIC MEMBERS THAT CAN BE
RESPONSIBLE OF SEVERAL DIFFERENT
TYPES OF CANCER, CHRONOLOGICAL
DISORDERS OR DIABETES SO I HOPE
WE CONVINCE YOU THAT THE
BROAD-SPECTRUM INHIBITORS HAVE
FAILED AND ARE NOT EFFECTIVE AS
POTENTIAL THERAPEUTICS AS THEY
HAVE KEY ROLES AND PHYSIOLOGICAL
FUNCTIONS AND KEY CELLULAR
FUNCTIONS.
MY LAB IS INTERESTED IN THE
ENGINEERING AND DESIGN TOOLS AND
THEN TO BE MORE SELECTIVE
SCAFFOLDS AND THEN JUST A VERY
BRIEF OVERVIEW OF WHAT WE HAVE
DONE SO FAR NOW LEADING MORE
EFFECTIVE PHOTO RELATED TOOLS
AND TECHNOLOGIES TO EXPAND THE
SYSTEM TO MAKE IT MORE EFFECT
EFFECTIVE.
IN THE PAST WE HAVE USED THIS
COMBINATION USING A PLATFORM TO
ENGINEER TO BE THE ULTRA BINDER
TO SPECIFIC CASES AND IF YOU
LOOK AT THE STRUCTURES TO FIND
OUT THE DOMAINS OF THE PROTEIN
WORKING TOGETHER BUT MORE
IMPORTANTLY ARE INTERESTED IN
SELECTIVE AND VENDORS NOT ONLY
WITH BETTER BINDERS BUT MORE
IMPORTANTLY THOSE THAT ARE
TARGETING 1 SPECIFIC ENZYME AND
NOT THE OTHERS AND BE VERY
SPECIFIC TO DO THAT TO BE MORE
EFFICIENT SO THEN WE HAVE USED A
COUNTER SELECTIVE STRATEGY WITH
THE UNLABELED COMPETITOR WHERE
IT WILL BASICALLY HELP US TO
ELIMINATE THE VALUES THAT ARE
NON- SELECTIVE BINDERS AS YOU
CAN SEE HERE A FEW OF THE
MUTANTS FOR MORE SPECIFIC AND
DISTINGUISH WITH THE POPULATION
SHOWN IN RED VERSUS VERY CLOSE
EXTERNALIZED FUNCTION AND THAT
WAS A GREAT SUCCESS KNOWING HOW
SIMILAR THEY ARE AND IT IS
IMPOSSIBLE TO ACHIEVE THAT
NATURALLY.
BUT MOVING FORWARD NOW WE ARE
INTERESTED IN KNOWING MORE ABOUT
BASICALLY THE SPECIFIC SCAFFOLDS
AND HOW WE CAN ENGINEER HOW WE
CAN HAVE A MODULAR SCAFFOLD TO
BIND AND ACHIEVE THAT USING DNA
SHUFFLING TECHNIQUES AND
SCREENING THROUGH EVOLUTION AND
FIND MINIMAL VARIANCE AS SHORT
AS 20 AMINO ACIDS FALLING INTO
PEPTIDE CATEGORY THAT CAN
EFFECTIVELY INHIBIT MMP SO THAT
HAS A LOT OF VALUE IN TERMS OF
NOT ONLY TO MODULAR PLAY AROUND
AND FINE TUNE BUT TISSUE
PENETRATION.
SO A LIMITED OVERVIEW HOW YOU
WERE USING THEM AND THE LIGHT
ACTIVATED SYSTEM IS NEEDED I
WOULD LIKE TO BRING OUT A BLOOD
BRAIN BARRIER AND THE IMPORTANCE
OF THIS RESEARCH AS YOU KNOW IT
IS MADE FROM THE CELLS AND
ATTACHED AND SPECIFIC MEMBERS OF
THIS ENZYME FAMILY THAT CAN
CAUSE PROBLEMS THEY ARE KNOWN TO
DEGRADE THOSE JUNCTIONS SO IN
THIS CASE OF THE CENTRAL NERVOUS
SYSTEM DISORDER AND MORE
IMPORTANTLY THE LEAKAGE CAN
CAUSE SEVERAL PROBLEMS 1 BEING
THE AGGREGATES INTO THE BRAIN
AND SO FORTH AND IN CASE OF
SEVERAL CANCERS YOU CAN IMAGINE
IT WOULD WORK THE OTHER WAY
AROUND IF INTEGRITY IS
COMPROMISED THAT THIS CAN HAPPEN
EITHER WAY WHICH IS NOT GOOD AND
WE DON'T LIKE IT.
SO SEVERAL MEMBERS OF THE FAMILY
HAS BEEN KNOWN TO COMPROMISE THE
INTEGRITY -- -- INTEGRITY IF NOT
REGULATED SO WE WOULD LIKE TO
COME TO UNDERSTAND THIS
PHENOMENON AS FINE-TUNING THEIR
PROBES AND MOLECULES TO MORE
EFFECTIVELY TARGET THAT AND NOT
ONLY PROTECT THE INTEGRITY BUT
THE TRANSPORT PHENOMENON AND
POTENTIALLY HAVE MOLECULES THAT
CAN ALSO TRANSPORT SO 2
CONTRADICTORY CONCEPTS.
THAT BEING SAID STARTED WORKING
ON IN VITRO ASSAYS BY GROWING
THE CELLS ON THE FILTERS SO YOU
CAN DETECT THE FORMATION BY
MEASURING THE RESISTANCE ON THE
2 SIDES VERSUS THE TOP OF THE
FILTER AND WE CAN MEASURE THE
PERMEABILITY BY HAVING THE FORCE
CONJUGATED MOLECULE AND THEN YOU
CAN SEE HOW MUCH OF THAT HAS
BEEN TRANSPORTED SO WHEN WE HAVE
MMP WE CAN SEE THE PERMEABILITY
INCREASES AND THEN THE INHIBITOR
IS RECOVERED AND RESTORED THAT
IS TRUE FOR SEVERAL VARIANTS BUT
THE IMPORTANT THING IS LOOKING
FROM A PERSPECTIVE YOU LOOK AT
THIS LABELED MOLECULES OR
INHIBITORS AND THEN WE ADD THEM
SOME ARE GOING TO STAY THERE
SOME WILL BE TRANSPORTED AND IF
YOU DO HAVE SOMETHING YOU'RE
DELIVERING HERE THEN YOU HAVE A
FOURTH LOCATION THAT NEEDS TO BE
DELIVERED AND TRACKING ALL OF
THAT IS NOT AN EASY TASK AND
REQUIRES US TO HAVE VERY
EFFECTIVE DETECTABLE IMAGING
PROBES TO HAVE AND EXAMPLE HERE
IS THE TIP HOW MUCH IT HAS BEEN
PENETRATED COMPARED TO THE CELL
PENETRATING MOTIF AND THIS IS A
COMBINATION OF BOTH SO THE
PEPTIDE IS VERY GOOD AT
PENETRATING BUT THERE IS A
TREMENDOUS AMOUNT SO HOW MUCH OF
THIS GOING TO EACH OF THESE
STAYS THERE HOW MUCH IS UPTICK
AND THAT BRINGS US TO FIND TUNE
THE TOOLS TO HAVE BETTER
MOLECULAR PROBES BUT ONLY FOR
DIAGNOSTIC BUT POTENTIALLY AND
IS MORE TARGETED DELIVERY
MOLECULES AND THAT BEING SAID IT
BRINGS YOU BACK TO THE BIG
PICTURE OF HOW MULTIFUNCTIONAL
THE ENZYMES ARE SO INTERACTING
WITH A VARIETY OF SOLUBLE AND
THEN TO CONTROL THE CELLULAR
FUNCTION AND FOR US TO ENGINEER
A PROTEIN MODIFIED VERSION NOT
ONLY TO TRACK THEM USING REAL
TIME BUT ALSO TO CONTROL THE
ACTIVITY OF THE INHIBITORS TO
TURN INTO PROTEINS AND THERE ARE
PLENTY OF THEM EXPANDING AS WE
TALK HOWEVER A LOT OF THOSE
TOOLS AND JUST TO BE PREVIOUSLY
ENGINEERED TO BE ABLE TO TURN
OFF AND ON IN A REVERSIBLE
MANNER.
HAS BEEN USED FOR COLOCALIZATION
AND IN OUR CASE IT WAS THE
SYSTEM THAT CAN TURN ON AND OFF
THE EXPRESS AS WELL AS THE
FUSION AND TECHNICALLY TO USE IT
FOR CONTROLLING TRACTION OF THE
INHIBITORS LIKE THE REVERSIBLE
PHOTO CAGING THAT WE HAVE
OPTIMIZE THE SYSTEM WITH THE
USED DISPLAY PLATFORM THAT WE
HAVE AND WE CAN QUANTITATIVELY
MEASURE THE EXPRESSION ON THE
SURFACE AND YOU CAN SEE IN THIS
STATE IT IS PACKED AND CAGED
MOSTLY AND BY EXPOSURE IT IS IN
A STATE SO MORE ROOM TO BINDING
AND ATTRACTION BUT YOU NEED TO
KNOW THAT THIS SPECIFIC
INHIBITOR HAS A VERY IMPORTANT
REGION FOR ATTRACTING AND
INHIBITING TARGET ENZYMES SO TO
TRY TO FIND TUNE AND MODULATE
THIS TRUE MODEL AND THEN TO SEE
HOW IT WORKS WHEN YOU PUT IT AT
THE C TERMINUS AND THEN HAVE THE
REGION THROUGH MORE FREELY
WORKING AND IT BINDS NICELY AND
THEN THE TETRAMER IS FORMED AND
IT HAS A HARD TIME FITTING IN
AND BINDING AND WE SHOWED THAT
IN THE LAB WITH THE SCATTER PLOT
AS YOU CAN SEE WITH THE CONTROL
WE SEE THE NATURAL NON- FUSED
WHICH BINDS THE EXPRESSION WHILE
THE PROTEIN IS EXPRESSED A
LITTLE BIT LESS BUT THEN WE HAVE
IT IN A CAGE MANNER THAT IT IS
EVEN LESS BOUND OR IN THE
DISSOCIATED MANNER AND THEN
BASICALLY IT IS LOST WE HAVE
DONE THE SAME BASIC SYSTEM ON
THE OTHER SIDE OF THE PROTEIN OF
THE TERMINUS THAT YOU CAN SEE
ALREADY THE FUSION EFFECTS TO
SOME LEVEL AND THEN TO PREVENT
TO THE BINDING FROM HAPPENING
AND THE SAME STORY WE HAVE SHOWN
THAT THROUGH THE CYTOMETRY THAT
THIS HAS THE EFFECT THAT WE
EXPECTED LESS AND SAW LESS
BECAUSE THAT IS A TREMENDOUS
THIS TIME BUT WE HAVE SHOWN THIS
ON AND OFF AND HOW IT AFFECTS
THE BINDING TO THE TARGET SO
THEY ARE SIGNALING AT THE SAME
TIME BASICALLY SHOWING THIS TO
HAPPEN SO I WILL GO TO THE
CONCLUSION HOPING THAT I HAVE
CONVINCED YOU THAT THE MODULAR
SCAFFOLDS COMBINED WITH THE
FLUORESCENT CONVERTIBLE SYSTEMS
ARE A GREAT WAY TO NOT ONLY
TRACK OUR INTEREST BUT ALSO THE
FUNCTION AND ALSO LIKE TO THANK
MY RESEARCH GROUP AS WELL AS THE
FUNDING SOURCES AND HELPING US
TO SET UP THE MODELS.
THANK YOU SO MUCH.
>> THANK YOU AND RAPID FIRE
PRESENTERS MAKE YOUR WAY TO THE
FRONT IS PAPER IS OPEN FOR
QUESTIONS.
SO I AND AM CURIOUS WITH THE
PHOTO SWITCHING YOU SHOW THE
DIFFERENT WAVELENGTHS THAT CAUSE
THE CONVERSION CHANGE DO THEY
STAY THAT WAY WHEN ONLY UNDER
THAT LIGHT OR IS IT EACH TIME
THE LIGHT HITS?
>> SINCE IT IS REVERSIBLE IT'S
NOT LOCKED IN THAT SITUATION SO
VERY SOON IT WILL GO BACK TO THE
OTHER BUT NATIVELY IT'S MORE
PRONE TO BE IN THE TETRAMER
STATE.
>> I DON'T SEE ANY ADDITIONAL
QUESTIONS I WILL MOVE ON.
THANK YOU SO MUCH.
[APPLAUSE]
WE ONLY HAVE SO MUCH TIME BUT WE
WANT TO FEATURE AS MANY SPEAKERS
AS WE COULD.
OF THE BREAKOUT SESSIONS AFTER
LUNCH BUT ALSO IF YOU RAPID FIRE
FROM POSTER PRESENTERS TO GIVE
YOU A TEASE OF WHAT THEY ARE
DOING.
THEY ONLY HAVE 5 MINUTES.
SO FOR OTHER PEOPLE DURING THE
RAPID FIRE YOU OF 1 MINUTE TO GO
AND MAKE SURE YOU ARE DONE I
WILL BE MORE AGGRESSIVE.
5 MINUTES EACH AND IN THE ORDER
YOUR LISTED IN THE PROGRAM.
GO.
>> ON BEHALF OF THE CENTER FOR
ONCOLOGY AND OUR ENTIRE RESEARCH
TEAM I WOULD LIKE TO PRESENT OUR
TRANSLATIONAL DEVELOPMENT OF
THERAPEUTICS AND IMAGE GUIDED
TECHNOLOGY FOR TREATMENT OF
CANCER.
MINIMALLY INVASIVE THERAPY IS
REPRESENTS A STRONG COMPONENT
AND THE PARADIGM SHIFT OF
MEDICINE AND ONCOLOGY AND THE
CENTER MISSION IS TO ESTABLISH A
COLLABORATIVE ENVIRONMENT FOR
MULTIDISCIPLINARY TEAMS TO
DEVELOP THESE TECHNOLOGIES
LOCALLY DOMINATE CANCERS FROM
CONCEPT TO PROTOTYPE TO
PRECLINICAL AND CLINICAL THE
SCIENCE DETAILS INCLUDE DESIGN
ENGINEERING AND MODES OF ACTION.
HOW DO WE DO THIS?
DEVELOPMENT OF TECHNOLOGY
THROUGH SAFETY AND EFFECTIVENESS
STUDIES INCLUDING PRE- CLINICAL
PROOF OF CONCEPT AND FEASIBILITY
TRIALS TRANSLATION TO CLINICAL
TRIALS GUIDED BY CLINICAL
EXPERIENCE TO BEDSIDE MODEL.
THE FACILITIES ARE DEDICATED TO
CLINICAL AND CLINICAL RESEARCH
AND RELY ON MULTIDISCIPLINARY
TEAMS SCIENCE AND ENGINEERING
AND IN COLLABORATION ACROSS
MULTIPLE INSTITUTES AND CENTERS
INCLUDING DIAGNOSTIC AND
RADIOLOGY.
THE PRIMARY GOAL OF THE
PRECLINICAL WORK IS TO LAY THE
FOUNDATION FOR TRANSLATION IN
CLINICAL TRIALS TO CLOSE THE GAP
BETWEEN DIAGNOSIS AND THERAPY
THE PRECLINICAL PROGRAM WITH
ANIMAL TRANSLATION IS FAIRLY
BROAD INCLUDING AUGMENTED
REALITY ADMISSION BLOG DASH
AUGMENTATION RULES AND IMAGE
GUIDANCE REGISTRATION AND
SEGMENTATION AND AI.
FOR EXAMPLE MODELING ABLATION
AND MODALITY.
ON THE RIGHT ABLATION SHOWING
EUROS SEGMENTATION AND READ
DISTINCT HE SEPARATED FROM OTHER
STRUCTURES 1 MIGHT BE CONCERNED
ABOUT SUCH AS BLOOD VESSELS.
MODELING DRUG DELIVERY SYSTEMS
PENETRATION UPON HEATING ON THE
LEFT WE CAN SEE ABLATION AND
MODELING DRUG PENETRATION IN
THIS CASE THE PENETRATION INTO
LIVER AND ON THE RIGHT THE DEPTH
OF A BLADDER MODEL COINCIDES
WITH HEAT AND WE CAN ALSO EXTEND
THIS AND THE COMBINATION DRUG
THERAPY COMBINED SYSTEMIC WITH
THE BLADDER WITH HOT WATER
BLADDER IRRIGATION AND THIS IS
TRANSLATING INTO CLINIC.
AND DRUG MODELING ALSO SPATIAL
DRUG PENETRATION AND
DISTRIBUTION MODELING.
YOU CAN SEE WHERE THE DRUG
PENETRATION IS PROLIFERATING.
THEN TRANSLATIONAL INVESTIGATION
IS CONDUCTED IN MODELS OF
DISEASE WE HAVE REPORTED IN THE
TUMOR MODEL AND IN THE CARCINOMA
MODEL MANY STUDIES HAVE
TRANSLATED FROM CONCEPT DIRECTLY
INTO FIRST IN HUMAN WITH MANY
EXAMPLES BUT I WANT TO EMPHASIZE
MULTIDISCIPLINARY TEAM SCIENCE
IS REQUIRED FOR THIS WORK AND I
WILL FOCUS ON A FEW OF THEM THAT
HAVE PIONEERED SOME OF THE
PRACTICE FROM CONCEPT TO ANIMAL
TO PATIENT THE PAINTBRUSH WITH
THERAPEUTICS IN THIS CASE THE
MICROBEADS FOR TREATMENT OF
LIVER TUMORS AND SMALL BEADS
AGAIN FOR TREATMENT OF ACC HE
DEPLOYED LOCAL DRUG THERAPY IS
THE LIPOSOMAL CHEMOTHERAPY WITH
RADIO PRODUCING ABLATION.
FUSION GUIDED INTERVENTIONS
ABLATION MEDICAL GPS THE UPPER
RIGHT GPS ENABLED DEVICES AND ON
THE RIGHT ULTRASOUND FUSION
ENABLED NAVIGATION SYSTEMS AND
MULTI- MODALITY BIOPSY THE
COMBINATION OF PET MRI AND CT
WITH ULTRASOUND FUSION
INTERVENTION AND LASTLY I WOULD
LIKE TO SPEAK TO THE BIOPSY
WONDERFUL EXAMPLE OF
COLLABORATIVE INITIATIVE SCIENCE
PIONEERED THAT HAS PRACTICES AND
A COMBINATION OF MRI PLUS
TRANSRECTAL ULTRASOUND NEW
ENGLAND JOURNAL OF MEDICINE
ARTICLE, FUSION DETECTED
46 PERCENT MORE HIGHLY
AGGRESSIVE PROSTATE CANCER IN
THE STUDY.
THIS IS A WONDERFUL EXAMPLE OF
TRANSLATIONAL SCIENCE FROM
CONCEPT TO BENCH TO PUBLICATION
IN THE COMMUNITY STANDARD OF
CARE PERK I WILL STOP THERE.
THANK YOU FOR YOUR ATTENTION.
[APPLAUSE]
>> ALL THAT WORK IS HAPPENING
HERE AT NIH AND WE WENT TO MAKE
THIS CLEAR WE CAN COLLABORATE
WITH YOU ON THE OUTSIDE WORLDS
OF YOU ARE INTERESTED TALK.
PLEASE.
>> HELLO I'M ASSOCIATE PROFESSOR
OF CHEMICAL AND BIOLOGICAL
ENGINEERING AT THE UNIVERSITY OF
BUFFALO.
FLAGSHIP FOR THE STATE OF NEW
YORK SYSTEM.
MY LAB IS CALLED SYSTEMS
BIOMETRICS WE LOOK AT MODELING
TISSUE REMODELING IN TREATMENTS
ALL CAN BE ORGANIZED BY THINKING
ABOUT THE BALANCE BETWEEN TISSUE
REMODELING AND TISSUE FORMATION
AND DEGRADATION WHERE IT IS
REPLENISHED AND REPLACED BUT IN
SOME DISEASES WE CAN HAVE TOO
MUCH TISSUE DEGRADATION OR TOO
MUCH FORMATION AND WE ARE
INTERESTED IN BALANCING THAT FOR
HOMEOSTASIS AND IN THE DRUG
MOLECULES TO HELP TIP THE
BALANCE FROM THE DISEASE
PHENOTYPE WE ARE INTERESTED IN
NEW TROLL CIRCLES WITH PROBIOTIC
FOOD SOURCES TO PLAY A ROLE THE
CYTOKINES FOR THE IMMUNE SYSTEM
AND OTHER TOXINS SO THAT IS HOW
WE THINK ABOUT PROJECTS IN OUR
LAB AND THIS IS THE CURRENT TEAM
WE HAVE NIH SUPPORT ACROSS
VARIOUS INSTITUTES SO WHEN WE
THINK OF MULTISCALE MODELING WE
ARE PRIMARILY THINKING HOW THE
MOLECULAR NETWORKS INTERACT AND
COMMUNICATE TO THE CELLULAR
NETWORKS AND THEY SECRETE
VARIOUS FACTORS AND MOVE THROUGH
THE TISSUE MICROENVIRONMENTS TO
GIVE RISE TO ORGAN LEVEL
FUNCTION OR DYSFUNCTION AND ALSO
SYSTEMIC TREATMENTS SO WE FOCUS
ON THE CELLULAR NETWORK AND THE
OREGON SCALE BUT DOUBLE IN THE
WHOLE BODY SCALE WE BUILD MODELS
FOR 2 TYPES OF PROBLEMS THE
FIRST IS KINETICS THINKING OF
THE RATES THAT BIOMOLECULES
CELLS OR ORGANISMS CAN REACT OR
INTERACT OR CHANGE STATE FROM
PASSIVE TO ACTIVE DIFFERENT
PHENOTYPES 1 IS A BLOCKER THAT
WE LOOKED AT ACE INHIBITOR
MEDICATIONS CANCER CELL
MIGRATION AND THE WORK ON THE
RIGHT IS FOR BEES AND RESPONSES
TO PESTICIDE HOW WE COULD MODEL
CANCERS AND DO CONSIDER MASS
TRANSPORT.
WITH THE DRUG DELIVERY DEVICES.
AND HOW THAT IS PENETRATING WERE
MIGRATING.
WITH CANCER METASTASIS AND ME
HAVE QUITE A LOT OF WORK RELATED
TO KIDNEY TRANSPORT WITH THE
FILTRATION BARRIERS.
SO WE USE A WIDE RANGE OF
METHODS ALL COMPUTATIONAL THAT
IS A MAJOR WHEELHOUSE.
FOR MOSTLY OUTREACH PURPOSES AND
ELEMENT MODELING AND OPEN SOURCE
TOOLS THAT PEOPLE HAVE DEVELOPED
AND A LOT OF DIFFERENT TOOLS AND
DYNAMIC SYSTEMS I APPRECIATED
THE EARLIER TALK TALK ABOUT
DYNAMIC SYSTEMS ANALYSIS WITH
AGENT -BASED MODELING AS WELL.
THE POSTER IS ORGANIZED BY THE
DIFFERENT METHODS TO TACKLE
DIFFERENT PROBLEMS ACROSS 5
ORGAN SYSTEMS AS THE KIDNEY IS
THE LONGEST STANDING PROJECT IN
THE LAB WE HAVE THINGS LOOKING
AT ORDINARY THE DIFFERENTIAL FOR
CELL SIGNALING KIDNEY CELLS AND
IMMUNE CELLS AND RELATED TO THE
TRANSPORT DIFFERENT LAYERS OF
THE KIDNEY AND WE HAVE THE
SUPPORTED WORK ON I DRUG
DELIVERY AND THE TRANSPORT TO
THE DIFFERENT LAYERS OF
BIOMATERIALS AND THE MOVEMENT OF
THOSE DRUGS AND WORKING ON
CANCER SO METASTASIS AND
MIGRATION AS WELL AS AGENT
-BASED APPROACHES FOR FIBROSIS
ALSO IT CONNECTS THEM TO THAT
TOPIC SO THE POSTER IS REALLY A
MENU OF THINGS IN OUR LAB AS A
SHOWCASE I JUST WANT TO CHAT
PEOPLE ABOUT THE DIFFERENT
PROJECTS HOPEFULLY THAT IS
INTERESTING TO YOU AND ME HAVE
GOOD DISCUSSIONS LATER.
THANK YOU.
[APPLAUSE]
>> WE WILL FIND AN OREGON SYSTEM
YOU'RE NOT MODELING.
[LAUGHTER]
UP NEXT HOUR SPEAKER.
>> HELLO.
AND TODAY I A.M. TALKING ABOUT
THE INVESTIGATION OF THE QUEUE
IN THE COVID 19 USING PULMONARY
ARTERY.
EARLY IN THE COVID 19 PANDEMIC
WAS THE PATIENT'S DYING OF ACUTE
ILLNESS SUBSEQUENTLY THE
INCREASED RESEARCH STROKE THE
CAR DISEASE WAS DOCUMENTED AFTER
RECOVERY FROM EQ COVID 19 TO 1
YEAR AS SEEN IN THE STUDY OF
VETERANS.
SO ENDOTHELIAL DYSFUNCTION IS
FOR MANY CARDIOVASCULAR
COMPLICATIONS AND IT IS
HYPOTHESIZED AS A SUBSET OF THE
DYSFUNCTION.
FIRST WHAT OCCURS AS A RESULT OF
REDUCED METRIC OXIDE IS OTHER
STRESSORS THAT TRIGGERS SOUL
CYCLE ARREST WITH THE PHENOTYPE
AND IT IS NOT DEAD BUT ACTIVELY
RELEASING THE FACTORS AND
SIMILARLY DRUGS HAVE BEEN USED
TO INDUCE THIS SYSTEM IN THE
CELLS AND REDUCES MORTALITY DUE
TO INFECTION.
IN THE PRELIMINARY WORK WE FOUND
IN A DEUCES SO THAT FIRST WE SAW
THAT IF IT IS INTERNALIZED IS
SEEN IN THE IMAGE AS SHOWN IN
RED THE SPIKE PROTEIN WAS
INTERNALIZED BY THE CELLS.
NEXT WE COULD SHOW THAT IT DOES
DEPENDENTLY INDUCE OF PULMONARY
ARTERIAL CELLS AS WELL.
SO NEXT WE SEE HOW WE CAN
COUNTERACT THE EFFECT WE TESTED
AGENTS WHICH IS A
WELL-CHARACTERIZED AGENT TO
PREVENT OR REVERSE THE CELLS AND
THIS HAS BEEN SHOWN TO HAVE
BENEFICIAL EFFECTS OF COVID 19
TRIALS BY THE LAB A COLLABORATOR
IN THE CRITICAL CARE MEDICINE
DEPARTMENT SO WHEN WE FIRST GOT
TO SEE IF THERE WAS ANY EFFECTS
AND THEN WHEN WE COMPARED THE
SPIKE INDUCED CELLS TO THE
CONTROL WE SAW AN INCREASE OF
ACTIVITY WHICH IS USED TO TEST
AND THEN WHEN WE COMPARED IT TO
CELLS INTRODUCED WHEN WE SAW A
DECREASE IN THE CELLS AS WELL SO
THEN WE TESTED THIS AGAINST
RESISTANCE AND WE SAW THAT THERE
WAS A DECREASE OF S-1 WHEN THE
CELLS WERE EXPOSED TO THE S-1
AND PROTEIN AND WE SAW AN
INCREASE SUGGESTING THEY COULD
BE USED TO REDUCE RESISTANCE SO
NEXT WE START TO UNDERSTAND HOW
IT AFFECTS THE OTHER CELL LAYERS
IN THE ARTERY SO WE ARE WORKING
WITH A GROUP AT THE UNIVERSITY
OF UTAH TO CREATE A DEVICE THAT
ACCURATELY MODELS THE ARTERY AND
THEY ARE ABLE TO SHOW 3 DISTINCT
LAYERS SO IN THIS MODEL WE HAVE
THE MODELS IN 3-D CELL CULTURE
APPROXIMATELY BETWEEN 2 AND
10 MILLION CELLS PER MILLILITER
AND THEY CAN SHOW THROUGH
STAINING 3 DISTINCT LAYERS AND
IN OUR LAB WE CAN SHOW THE
INTERFACES BETWEEN THE LAYERS
WHERE THE CELLS ARE INTERACTING.
WE ARE CURRENTLY FABRICATING
THESE TIPS AND IN THE SECOND
IMAGE THERE IS NO CELLS BUT THAT
IS WHERE THEY WILL GO IN THE
RECENT FINDINGS HAVE SHOWN WE
ARE ABLE TO LOAD THE CELLS.
IN SUMMARY SARS-COVID 2 IT IS
INFLAMMATORY WITH CARDIOVASCULAR
CONSEQUENCES SO IT MAY BE
BENEFICIAL OF SEVERE COVID 19 TO
PREVENT LONG-TERM COMPLICATIONS
AND WE HOPE TO LOOK AT CELL TO
CELL INTERACTIONS.
THANK YOU FOR EVERYONE THAT'S
HELP ME ON THE PROJECT AND THANK
YOU FOR LISTENING.
[APPLAUSE]
>> UP NEXT WE HAVE UNIVERSITY OF
NEVADA LAS VEGAS.
>> RIGHT NOW IT IS ABOUT
12:00 O'CLOCK SO I THINK IT IS A
LONG TIME SO QUICKLY I WILL
COMPLETE MY TALK.
PIONEERING THE HUMAN
REPRODUCTION.
SO WHEN WE TALK ABOUT THE
PRODUCTION FOR THE
INTERSTELLAR'S A TRAVEL WE ARE
NOT JUST ADDRESSING THE
TECHNICAL PROBLEM BUT.
>> AND WITH THOSE MARKS THE
ISSUE OF THE HUMAN REPRODUCTION
IN SPACE HAS SHIFTED FROM THE
AREA OF CONCERN FROM ESSENTIAL
PRIORITIES.
SO ON JULY 201969 TO TAKE UP
YONDER SO TODAY OUR CHALLENGE IS
NOT JUST TO ENSURE THAT LIFE
ITSELF CAN SIMPLY REPRODUCE.
SO AS WE PLAN FOR INTERSTELLAR
TRAVEL TO UNDERSTAND IT IS ABOUT
240,000 MILES AWAY.
BUT MARS THE NEXT TARGET IS
ABOUT 140 MILLION MILES FROM THE
EARTH.
THIS DISTANCE IS BIOLOGICAL AND
MEDICAL CHALLENGE BUT THE HUMAN
PROGRAM FOCUSES ON THE MEDICAL
OFFENSE OVER THE LONG-TERM AND
WHAT WAS NEEDED FOR THEM BUT
HOWEVER AND GOING INTO COMBAT
WITH THE HUMAN PRODUCTION SO
HARVARD RESEARCH TO FILL THE
GAPS WITH A NEW METHOD TO ENSURE
THE HUMAN LIFE AND THEN TO
UTILIZE THE ASTRONOMICAL SO WHAT
IS ACOUSTIC LEVITATION AND HOW
IT WORKS AND DIFFERS AND THEN
FOR WHAT IT CAN BE USED FOR AND
THEN IT SHOWS FOR WHAT WE HAVE
DONE.
ACOUSTIC LEVITATION IS A
TECHNIQUE THAT USES SOUND WAVES
AND ASTRONAUT AND PROFESSOR
CONDUCTED THE FIRST CONCEPT
DURING THE IT IS 51 BE SO HOW IT
WORKS.
YOU CAN SEE IT IS
FIRST-GENERATION SO FOR OUR
SOLUTION IN THE SUBJECTS OF MID
AIR.
SO IT CAN BE FOR THE PRIMATE FOR
THE ANTIGRAVITY AND HERE IS OUR
SOLUTION.
WE TRY TO COMBINE BE A CUE STICK
LEVEL -- -- WITH THE ACOUSTIC
LEVEL.
SO FIRST TO SHOW AND THEN WE USE
OUR PROPOSAL PLATFORM TO HIT THE
OBJECTIVE AND ALSO YOU CAN SEE
HERE TO CONTROL THE POSITION.
AND ALSO JUST LIKE THIS WITH THE
FREEBASE.
SORRY ABOUT THAT.
>> THANKS TO OUR SPEAKER.
[APPLAUSE]
INTO THE REMAINING SPEAKER SHOW
YOUR VIDEOS IN YOUR FIRST SLIDES
EVERYBODY IS RUNNING AT A TIME
FOR THE COOL VIDEOS.
>> AND THEN NEXT SPEAKER IS
JEREMIAH.
THANK YOU FOR INVITING ME FOR
THE RAPID TALK TODAY TALKED
ABOUT THE MODEL UNIQUE TUMOR
SUPPLEMENTATION SO BLAST, IS 1
OF THE MOST DETAILED AND HARD TO
TREAT TUMOR TYPES AND THE REASON
WHY IT IS SO HARD TO TREAT IS A
COMPLEX MICROENVIRONMENT IN THE
BRAIN INCLUDING THE BLOOD BRAIN
BARRIER SO THE NEED FOR
DEVELOPING FURTHER TREATMENT IS
TO HAVE A 3-D MODEL TO MIMIC
HUMAN IN VIVO CONDITIONS A
SOLUTION TO THIS PROBLEM IS HERE
IS A DIAGRAM SHOWING THE MODEL
AND AND OUT OF THE PERIPHERY
ALONG WITH THE LABEL AND THE 3
CELL TYPES FORM THE BLOOD BRAIN
BARRIER IN THE BRAIN SO THIS IS
WHAT IT LOOKS LIKE UNDER A
MICROSCOPE AND IT IS SHOWING HOW
IT COULD NICELY FIT FOR HIGH
THROUGHPUT SCREENING.
THE FIRST QUESTION AFTER WE HAVE
THIS MODEL IS TO SEE WHAT
CONSTITUTES GLIOBLASTOMA TUMOR.
WE PERFORM SINGLE CELL AND HERE
NICELY LABELED YOU CAN FIND
THERE ARE 5 DIFFERENT
SUBLIMATION'S AND THEN TO FOCUS
ON THE CENTER 1.
AND THEN TO PERFORM CELL
PSYCHOANALYSIS AND YOU CAN SEE
THIS IS HIDING.
INTERESTINGLY THERE ARE MANY
OTHER SAMPLES WE CAN STILL FIND
THIS SIMILAR POPULATION.
SO THEN WE COMPARE WITH
DIFFERENT SUBPOPULATION FROM
CRITICAL SAMPLES AND ALSO FROM
OUR TISSUE AND THIS IS AMONG THE
TOP OVEREXPRESSED GENES.
WITH A NUCLEOSOME'S TO SEE
DIFFERENT COMPONENTS HERE AND
THE CZAR ALL THE EXAMPLES OF
FACTORS OF THE SUBPOPULATION.
AND WITH THE HISTONE
MODIFICATIONS AND 1 THING IN
COMMON IS THEY ALL INVOLVE
MITOSIS AND PROLIFERATION AND
OVEREXPRESSING CANCER.
AND IT IS A GOOD MARKER FOR THE
POPULATION.
AND THEN TO RESPOND TO DRUG
TREATMENT WHICH IS THE ONLY
APPROVED DRUG.
AND AS YOU CAN SEE HERE YOU WILL
SEE THE BRIGHT MAGENTA THE
DOTS.
AND THEN ACTUALLY IT IS THE
INCREASE OF THE POPULATION.
SO WHAT DOES THIS MEAN?
THE REASON IT IS NOT WORKING
MAYBE WE CAN MANIPULATE THAT.
AND AS A SUMMARY AND THEN ALSO
TO FIND THE MAN CLINICAL
EXAMPLES AND IT INCREASES UNDER
TREATMENT AS WE ARE
INVESTIGATING TO INCREASE THE
KILLING SO THANK YOU TO MY GREAT
COLLABORATORS.
THANK YOU.
>> AND OUR FINAL SPEAKER?
>> I AND VERY EXCITED TO BE HERE
TO TALK ABOUT THE RESEARCH WORK
WE ARE DOING REGARDING THE
FUNCTIONAL LIFE INJECTABLE
INFORMATION SUPPORTED BY THE
MATRIX.
SO THE IDEA WE ARE HAVING IS
THAT LOOK AT THAT TRADITIONALLY
THE CONTROL IS CRUCIAL IN THE
CASE THAT IF GEL FORMS TO
RAPIDLY BECOMES ON INJECTABLE IF
IT COMES TO SO YOU ARE NOT BE
ABLE TO RETAIN ANY COMPONENTS
WHETHER OR THERAPEUTICS OR GEL
COMPONENTS.
SO WHAT WE HAVE PROPOSED HERE IS
TO HAVE AN ELASTIC MATRIX OF
SEQUESTERING SOLUTIONS.
AND THEN ALLOW THAT TO FORM.
SO FIRST I WOULD LIKE TO
INTRODUCE YOU ON THE FORMATION
OF THE MATRIX IT IS BY USING
MATERIAL AND THEN COUPLED WITH
IN THE CASE THE ICE CRYSTALS
MELT AWAY AT THE END IT
GENERATED THOSE STRUCTURES THAT
ARE CAPABLE OF SEQUESTERING AS
YOU CAN SEE SO THAT INJECTABLE
THAT WE ARE USING THAT WE HAVE
THE COMPONENTS AND LOADED INTO
THE MATRIX AND THEN WE SUPPORTED
THE FORMATION.
MORE IMPORTANTLY TO SEQUESTER OR
THE RETENTION OF THE
THERAPEUTICS IS AN IMPORTANT
TOPIC IN DRUG DELIVERY AND IT IS
BY IN COOPERATION THROUGH THE
CHEMISTRY AND WE CONJUGATED
CAPABLE OF BINDING TO THE
THERAPEUTICS AND OUR RESULTS
HAVE SHOWN THAT THIS ELASTIC
MATRIX HAS ALLOWED THE HYDROGEL
TO FORM AND IT IS CAPABLE OF THE
FIRST RELEASE OF THERAPEUTICS
WHICH IN THIS CASE WE ARE
STUDYING THE RELEASE AND WE
FURTHER WANTED TO SEE THE
CAPABILITY OF THIS MATRIX IN
TERMS OF SUPPORTING CELL
ATTACHMENT AND ARE RESULT HAS
SHOWN IN COOPERATION OF HYDROGEL
CAPABLE OF SEQUESTERING TO ALLOW
THE CELLS TO BE ATTACHED IN THE
SYSTEM AND MORE IMPORTANTLY IT
IS THE BIOTHERAPEUTICS ARE
RELEASED SLOWLY AND A SUSTAINED
FASHION AND CAPABLE OF RETAINING
BIOACTIVITY AND THE ANSWER IS
YES YOU CAN SEE THAT THE
THERAPEUTICS THAT ARE RELEASED
ARE CAPABLE OF INDUCING THE
MIGRATION OF SMOOTH MUSCLE CELL
AND THEN TO SEE THE COMBINATION
INSIDE THE COMPOSITE AS WELL AS
TO BE SEQUESTERED INSIDE THE
HYDROGEL MATRIX.
AND THEN AND SUPPORT
PROLIFERATION OF MUSCLE CELLS
AND THE RESULT IS ONCE
AGAIN, YES USING THE VIABILITY M
THE DYE WE CAN SEE THEY ARE
CAPABLE OF BEING RETAINED INSIDE
THE HYDROGEL MATRIX AS WELL AS
CONTINUING TO PROLIFERATE.
WITH THAT BEING SAID, I HAVE
SHOWN IN THIS TALK THE STRUCTURE
ALLOWS THE ADEQUATE INFILTRATION
FOR THE AFFINITY BASED
INJECTABLE HYDROGEL AND WE THINK
THIS MATRIX AND IN COOPERATION
CAN EFFECTIVELY SEQUESTER GROWTH
FACTORS FOR SUSTAINED-RELEASE
AND PRESERVE THE BIOACTIVITY OF
THE THERAPEUTICS.
WITH THAT BEING SAID I WOULD
LIKE TO THINK THE RESEARCH WAS
SUPPORTED BY THE NIH WHICH IS AN
HONOR TO BE HERE TO SHARE WITH
YOU THE RESEARCH WE ARE DOING
AND THANK YOU PENN STATE TO THE
WHERE I AM DOING MY RESEARCH
THANK YOU.
[APPLAUSE]
>> THANK YOU TO ALL OF OUR
RAPIDFIRE SPEAKERS.
PLEASE COME BACK IN THE
AFTERNOON.
WE WILL SEE THEMATICALLY IT
TAKES A TURN FOR THE AFTERNOON
SESSION.
YOU ARE FREE FOR LUNCH THERE ARE
SEVERAL DIFFERENT LOCATIONS THAT
YOU CAN GRAB FOOD WE ALSO HAVE
THE POSTERS AVAILABLE RIGHT NOW
HOPING PRESENTERS WILL BE
PRESENT AND THEN TAKING THE LAST
HALF HOUR TO EAT.
IF EVERYBODY GOES THE CAFETERIA
AT THE SAME TIME THEN NOBODY
EATS.
WE WILL CHANGE THE POST -- -- IS
A POSTERS UP 130.
THANK YOU VERY MUCH YOU CAN SEE
HOW THE AFTERNOON BREAKS APART.
WE WILL SEE WHAT THE BREAKOUT
SESSION.
>> OKAY, GOOD AFTERNOON,
EVERYONE!
AND THANKS TO THOSE WHO'VE COME
BACK AN JOINED US IN THE ROOM
PLUS THOSE JOINING ON THE NIH
VIDEOCAST.
THIS IS THE BREAKOUT SESSION
THAT WE'VE BEEN HAVING, THERE
ARE SOME INDEPENDENT RESEARCH
TALKS HAPPENING IN SIX DIFFERENT
AREA, BUT THIS IS THE CENTRAL
PANEL WHERE WE WANTED TO TALK
ABOUT THIS TRANSLATION OF WORK
AND THINK ABOUT THINGS FROM THE
INDUSTRY SIDE, INNOVATION, AND
THEN WHAT NIH OR GOVERNMENT
PLAYS A PART AS WELL BECAUSE
THERE'S SOMEONE HERE WHO ALSO
HAS A LOT OF INTERACTION WITH
DOD.
I'M MANU PLATT, JUST THE
MODERATOR FOR THIS AND HOPEFULLY
WON'T HAVE TO SAY MUCH BECAUSE
WE HAVE SOME EXCITING SPEAKERS
AND THEY ENJOY SPEAKING SO THAT
WILL BE GREAT FOR US.
>> YOU'RE NOT JUST THE
MODERATOR, COME ON.
>> THAT'S NICE.
BUT I WANTED TO READ SOME BRIEF
INTRODUCTIONS SO YOU CAN KNOW
MORE ABOUT WHO THEY ARE.
SO I GUESS I'LL START WITH THE
END, OUR KEYNOTE SPEAKER FOR
THIS AFTERNOON IS ALSO THE DEAN
OF THE GRANGER COLLEGE OF
ENGINEERING AND PROFESSOR OF
BIOENGINEERING AT THE UNIVERSITY
OF ILLINOIS URBANA-CHAMPAIGN.
FROM 2014 TO 2017, HE WAS A
MEMBER OF THE CORE FOUNDING TEAM
AND CO-CHAIR OF THE INAUGURAL
CURRICULUM COMMITTEE FOR THE
UIUC COLLEGE OF MEDICINE.
THE WORLD'S FIRST ENGINEERING
BASED COLLEGE OF MEDICINE.
HE HAS OVER 300 PUBLICATIONS, 60
PATENTS AND IS A MEMBER OF THE
NATIONAL ACADEMY OF MEDICINE AND
THE AMERICAN ACADEMY OF ARTS AND
SCIENCES.
HIS RESEARCH GROUP IS INTERESTED
IN DEVELOPING NEW TECHNOLOGIES
FOR PERSONALIZED AND PRECISION
MEDICINE AND IN 3D
BIOFABRICATION OF CELLULAR
SYSTEMS.
HE'S ALSO SPUN OFF MULTIPLE
COMPANIES AND IS THE CO-FOUNDER
OF PRONOSIS INC., DEVELOPING
POINT OF CARE CENTERS FOR
ANALYTICS FOR SEPSIS
STRATIFICATION, RAPID DETECTION
OF PATHOGENS USING CRISPR
TECHNOLOGY AND OTHERS.
SO THANK YOU.
SITTING TO THE LEFT OF
DR. BESHEAR IS MY OLD FRIEND DRL
DIRECTOR OF THE THERAPEUTICS
DEVELOPMENT UNIT AT BIOGEN WHICH
IS IN CAMBRIDGE, MASSACHUSETTS.
LEADING CLINICAL TRIAL
ACTIVITIES FOR TREATMENT OF
NEURODEVELOPMENTAL DISORDERS.
SHE STUDIED NEUROENDOCRINE
REGULATION OF IMMUNITY AS A
POSTDOCTORAL FELLOW AT THE
ILLUSTRIOUS NATIONAL INSTITUTES
OF HEALTH AND CONTINUED THIS AT
THE U.S. FOOD AND DRUG
ADMINISTRATION TAKING ON
ADDITIONAL RESPONSIBILITIES.
DR. BUTTS HAS HEL A NU HELD A NF
ROLES INCLUDING NOW APPROVED IN
U.S. AND EU FOR MULTIPLE
SCLEROSIS, SHE SERVED ON THE
INAUGURAL COHORT OF BIOGEN'S
PORTFOLIO TRANSFORMATION TEAM
LEADING THE PROBABILITY OF
SUCCESS AND INITIATIVES ON
CHANGE MANAGEMENT, AND PROJECT
TEAM LEARNING AND HEALTH.
TO THAT LEFT, NOW COMING TOWARDS
ME, IS DR. VINCENT HO, WHO I
FIRST MET ON NIDID COUNCIL.
VINCENT HO IS CHAIR AND
PROFESSOR OF THE DEPARTMENT OF
RADIOLOGY AND BIOENGINEERING AND
DIRECTOR OF THE 4D BIO3 CENTER
FOR BIOTECHNOLOGY AT THE
UNIFORMED SERVICES UNIVERSITY.
AND DIRECTOR OF RESEARCH FOR THE
DEPARTMENT OF RADIOLOGY AT
WALTER REED NATIONAL MEDICAL
CENTER.
DR. HO HAS SPENT THR THREE DECAS
SERVING MILITARY BENEFICIARIES.
DEMONSTRATING HIS LONG HISTORY
OF TECHNOLOGY INNOVATION.
HIS CURRENT RESEARCH FOCUSES ON
THE DEVELOPMENT OF NOVEL MRI
TECHNOLOGY, AUSTERE NEED OF
BIOTECHNOLOGY, ASK HIM WHAT THAT
MEANS, IT'S REALLY INTERESTING,
TISSUE ENGINEERING AND HUMAN
PERFORMANCE.
ALL FOR THE BENEFIT OF SERVICE
MEMBER REDENESS AND HEALTH.
4D BIOCUBED ASPIRES TO BE A K DD
FEDERAL RESOURCE BUT ALSO WHICH
IS WHY YOU'RE HERE WITH
NON-FEDERAL ACADEMIC
INSTITUTIONS AND INDUSTRY
PARTNERS.
NEXT UP, DR. BRADFORD WOOD IS
ACTING MEDICAL DIRECTOR FOR THE
BIOMEDICAL TECHNOLOGY DATA
CENTER, WEE GLAD TO HAVE YOU.
DR. WOOD IS THE FOUNDING
DIRECTOR OF THE NIH CENTER FOR
INTERVENTIONAL ONCOLOGY WHICH
TRANSLATES TECHNOLOGIES AND
PARADIGMS FOR FIRST IN HUMAN
TREATMENTS FOR CANCER AND
CULTIVATES INTERVENTIONAL
RADIOLOGY FRAMEWORKS --
RADIOLOGY APPLICATIONS WITHIN A
MULTIDISCIPLINARY FRAMEWORK TO
APPLY BIOMEDICAL ENGINEERING TO
MEET REAL LIFE UNMET CLINICAL
NEEDS.
HIS TEAM'S ACHIEVEMENTS INCLUDE
HELPING TO PIONEER SEVERAL
TECHNOLOGIES FROM CONCEPT TO
BENCH TO PATIENT, AND HIS TEAM
WAS FIRST IN HUMAN FOR A NUMBER
OF DEVICE DRUG COMBINATIONS
INCLUDING PROSTATE CANCER, MRI,
AND BIOPSY AND ABLATION.
WE HEARD A LITTLE ABOUT THAT
THIS MORNING, IMAGEABLE DRUG
ELUDING BEADS FOR CHEMO
UTILIZATION OF LIVER TUMORS AND
NAVIGATION SOFT WAR FOR IR BUT
ALL RELIED ON TEAM SCIENCE, HE
DEFINITELY BELIEVES IN TEAM
SCIENCE.
GLAD TO HAVE YOU.
FINALLY FRESH OUT OF THE OR,
MAYBE HE HAS TO GO BACK IF HE
GETS A TEXT OR PAGE, IS
DR. PETER PINTO.
HE'S A SENIOR INVESTIGATOR AND
FACULTY MEMBER IN THE UROLOGIC
ONCOLOGY BRANCH AND DIRECTOR OF
THE UROLOGIC ONCOLOGY FELLOWSHIP
PROGRAM HERE AT THE NCI.
HE IS NATIONALLY AND
INTERNATIONALLY RECOGNIZED AS AN
EXPERT IN THE MINIMALLY INVASIVE
TREATMENT OF UROLOGICAL CANCERS,
SPECIALIZING IN LAPAROSCOPIC AND
ROBOTIC SURGERY FOR PROSTATE,
KIDNEY, BL BLADDER AND TESTICULR
CANCERS.
HIS RESEARCH EFFORTS ARE
CENTERED ON INVESTIGATION OF
MULTI-PARAMETRIC MRI AND
PROSTATE CANCER TO IMPROVE
DIAGNOSIS WITH MP MRI, AND
CREATION OF A TUMOR DIRECTED
BIOPSY DEVICE.
NICE.
DEVELOP MANAGEMENT OF IMAGE
GUIDED PROSTATE CANCER THERAPY
AND OTHER PHARMACOTHERAPIES IN
THE MANAGEMENT OF LOCALIZED OR
LOCALLY ADVANCED PROSTATE
CANCER.
ALSO FOR IMPROVING SURGICAL
PLANNING OUTCOMES.
I'M NOT GOING TO TALK FOR THE
REST OF THIS SESSION BECAUSE
THAT WAS A LOT OF TALKING BUT I
DO WANT TO OPEN IT UP TO THE
FIRST QUESTION WHICH I DID SEND
TO YOU ALL IN ADVANCE AND IF YOU
WERE GOOD STUDENTS YOU WOULD
REMEMBER THIS, BUT I WOULD ASK
IF EACH PANELIST COULD JUST
SPEND A FEW MINUTES ADDING
WHATEVER DETAIL YOU NEED TO TO
YOUR PROFILE BUT TELL -- NEW
TECHNOLOGIES AND ANY GUIDANCE TO
OTHERS INTERESTED IN PURSUING
PATHS ALONG THE WAY.
>> SO THANK YOU, IT'S AN HONOR
TO BE HERE AND TO BE NEXT TO MY
WORK WIFE FOR 20 YEARS.
[LAUGHTER]
DR. BRAD WOOD.
I WILL END IT WITH THAT.
LISTEN, AS SURGEONS, YOU'RE A
UROLOGIC SURGEON, IT'S OFTEN
THAT WE DON'T KNOW WHAT WE NEED.
IT SOUNDS ODD.
TO SAY WE DON'T KNOW WHAT WE
NEED.
BUT WE NEED KIND OF DISRUPTIVE
INNOVATION TO REALLY ADVANCE THE
OPPORTUNITY TO -- IN THIS CASE
FOR CANCER, CURE A PERSON OF
THEIR CANCER.
SO IN THAT REGARD, WHAT I'VE
LEARNED IS TO KEEP MY MIND OPEN
AND MY EARS OPEN AND TO PARTNER
WITH INDUSTRY AND WITH
SCIENTISTS THAT HAVE IDEAS THAT
WHEN I THINK THEY'RE CRAZY, I
HOLD ON TO THEM.
FOR DEAR LIFE.
BECAUSE THOSE ARE THE IMPORTANT
ONES.
AND YOU HEARD A LITTLE BIT ABOUT
WHAT DR. WOOD AND MYSELF AND
MANY OTHERS AT THIS INSTITUTION
WORKING WITH INDUSTRY COULD
CREATE -- WE'VE CREATED A NEW
WAY OF FINDING PROSTATE CANCER.
AGAIN, SOMETIMES I FORGET ABOUT
THIS, BUT UNTIL THE WORK HERE,
YOU KNOW, PROSTATE CANCER WAS
ALSO FOUND A BIT TOO LATE IN
ADVANCED STAGES, WE FOUND IT IN
A BETTER WAY WITH IMAGING AND
BETTER DEVICES.
IF YOU ASKED THE YOUNGER VERSION
OF ME WHEN I WAS IN TRAINING IN
BALTIMORE AT JOHNS HOPKINS, DO I
NEED THAT, I WOULD SAY NO, WE'RE
DOING FINE AS WE ARE.
MY ONLY ADVICE WOULD BE WHEN YOU
THINK IT'S A LITTLE CRAZY, A
LITTLE BIT OUT OF THE
ORDINARILY, PLEASE HOLD ON TO
THAT, WORK THROUGH IT.
BECAUSE THOSE ARE THE MEDICALLY
CHANGING DEVICES THAT WE HOLD
TRUE TODAY.
THANK YOU.
>> AND SINCE WE DO EVERYTHING
TOGETHER, I'LL CHIME IN AND ADD
THAT NONE OF THE REAL
DEVELOPMENTS THAT ARE IMPACTFUL
HAPPEN IN A VOID AND YOU CAN'T
DO THEM WITHOUT STEPPING OUTSIDE
OF YOUR TUNNEL VISION
SPECIALTIES AND PATHWAYS, EVEN
BME, WHATEVER YOUR SPECIALTY IS,
YOU GO TO THE SAME MEETINGS,
READ THE SAME JOURNALS, IT'S
ALMOST INSES TAU US THE WAY YOU
REGURGITATE THE SAME IDEAS.
THAT'S WHAT'S BEAUTIFUL WORKING
EVERY DAY WITH SOMEBODY THAT'S
CRAZY NEXT TO ME IN A DIFFERENT
SPECIALTY.
NOWHERE ELSE OTHER THAN NIH IS
THERE THE OPPORTUNITY TO HAVE
THIS TRANSLATIONAL GOALS AND
HAVE MOLECULAR IMAGING,
ENGINEERS COUNTLESS ENGINEERS
AND SOFTWARE ENGINEERS, ONE OF
THEM SITTING IN THE AUDIENCE,
KEVIN MA CLEAR EE, AND DIFFERENT
SPECIALTIES SIDE BY SIDE,
SHOULDER TO SHOULDER, IN THE
CLINIC CLINCLINICAL SUITE, COMIH
SOLUTIONS, IT'S ITERATIVE TRYING
TO REFINE THAT PROCESS BACK AND
FORTH, TO THE BENCH, TO THE
SOFTWARE, TO THE ANIMAL LAB, TO
WHEREVER YOU NEED TO GO TO
ITERATE THAT SOLUTION.
AND THAT REQUIRES TAKING OFF
YOUR HE GO EGOS, BUT THE PATENT
PROBLEM ALSO COMES TO BE A
HURDLE.
SO IT'S HOW YOU THINK ABOUT
PATENTS, HOW YOU THINK ABOUT IP.
I CAN'T TELL YOU THE NUMBER OF
GREAT IDEAS THAT WERE SQUASHED
BECAUSE OF THE PURSUIT OF
OWNERSHIP, OF PATENTS OR THIS
VISION OF PATENTS MEANS I'M
GOING TO BE FAMOUS OR MAKE MONEY
OR WHATEVER IT IS, AND YOU'VE
GOT TO GIVE UP THAT OWNERSHIP
BECAUSE NOBODY WHO TAKES CREDIT
FOR ANYTHING ACTUALLY DID IT
ALONE.
HE SAYS TO ME ALL THE TIME, HE
SAYS YOU INVENTED THIS, YOU
INVENTED THAT.
NOBODY DOES ANYTHING ALONE.
AND WE HAVE TO TAKE CREDIT FOR
IT IN ACADEMICS BECAUSE WE LEARN
TO SELF-PROMOTE AND SOMETIMES
ALL TOO OFTEN AND TOO WELL.
REALLY EVERY GOOD TALK SHOULD
START WITH A PICTURE OF YOUR
TEAM, AND IT'S -- THIS IS
DEFINITELY TRUE IN THE SETTING
WHERE YOU'RE TRYING TO SIT SIDE
BY SIDE AND GET BIOMEDICAL
ENGINEERING TOOLS INTO THE
CLINIC TO MEET THAT UNMET NEED.
FOLKS WILL DEFINE THAT SOLUTION
LOTS OF TIMES IN A VOID, COME
BACK WITH A TOOL, A YEAR LATER,
SIX MONTHS LATER, A MONTH LATER.
THAT DOESN'T WORK.
BAKED INTO THE WALLS OF THIS
CLINICAL RESEARCH CENTER IS LABS
RIGHT NEXT TO THE PATIENT
FLOORS.
THAT REQUIRES THIS FERTILE
INTERACTION AND THE ATMOSPHERE
AND OPPORTUNITIES WHICH ARE
REALLY UNIQUE HERE.
>> WE HAVE TO THANK THE
PATIENTS.
>> THERE YOU GO.
>> WE HAVE TO THANK THE
PATIENTS, WHO REALLY BITE INTO
THIS, RIGHT?
GOT TO THANK THE PATIENTS TOO,
THANK YOU.
>> VINCENT?
>> I SHARE THE THOUGHTS OF PINTO
AND BRAD, REALLY, MEDICINE BY
NATURE IS MULTIDISCIPLINARY, AND
AS A RADIOLOGIST, WE'RE ALWAYS
PROBLEM SOLVING, TRYING TO
FIGURE OUT THE DIFFERENTIAL
DIAGNOSIS, AND WORK WITH THE
CLINICAL COLLEAGUES AS FAR AS
THE INTERVENTION OR THE
THERAPEUTIC OPTIONS THAT WE
HAVE.
AND I'VE SPENT ALL MY CAREER
PREDOMINANTLY WITHIN THE
DEPARTMENT OF DEFENSE AND IN
MILITARY MEDICINE, AND IN
PARTICULAR, I THINK MILITARY
MEDICINE FORCES US, ACTUALLY
CHALLENGES US TO BE INNOVATIVE,
BECAUSE A LOT OF TIMES WE DON'T
NECESSARILY HAVE EVERYTHING WE
WOULD HAVE, ESPECIALLY WHEN
YOU'RE OVERSEAS, IT'S NOT LIKE
YOU CAN GO AND ORDER SOMETHING
AND GET IT IN THE AFTERNOON.
AND IN AN OPERATIONAL SETTING
WHEN WE'RE DEPLOYED IN AUSTERE
ENVIRONMENTS, A LOT OF OTHER
ISSUES COME TO BEAR.
JUST HAVING CLEAN WATER.
>> DESCRIBE WHAT AN AUSTERE
ENVIRONMENT IS FOR PEOPLE WHO
AREN'T USED TO THAT TERM.
>> NORTH CAROLINA.
RIGHT?
SO LIKE RIGHT AFTER THE
HURRICANE, YOU DON'T HAVE POWER,
YOU DON'T HAVE WATER, YOU DON'T
HAVE ENERGY, ELECTRICITY.
RHODES ARE OUT.
YOU'RE IN THE MIDDLE OF NOWHERE.
AND THAT'S IT.
WHATEVER YOU BROUGHT IS WHAT YOU
HAVE.
AND SO YOU'VE GOT TO THINK ABOUT
OUR MEDICS, OUR PHYSICIANS'
ASSISTANTS.
HOW MUCH CAN YOU CARRY, WHAT DO
YOU TAKE?
YOU CAN'T TAKE EVERYTHING.
SO YOU HAVE TO BE EFFICIENT.
WHAT KIND OF POWER SOURCES DO
YOU HAVE?
AND SO AUSTERE ENVIRONMENTS IN
OPERATIONAL MEDICINE PRESENTS A
CHALLENGE AS DISASTER MEDICINE,
DISASTER PREPAREDNESS.
SO WE HAVE TO IMPROVISE AND
FIGURE OUT WHAT THE BEST
SOLUTIONS ARE.
>> GREAT, THANK YOU.
CHERIE.
>> SO NUMBER ONE, I WANT TO
THANK YOU FOR BRINGING ME BACK
HOME, AND I LOVE THAT ALL OF US
ARE COMING FROM GOVERNMENT
BECAUSE THIS IS VERY RARE.
SO I WANT TO TALK A LITTLE BIT
ABOUT -- I AGREE WITH EVERYTHING
YOU ALL HAVE SAID AND I WANT TO
TALK A LITTLE BIT ABOUT MY
EXPERIENCE IN INDUSTRY.
YOU WORK FOR WHAT WAS -- YOU
KNOW, WHAT'S KNOWN AS A DRUG
COMPANY, BUT FROM MY DAYS AT
FDA, WHAT PEOPLE USUALLY FORGET
AS THEY'RE DEVELOPING DRUGS IS
THE MANUFACTURING PIECE.
LIKE THAT'S WHERE A LOT OF DRUGS
ACTUALLY FAIL.
THEY'RE NOT FAILING BECAUSE THE
DRUG ISN'T GOOD, THE STUDY
WASN'T DESIGNED RIGHT, BUT
BECAUSE THEY CAN'T MANUFACTURE
PROPERLY.
BUT I WILL TELL YOU THE STORY
FROM MY DAYS WHEN WE WERE
DEVELOPING PLAGRITY, WE WERE
TRYING TO GO FAST, WITHOUT
LOSING QUALITY, AND SO AS WE
WERE LOOKING TO GET IT APPROVED,
WE SAID OKAY, WE REALLY WANTED
TO BE AN AUTO INJECTOR BECAUSE
WE KNOW THAT'S WHAT PATIENTS
WANT BUT IT LITERALLY TAKES TWO,
THREE YEARS TO DEVELOP AN AUTO
INJECTOR.
SO WE SAID OKAY, WE'RE GOING TO
GO WITH THE PREFILLED SYRINGE TO
GET IT OVER THE FINISH LINE, BUT
WE ALSO HAVE TO BE THINKING
ABOUT THE TIMELINE IT TAKES TO
DO THE AUTO INJECTOR.
AND SO THAT'S WHAT MOST PEOPLE
FORGET, IS IF YOU'RE THINKING
ABOUT THE DELIVERY SYSTEM, YOU
CAN'T THINK ABOUT THE DELIVERY
SYSTEM BY THE TIME YOU GET TO
PHASE 3 AND THEN WE'LL JUST
PIVOT.
YOU ACTUALLY HAVE TO BE THINKING
ABOUT IT AT THE SAME TIME AS
WHEN YOU'RE GOING INTO THE
CLINIC.
THIS IS SOMETHING PEOPLE REALLY
DON'T APPRECIATE ABOUT THE
ENTIRE DRUG DEVELOPMENT PROCESS,
THEY'RE KIND OF THINKING ABOUT
DEVICES, BUT THERE'S A DEVICE
BECAUSE THERE'S A DELIVERY
SYSTEM FOR THAT DRUG, SO THINK
ABOUT IT THAT WAY.
DIAGNOSTICS ARE THE SAME WAY.
>> AND IF YOU HAVE ANY QUESTIONS
IN THE AUDIENCE, PLEASE APPROACH
THE MICROPHONES AND AFTER WE GET
THIS, WE'LL TAKE SOME QUESTIONS.
>> THANK YOU, MANU, FOR HAVING
THIS FORUM.
SO I ACTUALLY WORKED IN INDUSTRY
FOR THE FIRST SIX YEARS OF MY
CAREER, I WORKED AT NATIONAL
SEMICONDUCTOR, WHICH IS A CHIP
COMPANY.
AND MY PH.D. WAS ALL IN
ELECTRONICS.
BUT I GOT REALLY INSPIRED WITH
BIOLOGY IN THE LAST SEMESTER OF
MY PH.D.
AND SINCE THEN, I WORKED SIX,
SEVEN YEARS TO KIND OF MAKE THE
SWITCH, BUT IN INDUSTRY, WE KIND
OF WENT THROUGH THAT WHOLE
PROCESS OF R & D BUT REALLY
SMALL R, BIG D, THEN TRANSLATED
IT THROUGH TO MANUFACTURING, SO
WE ACTUALLY DEVELOPED LIKE SIX
TECHNOLOGIES THAT WERE
COMMERCIALIZED IN THE
SEMICONDUCTOR FABS, BUT I WAS
ALWAYS VERY INTERESTED IN
COMBINING THAT WITH BIOLOGY.
SO I COULD ONLY DO THAT IN
ACADEMIA, SO I DECIDED TO COME
BACK TO ACADEMIA.
AND ACTUALLY I REMEMBER THE VP
OF MY DIVISION SAID THAT, YOU
KNOW, I CAN PAY YOU LESS AND YOU
CAN WORK HARDER RIGHT HERE, YOU
DON'T HAVE TO GO TO ACADEMIA.
BUT NEW YEAR'S ANYWAY I'M GLAD E
THE SWITCH.
WE WERE INTERESTED IN BASIC
RESEARCH BUT ALSO USE INSPIRED
RESEARCH AND I'VE BEEN FORTUNATE
TO HAVE COFOUNDED SOME COMPANIES
WITH MY STUDENTS EVERY SINGLE
ONE OF THEM WAS WITH ONE OF MY
STUDENTS TO OUR ACTIVE -- TWO
ARE ACTIVE NOW THAT I'LL SHARE
LATER BUT I THINK ONE THING THAT
I LEARNED IS THAT WHAT'S MOST
IMPORTANT ACTUALLY IN MY OPINION
IN THESE STARTUPS OR TRANSLATING
TECHNOLOGY ESPECIALLY FROM THE
UNIVERSITY, AT A UNIVERSITY
WE'RE PRODUCING TALENT, WE'RE
PUBLISHING PAPERS AND I THINK
PART OF WHAT REALLY THE END GOAL
IS, PRODUCE TALENT FOR THE
WORLD, ADVANCE THE STATE OF
KNOWLEDGE AND UNDERSTANDING,
AND, OF COURSE, I THINK MORE AND
MORE, AND DEPENDING ON PERSONAL
INTEREST, YOU ALSO WANT TO
TRANSLATE THOSE TECHNOLOGIES AND
THAT HE WHAT THE WHOLE
EQUISYSTEM IS NEEDED DO THAT.
BUT AT THE END OF THE DAY, IN
ALL CASES, THE INITIAL IDEA THAT
WE STARTED WITH TO WHAT WAS
GOING TO BE THEN A PRODUCT WAS
LIKE DRAMATICALLY DIFFERENT.
WAS DRAMATICALLY DIFFERENT.
AND THE COMPANY TOOK THAT
INITIAL IDEA AND THEN THE RIGHT
ONES THAT MOVED FORWARD WERE THE
ONES THAT WERE ABLE TO ADAPT, BE
NIMBLE, CHANGE, AND STAY FOCUSED
ON THE CUSTOMER AND THE PRODUCT.
NOT NECESSARILY EVEN THE
ORIGINAL TECHNOLOGY IN ITS
ORIGINAL FORM.
SO I THINK WHAT'S MOST IMPORTANT
IS TALENT AND PEOPLE LIKE WHO
ARE THE PEOPLE DRIVING IN THE
STARTUPS AND THERE'S A LOT OF
LUCK INVOLVED, ORVETION BUT JUST
JUST THAT PERSEVERANCE AND
REALLY KEEPING AT IT WITH
WANTING TO MEET A CLINICAL NEED,
IN THIS CASE IN THE BIOMEDICAL
SPACE, HAVING THAT CLINICAL NEED
AND REALLY, REALLY, REALLY GOOD
UNDERSTANDING OF THE CLINICAL
NEED AND WHAT IS -- HOW WILL IT
BE USED BY PHYSICIANS WHO ARE
DOING VERY IMPORTANT JOBS WITH A
LOT OF PRESSURE, WITH A LOT OF
SORT OF TIME DEMANDS -- I MEAN
DEMANDS ON THEIR TIME AND
SOMETIMES VERY LITTLE INFORMING,
BUT THEY HAVE TO MAKE THE
DECISION AND MOVE FORWARD, SO
HOW DO WE HELP THAT, HOW DO WE
PROVIDE MORE INFORMATION, HOW DO
WE PROVIDE TOOLS TO MEET, TRULY,
A CLINICAL NEED, WHETHER IT'S
THE PHYSICIAN, WHETHER IT'S THE
INDIVIDUAL, WHETHER IT IS SOME
PHARMACEUTICAL OR BIOMEDICAL
INDUSTRY.
SO I THINK THAT END USE AND THE
FACT THAT WHEN YOU START A
COMPANY FOR THOSE OF WHO YOU
MIGHT BE THINKING, YOU HAVE TO
BE REALLY COMMITTED TO THE GOAL
OF TRANSLATING A TECHNOLOGY AND
MAKING AN IMPACT BUT YOU CAN'T
BE -- IT WILL CHANGE, IT WILL
CHANGE ALONG THE WAY, IN ALL
CASES THINGS WERE DRAMATICALLY
DIFFERENT FROM WHERE WE STARTED.
SO I'LL STOP THERE.
>> THANK YOU FOR THAT.
AGAIN, OPEN FOR QUESTIONS.
LOOKS LIKE WE HAVE ONE OVER
HERE.
>> THIS IS MY SOFTBALL QUESTION.
TO ANYONE UP THERE.
SO I'M LOOKING AT THE TITLE,
IT'S INDUSTRY, INNOVATION, NIH.
AND I'LL JUST CALL THAT
GOVERNMENT, PATIENT CARE,
INDUSTRY FROM STARTUP ALL THE
WAY TO ESTABLISHED LARGE
COMPANIES THAT ARE ON FORTUNE
500.
BUT BETWEEN IT, YOU HAVE THE
WORD INNOVATION.
SO KNOWING BRAD VERY WELL AND
PETER, AND I DON'T KNOW THE
OTHER PEOPLE ON THE DAIS, BUT
CAN YOU ACTUALLY HAVE INNOVATION
WITH LARGE COMPANIES WITH NIH
AND GOVERNMENT OR DOES IT HAVE
TO BE AN EMERGING STARTUP
COMPANY, AND IT'S ALMOST AN
EMOTIONAL QUESTION BECAUSE CAN
YOU MOVE THE INNOVATION ALONG
DEPENDING ON ITS TYPE AND TO THE
RIGHT SIDE, BRAD'S SIDE AND
PETER'D SIDE, WOULD YOU BE
CHERIE PICKING SOMETHING THAT
YOU THINK YOU CAN ACTUALLY
INNOVATE AND THEN MOVE QUICKLY
AND TRANSLATE IT INTO YOUR OWN
CLINICAL ENVIRONMENT FOR LIMITED
PATIENT WORK, AND THEN WHAT
WOULD YOU ACTUALLY WANT THEM TO
INNOVATE?
THAT'S SORT OF MY SOFTBALL
QUESTION.
>> OKAY.
>> LET ME START THIS OFF AND
THEN YOU GUYS CAN GO.
IT DEPENDS ON YOUR DEFINITION OF
INNOVATION AND I THINK THAT ALL
OF US HAVE SAID SOMETHING THAT'S
REALLY IMPORTANT, WHICH IS THIS
ECOSYSTEM IS INTERCONNECTED.
YOU SHOULDN'T TRY TO DO ALL OF
IT YOURSELF, AND I THINK THAT
MAY BE WHERE YOUR QUESTION WAS
GOING, IS THIS IDEA OF OKAY,
I'VE GOT TO TAKE IT ALL THE WAY
TO THE END.
NO, YOU'VE GOT PARTNERS ACROSS
SO MANY DIFFERENT INSTITUTIONS,
ORGANIZATIONS, YOU CAN BE SMALL,
LARGE, WHATEVER.
BUT UNDERSTAND WHERE YOUR
STRENGTH IS, AND THAT'S WHERE
YOU INNOVATE.
DON'T TRY TO INNOVATE ACROSS THE
WHOLE THING.
THAT'S WHERE PEOPLE USUALLY MAKE
THE MISTAKE, IS THEY HAVE THIS
ONE IDEA OF WHAT INNOVATION IS,
WHEN INNOVATION IS ABSOLUTELY
WHAT YOU WERE SAYING.
THERE ARE SO MANY CHANGES THAT
ARE GOING TO GO ALONG THE WAY.
THE FEEDBACK THAT YOU GET FROM
PATIENTS IS GOING TO MAKE YOU
TEAR UP ALL THE PLANS THAT YOU
HAD, AN SO YOU HAVE TO BE READY
FOR THAT.
AND THEN TO YOUR POINT ABOUT
NORTH CAROLINA, YOU KNOW THAT
THERE ARE GOING TO BE SOME
THINGS YOU DIDN'T EVEN
ANTICIPATE, SO YOU'RE GOING TO
HAVE TO BE ABLE TO PIVOT.
THAT IS INNOVATION.
BUT LET'S SEE IF OTHERS HAVE
THOUGHTS.
>> I THINK THERE ARE MANY
COMPANIES THAT ARE INNOVATING
AND THERE IS INNOVATION IN
COMPANIES.
IT DEPENDS, IT'S A LOADED
QUESTION.
IT DEPENDS ON THE COMPANY
CULTURE, DEPENDS ON THEIR
FINANCES, IT DEPENDS ON -- I
MEAN, IBM RESEARCH HAS 4,000
PEOPLE IN IBM RESEARCH AND
THEY'RE PUBLISHING VERY OPENLY
AP THEY'RE PUSHING QUANTUM
COMPUTING AND ALL OF THESE
THINGS, FOR EXAMPLE, SO I THINK
IT DEPENDS, BUT YOU CAN HAVE
INNOVATION IN LARGE COMPANIES.
THERE'S A LOT OF OTHER FACTORS
TO THAT.
THE OTHER I'LL TELL YOU, MANY OF
OUR ALUMS WHO HAVE BEEN VERY
SUCCESSFUL, IN MY JOB I GET TO
TALK TO LOTS OF ALUMS WHO WERE
STUDENTS, AND IT'S A GREAT PART
OF THE JOB.
ONE THING THAT I'VE LEARNED,
THOSE WHO ARE VERY SUCCESSFUL
NOW WHO STARTED COMPANIES,
ACTUALLY IT'S REALLY
INTERESTING, THEY ALL SAY NOW
THAT THEY WISH OR THEY'D HAD
THOSE THAT WERE SUCCESSFUL, THEY
HAD, OR THOSE THAT DIDN'T, THEY
SAID THEY WISHED THEY HAD GONE
AND WORKED FOR A COMPANY FIRST
RATHER THAN STARTING A COMPANY
STRAIGHT FROM SCHOOL.
THEY WISHED THEY HAD WORKED FOR
A FEW YEARS IN A COMPANY TO
LEARN HOW THINGS WORK, LEARN THE
PRACTICAL SIDE OF THINGS, LEARN
THE PROCESSES AND LEARN THE
BUSINESS PLANS AND LEARN ALL OF
THAT, AND THEN STARTED A
COMPANY.
AND MOST OF THE ONES THAT I MET
WERE HIGHLY SUCCESSFUL WERE THE
ONES THAT ACTUALLY WORKED AT A
BIG COMPANY FIRST, AND THEN
SPLIT OFF AND THEN WENT OFF AND
STARTED A COMPANY.
THERE'S CASES OF, OF COURSE,
STRAIGHT FROM SCHOOL AS WELL,
BUT IT'S INTERESTING, EACH QUN
ONEOF THEM, EVEN MYCO-FOUNDER N,
THE STUDENT THAT HAD DONE THIS
EIGHT YEARS, NINE YEARS, SAID I
WISH I WORKED AT A COMPANY SO IT
DIDN'T TAKE ME TO LONG TO LEARN
THESE THINGS.
>> I THINK INNOVATION IS
ADAPTATION, SO YOU CAN'T ASSUME
THAT THE CURRENT ECOSYSTEM AND
TREATMENTS ARE GOING TO STAND
STILL.
IT'S LIKE LANDING AN AIRPLANE ON
A RESOLVING EARTH THAT HAS A
CRUISER GOING AT A DIFFERENT
SPEED, YOU'RE PLAYING THE OLD
MOON LANDER VIDEO CAME.
IT'S A CHALLENGE, YOU'VE GOT TO
BE ADAPTIVE.
THERE'S SO MANY HURDLES TO
TRANSLATION AND ALL THE HURDLES
AND RATE LIMITING FEATURES
CHANGE OVER TIME.
SO JUST I AU BE ATTUNED TO THE
CHANGES AS THEY EVOLVE BECAUSE
THEY DEFINITELY WILL REDEFINE
YOUR PURPOSE, AND ASK DOES THIS
MODEL MAKE SENSE WITHIN WHATEVER
COMMERCIAL ENVIRONMENT YOU'RE
AIMING FOR, AND HAVING THE
COMMERCIAL AND THE BUSINESS
MODELS MATCH WITH THE CLINICAL
NEEDS, WITH THE TECHNOLOGY, IS
TOUGH.
AND YOU SHOULDN'T JUST DO IT
BECAUSE YOU CAN DO IT.
YOU'VE GOT TO DO IT WITH AN EYE
TO COST FROM THE START, WITH DAY
ONE.
WITH AN EYE TOWARDS THE
COST-EFFECTIVENESS.
BECAUSE IF YOU DON'T, YOU END UP
WITH A LOT OF COOL DEVICES, LIKE
WE HAVE NOW, THAT DON'T
NECESSARILY JUSTIFY THEIR
EXISTENCE.
AND YOU END UP COSTING THE
PUBLIC HEALTH OVERALL POCKET OF
RESOURCES THAT ARE AVAILABLE A
BIG COST, AND I'D SAY THE
DAVINCI ROBOT, WHILE IT'S COME A
LONG WAY, STARTED THAT WAY, WITH
BEING DRIVEN BY BILLBOARDS.
ALTHOUGH WE WORK WITH THEM NOW,
CLOSELY, AND IT CERTAINLY HAD AN
IMPACT.
BUT I WANTED TO SET HIM UP.
>> HOW ABOUT THIS, SO THE
QUESTION ABOUT STARTUPS AND BIG
COMPANIES, THAT'S A GOOD
QUESTION, STARTUPS AND BIG
COMPANIES.
YOU KNOW, I THINK IF YOU HAVE A
GOOD IDEA, THAT YOU FEEL A LARGE
COMPANY IS GOING TO BE A BIT
SLOW TO GET THROUGH THE PROCESS,
WHY IS THAT?
WELL, MAYBE BECAUSE THEY HAVE
OTHER FINANCIAL AGENDAS.
SO MAYBE THE STARTUP IS MORE
WILLING TO DO SO.
BUT I THINK YOU CAN TRY AS A
SCIENTIST TO PLEAD YOUR CASE
EVEN TO LARGE COMPANIES, AND
IT'S A LITTLE BIT LIKE A SALES
JOB.
YOU HAVE TO SELL THEM ON THE
FACT THAT THIS IS GOING TO FIT
IN THEIR PORTFOLIO.
AND WE CAME ACROSS A COMPETING
DEVICE, AS WE WERE GOING THROUGH
OUR NEW INNOVATION, THAT WE
DIDN'T KNOW WAS COMPETING IN THE
SAME FIELD.
THEY WERE ALREADY SELLING, WE
HAD TO CONVINCE THEM THIS WOULD
REPLACE THAT.
IT TOOK A LITTLE TIME.
SO THERE IS A PERSONALITY
INVOLVED BUT YOU HAVE TO KIND OF
PUSH ALONG, BUT BIG COMPANIES
ARE WONDERFUL TO PARTNER WITH,
AS LONG AS THEY FIT THE
PORTFOLIO.
>> ONE MORE AND THEN WE'LL GO TO
OUR NEXT QUESTION.
>> SO I'VE WORKED WITH SMALL AND
LARGE COMPANIES SUCCESSFULLY, AS
WELL AS NOT SO WELL.
I THINK WHAT IT COMES DOWN TO IS
JUST REMEMBER THAT IT'S REALLY A
PARTNERSHIP.
AND THE RELATIONSHIP AND YOUR
COUNTERPART ON THE OTHER SIDE IS
KEY.
I THINK -- SO YOU WANT TO LOOK
FOR AN OPEN PARTNERSHIP WHERE
THERE'S TRANSPARENCY, SHARING OF
IDEAS, FREE FLOW.
I DON'T CARE WHETHER IT'S A BIG
OR SMALL COMPANY, I THINK THOSE
ARE THINGS THAT YOU WOULD NEED
FOR ANY KIND OF INNOVATION AND
SUCCESS.
>> THANK YOU ALL.
ALL RIGHT.
PLEASE.
>> ON INNOVATION AT THE
INTERSECTION OF HEALTHCARE AND
RESEARCH DESERTS, AND SO
ASSUMING COST-EFFECTIVENESS,
LIMITATIONS LIKE COLD STORAGE,
THOSE ARE ALL FLAT, YOU DO SEE
COMING FROM THE RESEARCH SIDE
INTERACTING WITH CLINICIANS
WITHIN RESEARCH ESTABLISHMENTS
IN TERMS OF THINGS THAT MIGHT
NOT BE STANDARD OF CARE, THINGS
THAT MIGHT BE NEW, THAT'S GOING
TO BE A DIFFERENT INTERACTION
THAN, SAY, A CLINICIAN WITHIN A
SMALL FAMILY CLINIC IN A MORE
RURAL AREA.
SO UNDER THE ASSUMPTION THAT
COLD CHAIN, COST, ALL OF THOSE
THINGS ARE EQUAL, HOW DO YOU GO
ABOUT KIND OF BRIDGING THAT GAP
OF THAT RESEARCH ECOSYSTEM, OF
COURSE NOT BEING ABLE TO REACH
EVERYONE AND KIND OF PIGGY
BACKED ON THAT KIND OF
HEALTHCARE DESERT AS WELL?
>> WE WERE INNOVATING DURING THE
PROCEDURE TODAY AND IT RAN OVER,
SO IT WAS A NEW EXCITING
ENGINEERING DEVICE BUT IT COST
ME TIME AND I HAVE TO LEAVE NOW.
BUT I WILL SAY THIS.
I THINK THE RESEARCH ENVIRONMENT
FOR CLINICIANS, SCIENTISTS AND
INDUSTRY, IS WHERE YOU PUT THE
SEED FIRST.
AND LET THAT GERMINATE AND GROW
SOMETHING.
HAVING TRAINED COLLEAGUES,
TRAINED FELLOWS, RESIDENTS, WHO
ARE IN MORE OF A RURAL FAMILY
PRACTICE ENVIRONMENT, THE STRAIN
THEY'RE UNDER IS ENORMOUS.
FINANCIALLY, PATIENT CARE,
RESOURCES, AND, YOU KNOW,
CHILDREN DO WELL WHEN THEY'RE
LOVED AND CARED FOR.
AND WHEN THEY'RE UNDER ANXIETY,
WHERE IS THE NEXT MEAL COMING
FROM, MY MOM AND DAD DON'T LIVE
IN THE HOUSE ANYMORE, HOW DO YOU
GO TO SCHOOL?
SO I APPLY THAT TO THIS: THOSE
PHYSICIANS, YOU KNOW, THEY WANT
TO BE PART OF THE INNOVATION,
BUT TO GET IT STARTED, IT MAY BE
ALMOST TOO MUCH TO ASK THEM TO
DO ALL THEY'RE DOING FOR THOSE
PATIENTS WITH LIMITED RESTORES
OFTEN, AND FINANCIAL CONSTRAINTS
AND TO INNOVATE.
BUT WHEN YOU'RE FURTHER ALONG,
THEN YOU HAVE TO INCLUDE THEM
BECAUSE THAT'S REAL EVERYDAY
CLINICAL CARE, YOUR DEVICE MAY
CHANGE.
>> APPLICATION OF THE NEW
TECHNOLOGY IS NOT NECESSARILY
ADDING MORE WORK ON TO THAT, BUT
THINGS LIKE HAVING CONVERSATIONS
WHERE, SAY, TREATMENT X COULD BE
CONSIDERED STANDARD OF CARE AT A
CLINIC, THAT'S MORE
RESEARCH-BASED, BUT IN SPEAKING
WITH SOMEWHERE THAT'S A BIT MORE
IN A HEALTHCARE RESEARCH DESERT,
THAT SORT OF THING, BUT
CERTAINLY THE BANDWIDTH ISSUE IS
MASSIVE.
>> RIGHT, WELL, THEN YOU THINK
ABOUT YOUR CLINICIAN-SCIENTISTS
YOU'RE WORKING WITH.
IF THAT PERSON IS ON PANELS,
GUIDELINE COMMITTEES, YOU KNOW,
DOES HE HAVE A POSITION IN HIS
FIELD, THAT YOU KNOW THAT PERSON
HAS THAT KNOWLEDGE BASE.
IF YOU HAVE A PERSON WHO IS A
CLINICIAN BUT HASN'T SEEN A
PATIENT FOR 20 YEARS, IS IN THAT
DEEP PART OF THE BASEMENT, MAYBE
THAT'S NOT THE BEST PERSON TO
START WITH.
SORRY I HAVE TO LEAVE,
EVERYBODY.
>> THANK YOU.
DID ANYONE ELSE WANT TO ADDRESS
IT?
>> I WAS JUST GOING TO SAY, IT
GOES BACK TO THE QUESTION
EARLIER.
THINK ABOUT THE LANE WHERE YOU
CAN HAVE THE MOST IMPACT.
THIS IS A CONVERSATION I'VE HAD
IN MASSACHUSETTS FOR A NUMBER OF
YEARS, THIS IDEA THAT A LOT OF
PEOPLE TRY TO BE IN CAMBRIDGE,
BUT THERE'S SO MUCH GOING ON IN
WESTERN MASS AND ALL THAT, THAT
IT'S JUST AS IMPORTANT AND GUESS
WHAT, THE PEOPLE IN CAMBRIDGE
DON'T THINK THE SAME WAY AS IN
WESTERN MASS.
SO DON'T THINK ABOUT TRYING TO
GET IT INTO A CLINIC, BUT THINK
ABOUT ALL OF THE PRE-CLINICAL
STUFF THAT HAS TO BE DONE.
THAT'S WHERE THAT GROUP THAT
YOU'RE TALKING ABOUT IS GOING TO
BE THE MOST POWERFUL.
THEY'RE PROBABLY GOING TO ALSO
BE THE ONES MORE LIKELY TO COME
UP WITH A DIAGNOSTIC.
THE CAMBRIDGE PEOPLE ARE NOT
GOING TO BE DOING THAT.
>> QUICK POINT.
ICOR IS A GREAT PROGRAM OR
PROGRAMS LIKE IT WHERE YOU LACK
AT THE DIFFERENT STAKEHOLDERS
AND LOOK AT HOW DOES THE MODEL
APPLY TO A SPECIFIC NEED WITH
THE EYE OF THE STAKEHOLDER,
CONSUMER, PROFESSIONAL
CLINICIAN, WHATEVER IT IS, IT'S
GOOD FOR FOLKS STARTING OUT.
THE OTHER IS DON'T BE AFRAID TO
REDRESS, PUT SOME LIPSTICK ON
THE PIG, SO TO SPEAK.
I THINK LOTS OF TECHNOLOGIES
INCLUDING SOME WE'VE HAD
EXPERIENCE WITH GET IN THE
CLINIC IN A ROUNDABOUT WAY, NOT
IN THEIR INTENDED USE, IN A
BYSTANDER CLINICAL STUDY OR IN A
WAY THAT HAS NOTHING TO DO WITH
HOW YOU REALLY THINK IT'S GOING
TO IMPACT THINGS.
DON'T BE AFRAID -- IT'S
COMPLIANT, IT'S LEGAL, DON'T BE
AFRAID TO THINK DIFFERENTLY
ABOUT IT.
>> PUT LIPSTICK ON THE PIG.
I LIKE THAT.
THANK YOU.
YES, PLEASE.
>> GOOD AFTERNOON.
MY NAME IS LEA, I'M FROM THE
NATIONAL CENTER FOR ADVANCING
TRANSLATIONAL SCIENCES, SO I'M
PART OF NIH.
I'M A PROGRAM OFFICER, AND THIS
QUESTION IS FOR CHERIE.
YOU SAID MANUFACTURING IS A
BOTTLENECK FOR THERAPEUTICS OR
DEVICES TO REACH THE PATIENT.
HOW TO YOU FIT A PICTURE, NIH
HELPING IN THIS PARTICULAR
ASPECT?
BECAUSE NIH IS MAINLY BASIC
SCIENCE, RIGHT?
WELL, EXCEPT FOR NCATS, MY
INSTITUTE.
BUT HOW DO YOU SEE THAT?
HOW CAN NIH HELP?
>> SO I FEEL LIKE THIS IS A
PLANTED QUESTION BECAUSE I'VE
BEEN WAITING MY WHOLE LIFE TO
ANSWER THIS ONE.
>> I DIDN'T KNOW YOU BEFORE
THIS.
JUST TO BE CLEAR.
>> SO I'M GOING TO TALK ABOUT
NCATS BUT I THINK THIS IS TRUE
FOR ALL OF THE NIH CENTERS.
WHEN WE'RE -- AND THIS GOES BACK
TO THE OTHER QUESTION FROM
BEFORE.
LET'S TALK ABOUT RARE DISEASES.
WE DON'T KNOW ANYTHING ABOUT THE
NATURAL HISTORY, SO AS WE'RE
DEVELOPING A THERAPY, WE DON'T
REALLY KNOW WHICH VERSION
BECAUSE THEY'RE ALL
HETEROGENEOUS.
YOU GUYS ARE MASTERS, YOU GUYS
ARE REALLY PUTTING TOGETHER THE
NATURAL HISTORY STUDY STORY.
THAT'S ONE VERSION.
THE OTHER PART ABOUT RARE
DISEASES IS THEY'RE EXTREMELY
HETEROGENEOUS EACH ONE OF
THEMSELVES.
AND WHAT'S INTERESTING ABOUT
WHAT NCATS HAS BEEN DOING IS
THEY'RE TAKING A STEP BACK AND
SAYING, RATHER THAN US LOOKING
AT THE HETEROGENEITY OF EACH
DISEASE, WHY DON'T WE LOOK AT
THE SIMILARITIES ACROSS THESE
DISEASES.
WHERE CERTAIN PATIENT PROFILES
ACTUALLY LOOK VERY SIMILAR, AND
GUESS WHAT THAT DOES?
THAT GIVES LINE OF SIGHT TO
MAYBE CERTAIN THERAPIES THAT
WERE TARGETED TO ONE DISEASE
COULD ACTUALLY BE TARGETED TO A
WHOLE SERIES OF THEM.
SO THE WORK YOU GUYS ARE DOING
IS SO IMPORTANT.
AND THEN EACH OF THESE
INSTITUTES AND CENTERS, THEY'RE
REALLY PROVIDING THE FOUNDATION
TO WHAT INDUSTRY CAN BE DOING.
IN TERMS OF THE MANUFACTURING,
LET ME BE CAREFUL ABOUT THAT.
IT'S THE APPROVAL PROCESS.
IF YOU CANNOT PROVE THAT YOU CAN
MANUFACTURE ENOUGH FOR EVERYONE
WHO HAS IT, GUESS WHAT IT'S
GOING TO CREATE?
A SUPPLY AND DEMAND PROBLEM.
SO PART OF THE APPROVAL PROCESS
IS PROVING THAT YOU CAN MAKE
ENOUGH AND THAT THERE IS A PLAN
IN ORDER TO ACCESS IT, AND
SOMETIMES COMPANIES COME AND
THEY DIDN'T HAVE THAT SO THEY
WOULDN'T GET APPROVAL.
SO I DO WANT TO BE CAREFUL ABOUT
THE MANUFACTURING PART.
BUT NIH IS REALLY, REALLY
CRITICAL.
NOW THAT I'VE BEEN IN INDUSTRY,
I KNOW HOW MUCH MORE CRITICAL
THEY ARE.
>> WE'RE TRYING TO ADDRESS THE
MINUSCULE AMOUNTS OF NATURAL
PRODUCTS YOU CAN GET FROM PLANTS
AND TRYING TO MAKE MORE OF IT,
THE SAME WITH BIOLOGICS.
SO WE'RE ACTUALLY ON TO THAT.
RIGHT NOW AT NCATS.
THANK YOU.
>> GREAT.
THANK YOU VERY MUCH.
WE HAVE ANOTHER QUESTION HERE.
>> MY QUESTION IS PROBABLY
CASE-BASED, SO I AM STARTING A
COMPANY WITH ONE OF MY STUDENTS,
AND ANOTHER STUDENT IN MY LAB
WITH THE OTHER TECHNOLOGY, HE'S
ALSO VERY EXCITED ABOUT THIS AND
WANTS TO START A COMPANY TOO,
AND HOW ORGANIC THIS PROCESS WAS
FOR YOU, DR. BESHEAR, YOU KNOW,
IS IT -- YOU 1/2 GATED AND HOW
DID YOU DECIDE, LIKE, WHO
OWNS -- I JUST WANT TO HEAR YOUR
THOUGHTS ABOUT THIS FIRST.
>> I CAN SAY A FEW THINGS AND
I'M HAPPY TO TALK OFFLINE, BUT I
THINK I DID ONE AT A TIME,
THOUGH.
SO I DIDN'T DO TWO AT A TIME, I
DID ONE AT A TIME.
BUT THAT'S OKAY, THIS IS GREAT.
YOU CAN DO IT.
BUT I THINK WHAT'S REALLY
IMPORTANT IS THAT -- I MEAN, THE
STUDENT HAS TO BE THE RIGHT
STUDENT ALSO.
HAS TO BE THE RIGHT PERSON.
I'VE HAD SITUATIONS WHERE A
PERSON -- I MEAN, I KNEW THAT
THEY WERE PERHAPS NOT THE RIGHT
PERSON AND IT'S NOT DISCOURAGING
THEM IN WHAT THEY WANT TO DO,
BUT IT'S JUST THAT IDENTIFYING
HOW TO BUILD THE RIGHT TEAM AND
THEN PERHAPS THEY NEEDED TO
COMPLEMENT WHAT THEY HAD WITH
SOMEBODY ELSE TO BUILD A TEAM.
SO I THINK THAT'S REALLY
IMPORTANT TO GET -- HAVE PEOPLE
THINK THROUGH THAT, AND
SECONDLY, I THINK THERE WAS THIS
MODEL YEARS AGO WHERE FACULTY
THOUGHT AND STILL THINK, MANY OF
THEM, THAT THEY OWN A BIG PART
OF -- THAT THEY SHOULD HAVE A
BIG PART OF THE EQUITY IN THE
COMPANY BECAUSE --
>> OF COURSE WE SHOULD!
WHY ARE WE WRONG?
>> BECAUSE IT CAME OUT OF THEIR
LAB, BUT THE REALITY IS THAT THE
AMOUNT OF WORK THAT IT TAKES
FROM THAT TIME TO REALLY MAKE IT
SUCCESSFUL UNLESS YOU ARE GOING
TO LEAVE YOUR JOB AND GO JOIN OR
SPEND A LOT OF TIME, IT IS MORE
IMPORTANT TO GIVE MORE EQUITY
AND MORE OWNERSHIP TO THE
STUDENTS.
AND TO THE OTHER CO-FOUNDER
WHO'S GOING TO DEDICATE HER OR
HIS LIFE TO THAT FOR THE NEXT 10
YEARS OR FIVE YEARS.
SO I THINK THERE'S A LOT OF
NUANCES THERE WE CAN DISCUSS,
BUT I MEAN, THE FACT IS AT THE
END OF THE DAY, EVEN THOUGH I
SAID EARLIER THAT WE WANT
STUDENTS TO HAVE SOME EXPERIENCE
AND THEN START A COMPANY, AT THE
END OF THE DAY, PEOPLE SHOULD
FOLLOW THEIR PASSION.
THEY HAVE TO FOLLOW THEIR
PASSION, AND OF COURSE THE
PASSION NEEDS TO BE TUNED IN
WITH SOME REALITY, EXPERIENCE,
ADVICE AND BUILD THE TIME AND
ALL OF THOSE THINGS, BUT I THINK
IT'S REALLY IMPORTANT TO EMPOWER
THE STUDENTS AND SUPPORT THEM,
SO I SUPPORTED, ADVISED FOR A
LONG TIME, BUT I NEVER JUMPED
SHIPS COMPLETELY FOR A LONG
PERIOD OF TIME.
THAT WAS ON THEM, AND HENCE,
THEY DO NEED TO BE EMPOWERED
MORE AND, HENCE, REWARDED MORE.
>> THANK YOU SO MUCH.
YOU ANSWERED MY QUESTION.
THE OTHER QUESTION IS ABOUT
TECHNOLOGY READINESS LEVELS,
BECAUSE I THINK AS THE COMMITTEE
HERE, ALL OF YOU MENTIONED
SIMILAR THINGS LIKE HOW DO YOU
DECIDE A TECHNOLOGY IS -- LIKE
HOW DO YOU FEEL IT, MAYBE IT
WOULD BE A GOOD SUCCESS FOR A
PRODUCT BECAUSE WE ALL THINK
THAT OUR INVENTIONS ARE GREAT.
>> I THINK THAT'S A GREAT
QUESTION.
WHEN DO YOU KNOW IT'S REDI TO GO
GO TO A COMPANY?
>> BECAUSE EUROPE HAS TRLLs
BUT I DON'T KNOW IF IN THE
UNITED STATES FDA HAS SOME SORT
OF CLASSIFICATIONS FOR TRLs.
>> AND JUST WHEN DO YOU KNOW
THAT THE TECHNOLOGY IS READY?
>> SO SOMETHING WHEN I WAS A
STUDENT AT HOPKINS, THEY
ACTUALLY HAD ME DO THIS TO
ANSWER THIS QUESTION, WHICH WAS
BASICALLY MARKET RESEARCH, LIKE
WHAT'S THE NEED, IS ANYBODY
GOING TO BUY IT?
YOU SHOULD BE DOING THAT.
IN INDUSTRY, WE CALL IT
COMPETITIVE INTELLIGENCE, BUT I
MEAN, YOU'VE GOT TO BE ABLE TO
PROVE, TO THE POINT EARLIER
ABOUT PITCHING THIS IDEA AND
GETTING SUPPORT TO ADVANCE IT --
>> IF IT'S JUST GOING TO CHANGE
LIVES?
IS THAT NOT SUFFICIENT?
LIKE YOU KNOW IT'S A HUGE
ADVANCE FORWARD.
>> NO, NO, NO, NO.
>> I THINK THAT'S WHAT A LOT OF
US THINK, THEN YOU SAY DO MARKET
RESEARCH, LIKE SAVING LIVES IS A
GREAT REASON THIS WILL MAKE
MONEY.
>> THAT IS A CATCH PHRASE.
>> DEFINITELY I CORE HELPS.
WE DID 2ICORs --
>> WE'RE GOING TO HAVE TO MOVE
OVER TO THE NEXT QUESTION.
DID ANYONE ELSE WANT TO ADDRESS
THE FIRST PART?
>> THE TRL LEVELS ARE VERY
WELL-DEFINED BY DARPA OR DOD.
>> WHEN YOU EXPLAIN WHAT TRL IS?
>> A TECHNOLOGY READINESS LEVEL.
SO IT'S VERY WELL-DEFINED
ACTUALLY.
SO I THINK -- YEAH, YOU CAN
JUDGE AGAINST THAT.
BUT YOU CAN ALSO SEE WHEN YOU'RE
READY.
I THINK THE INVESTORS WILL TELL
YOU WHEN THEY'RE LOOKING TO PUT
SOME MONEY IN, THEY'LL TELL YOU,
NOT READY, OR READY TOO.
OVER THERE, PLEASE.
>> HI.
I'M A PH.D. CANDIDATE AT THE
UNIVERSITY OF SOUTHERN
CALIFORNIA.
THIS IS KIND OF A DIRECT
FOLLOW-UP TO HER FIRST QUESTION.
AS A PH.D. STUDENT, I NOTICED
THAT WE KNOW THAT THE MEDICAL
FIELD IS VERY INTERDISCIPLINARY,
BUT I THINK THAT A LOT OF GATE
KEEPING COMES FROM PEOPLE
WANTING TO PROTECT LIKE THEIR
INTELLECTUAL PROPERTY AND THINGS
LIKE THAT, ESPECIALLY FROM YOU
WHO SAY YOU COLLABORATED WITH
YOUR STUDENTS.
WHAT PROTECTIVE MEASURES ARE
THERE, AND MAYBE IN INDUSTRY OR
NIH, THAT PROTECT THE INDIVIDUAL
RESEARCHER'S IDEA, LIKE DO THEY
HAVE ANY MOTIVATION TO DO THAT
BECAUSE LIKE YOU SAID, IF YOU'RE
USING THEIR RESOURCES,
TECHNICALLY THEY DO HAVE A
SAY-SO.
ARE THERE ANY PROTECTIVE
MEASURES OR HOW DO YOU NAVIGATE
THAT TO PROTECT YOURSELF?
>> INTERESTING.
>> THAT'S A GREAT QUESTION.
I THINK THERE'S A LOT OF SYSTEMS
OUT THERE, DEPENDING ON YOUR
INFRASTRUCTURE, ACADEMICS IS
DIFFERENT THAN GOVERNMENT,
THEY'RE ALL REQUEST GOING TO HAY
TIGHT CONFLICT OF INTEREST RULES
THAT'S IMPORTANT TO KNOW ABOUT
AND FOLLOW AND KNOW BEFOREHAND.
MANY PLACES LIKE OXFORD WILL
HAVE INCUBATORS WHERE PROFESSORS
WORK HALF A DAY A WEEK ON A
CERTAIN COMPANY, THEY HAVE THE
COMPANY SEPARATE FROM THE
UNIVERSITY AND THAT'S TOTALLY
ACCEPTABLE AND ETHICAL.
IT DEPENDS ON THE LOCAL CULTURE.
SO YOU'VE GOT TO REALLY CHECK
OUT YOUR LOCAL CULTURE, FIND OUT
WHAT'S NEEDED.
ALSO NOT JUST STAYING WITHIN THE
GUARDRAILS, BUT THE MOTIVATION
TO PROTECT.
WHAT ARE YOU PROTECTING FROM IS
THE QUESTION.
IF YOU'RE REALLY PROTECTING
SOMETHING THAT'S AMAZING AND
YOU'VE RELIED ON A YEAR OF YOUR
WORK TO FIND OUT SOMETHING NO
ONE ELSE KNOWS, OKAY, THAT'S ONE
THING.
IF IT'S AN IDEA YOU HAD, MANY
PEOPLE FAIL IN THIS UP-FRONT
THING AND THEY THINK OF AN IDEA
AS BEING OWNED AND OWNERSHIP AND
HOW AM I GOING TO BE PROTECTED
BECAUSE IT'S A COOL IDEA, IT'S
MY IDEA.
THE "MY IDEA" CONCEPT DESTROYS A
LOT OF INNOVATION.
IT DESTROYS INNOVATION.
AND I'M NOT SAYING -- THERE'S
MANY PROTECTIVE MEASURES THAT
ARE NEEDED BUT 95% OF THEM ARE
NOT NEEDED AND WOULD ACTUALLY,
YOU KNOW, SQUELCH THE INNOVATION
AND SQUELCH THE POSSIBLE IT'S
ACTUALLY GOING TO END UP
SOMEWHERE.
SO YOU'VE GOT TO BE CAREFUL WHAT
YOU DO.
THAT DOESN'T MEAN YOU CAN'T BE
PASSIONATE ABOUT IT AND YOU'VE
GOT TO PATENT TO GET IT DOWN THE
ROAD.
COMPANIES VALUE THAT.
IF THEY HAVE AN IP PROTECTION IN
A TECHNOLOGY THAT WE'RE TAKING
TO THEM, THEY JUMP ON IT MUCH
QUICKER THAN IF YOU JUST SAY
I'VE GOT AN IDEA, WE FILED A
LITTLE SOMETHING OR I'VE GOT AN
IDEA, THEN YOU'RE GIVING TO
THEM.
SO IT JUST DEPENDS.
>> I MEAN, I THINK WE CAN HAVE A
WHOLE 45-MINUTE DISCUSSION ON
THIS.
MY IDEA BEING A BAD WAY OF
FRAMING IT.
THAT'S -- I THANK YOU FOR THAT
QUESTION.
I FIND THAT FASCINATING.
OKAY.
WE'RE GO TO GO TO -- THIS MIGHT
BE OUR FINAL QUESTION.
PLEASE, GO FOR IT.
WOW, THAT'S INTERESTING.
SORRY.
>> HELLO.
I'M A GRADUATE STUDENT FROM
PURDUE AND MY QUESTION IS
DIRECTED TO DR. WOOD.
SO WHAT WOULD IT TAKE FOR YOU TO
TRUST A COMPUTATIONAL MODEL
PREDICTION OVER YOUR GUT
FEELING?
LIKE LET'S SAY THERE'S A MODEL
THAT CAN PREDICT THE
CIRCUMFERENCE OF A TUMOR AND
THEN WHAT WOULD IT TAKE FOR A
SURGEON TO TRUST THE MODEL
PREDICTION OR WHAT YOU FEEL BY
LOOKING AT THE IMAGES?
>> THAT'S A GOOD ONE.
>> LOOK, I MEAN, I TRUST FACTS,
AND WEEK BEFORE AN ELECTION, I'M
GOING TO AVOID ANY POLITICAL
STATEMENTS, BUT, YOU KNOW, THE
FACTS TELL THE STORY.
AND IF AN AI BLACK BOX MODEL
DELIVERS THE GOODS TO ME, I'M
ALL IN.
BUT YOU'VE GOT TO KNOW WHAT THE
LEVELS OF EVIDENCE ARE MIND IT.
95% OF THE LITERATURE IS
MISLEADING AT BEST, AND
SOMETIMES FRANKLY FALSE.
SO WE ALL GET REWARDED FOR
PUTTING OUT OUR BEST STUFF AND
POSITIVE P VALUES, ET CETERA,
DOWN THE ROAD, THAT'S HOW WE GET
TO OUR NEXT COMPANY, AND AT THE
END OF THE DAY, THOSE INCENTIVES
LEAD TO A BIG SMORGASBORD OF
LESS THAN HELPFUL INFORMATION.
>> SO LET ME CHALLENGE YOU,
BRAD.
>> INCREDIBLE LEVELS OF --
>> YOU SAY YOU TRUST THE A.I.
FROM THE FACTS BUT THAT'S YOU,
BECAUSE YOU'RE WORKING IN A
TRAPS LAITIONAL SPACE.
WHAT ABOUT THE REST OF YOUR
SURGICAL COLLEAGUES?
ARE THEY GOING TO TRUST THESE
THINGS AS YOU MIGHT?
AND WHAT CONVINCING MIGHT THEY
NEED?
>> LOOK BELOW THE HOOD, YOU HAVE
TO REACH OUT TO YOUR DATA
SCIENTISTS IN THE SETTING OF
A.I. OR UNDERSTAND THAT IF IT
DOESN'T HAVE CONTINUOUS LEARNING
BUILT INTO IT AND PROTECTION OF
PRIVACY, WHICH ALSO KILLS A
BUNCH OF GOOD IDEAS, YOU'RE IN
TROUBLE.
SO YOU KNOW, MY ANSWER IS
FLIPPED, BUT YOU HAVE TO JUST
LOOK UNDER THE HOOD.
THERE'S NO SHORTCUT TO TRYING TO
DIVE DEEP AND ASK THE HARD
QUESTIONS THAT MAKE SOMETHING
FAIL.
AND THINK OF WHY IT GOING TO
FAIL FIRST.
AND I'LL BELIEVE IT AT THE END
OF THE DAY IF I'VE BEEN REALLY
CURIOUS ABOUT IT AND ASKED SOME
TOUGH QUESTIONS UP FRONT OF THE
PEOPLE THAT MIGHT KNOW OR
MYSELF.
AND MORE IMPORTANT, YOURSELF.
GO TO THE LITERATURE YOURSELF,
LOOK IT UP YOURSELF.
LEARN SOMETHING ABOUT ANOTHER
DISCIPLINE YOURSELF.
THAT'S THE BEST WAY IF YOU'RE
STARTING A COMPANY TO DEAL WITH
IT.
>> DR. BASHIR WANTS TO RESPOND,
I'M GOING TO ASK THE REST OF YOU
TO THINK OF A ONE MINUTE
RESPONSE TO WHERE DO YOU GET
YOUR INNOVATION FROM.
>> I WAS JUST GOING TO ADD TO
THE QUESTION AND ASK YOU A
QUESTION, IS THAT I MEAN,
SURGEONS ARE ALSO VERY BUSY.
SO THEY DON'T HAVE THE TIME TO
GO LOOK FOR STUFF, SO WHO DO YOU
TRUST OR HOW DO YOU TALK -- WHO
DO YOU TALK TO TO SAY OKAY,
YEAH, THIS MAKES SENSE VERSUS
THIS DOESN'T?
THAT'S WHAT SHE'S ASKING, I
THINK.
>> I'LL ANSWER MY ONE MINUTE
WITH THAT ANSWER, WHICH IS I
REACH OUT TO PEOPLE WHO I
RESPECT AND WHO HAVE ALREADY
PASSED THE MUSTER IN MY OWN MIND
OF WHAT THEIR OPINION MIGHT
LEAD.
SO I LOOK LIKE I'M LAID BACK AND
RELAXED AND I'M CONSTANTLY
JUDGING LEVELS OF INFORMATION
AND MAYBE THE LEVELS OF
INFORMATION ARE BEING FED TO ME,
SO YOU HAVE TO DO THAT TO
SURVIVE.
AND SO I THINK ONE WHAT AM I
PASSIONATE ABOUT, DO I GET
EXCITED ABOUT INNOVATION?
IT'S THE TRAINEES AND THE FACT I
CAN COME TO WORK EVERY DAY AND
LEARN SOMETHING NEW FROM A
DIFFERENT DISCIPLINE OR FROM
SOME YOUNG UNFETTERED MIND WHO
HASN'T BEEN TUNNEL VISIONED WITH
THE TRAINING THEY'RE GOING TO
RECEIVE YET, WHICH IS MANY OF
YOU ALL, AND THE FUTURE TITLES
AND THE 10 TOUR, TENURE, IT'S L
IT'S CRACKED UP TO HE BE.
YOU'VE GOT TO CONSTANTLY
STRUGGLE TO REMAIN OPEN MINDED,
THAT'S A LIFELONG STRUGGLE AND
IT BEGINS TODAY.
BUT BEING IN A TRAINING
ENVIRONMENT, LEARNING FROM THE
TRAINEES, LEARNING FROM OTHERS
IN OTHER DISCIPLINES, THAT'S THE
PURE PASSION OF INNOVATION.
>> HATE TO CUT YOU OFF, THANK
YOU.
VIN SERNGHTS YOU'VE GOT ONE
MINUTE.
VINCENT, ONE MINUTE, INNOVATION,
WHERE DO YOU GET IT FROM.
>> I'VE GOT TO AGREE WITH BRAD,
IT REALLY IS THE STUDENTS, THE
TRAINEES AND THE YOUNGER FACULTY
MEMBERS, WHERE THEY'RE --
>> OLD FACULTY CAN BE HELPFUL.
>> WELL, YOU KNOW, THEY ASK
QUESTIONS THAT USUALLY ARE
UNORTHODOX OR KIND OF THE
INNOCENCE, WHY DON'T WE DO THIS,
AND YOU'RE RIGHT, YOU'RE RIGHT.
BUT IT ALSO THOSE AHA MOMENTS.
YOU KNOW, WHERE YOU SAY OH, WOW.
IT WAS THAT SIMPLE.
>> AHA, EUREKA.
>> THAT REALLY DROPS YOU.
BUT I THINK IT'S THE TRAINEES
AND THE TEACHING ENVIRONMENT.
>> THAT'S GREAT.
CHERIE, ONE MINUTE.
WHAT YOU GOT?
INNOVATION.
>> AS ONE WHO DOESN'T HAVE
ACCESS TO TRAINEES IN A TEACHING
ENVIRONMENT, I ACTUALLY FIND
INNOVATION IN GETTING OUT OF THE
LAB AND GETTING OUT OF CLINIC,
AND LISTENING TO PEOPLE, REGULAR
PEOPLE AND SOME OF THE THINGS
THAT THEY RAISE, AND THAT ALWAYS
CONNECTS SOMEHOW RANDOMLY TO THE
WORK THAT I'M DOING, SO I
ACTUALLY PREFER TO BE OUTSIDE,
PREFER TO BE AMONG WHAT I CALL
REGULAR PEOPLE BECAUSE I THINK
THAT'S WHERE ALL OF THE IDEAS
REALLY START TO SPARK, BECAUSE I
HADN'T THOUGHT OF THAT.
AND THIS GOES BACK TO YOUR POINT
ABOUT NORTH CAROLINA.
THE STRUGGLES, THEY'RE GOING TO
HAVE TO BE INNOVATIVE TO
SURVIVE, AND THAT IS PROBABLY
WHERE SOME OF THE BEST IDEAS FOR
WHAT WE DO WILL COME FROM.
>> THAT'S GREAT.
ALL RIGHT.
DR. BASHIR, CLOSE US OUT.
ONE MINUTE.
INNOVATION, WHERE DO YOU GET IT
FROM?
>> I THINK IT'S ALL THE USUAL,
THE ECOSYSTEM AROUND YOUR
STUDENTS, COLLEAGUES,
COLLABORATORS, PAPERS, BUT I
THINK PUSHING, PUTTING YOURSELF
IN REALLY UNUSUAL SITUATIONS AND
OUT OF THE BOX, MAKING A POINT
TO TRY TO BE OUT OF THE BOX, GO
VISIT OUT OF THE BOX PLACES AND
PEOPLE, IT'S REALLY IMPORTANT.
I PURPOSEFULLY TRY TO DO THAT,
AND I THINK THAT'S WHERE I
BELIEVE A LOT OF THE INNOVATION
CAN COME FROM.
TO REALLY GO OUT OF THE BOX, SO
YOUR BUILT ECOSYSTEM IS GREAT
BUT YOU'VE GOT TO KEEP GOING OUT
OF IT FOR SOME PERCENT OF YOUR
TIME.
>> I WANT TO THANK YOU ALL FOR
ATTENDING AND THANK OUR
PANELISTS, ROUND OF APPLAUSE FOR
THEM.
IF YOU HAVE A RAPID FIRE
PRESENTATION, CAN YOU MAKE IT UP
HERE TO THE FRONT LEFT AND WE
WILL GET STARTED ON THOSE.
AGAIN, THANKS AGAIN.
>> THANKS TO MANU, WHO'S DONE AN
AMAZING JOB AT THIS MEETING.
>> THANK YOU.
>> OKAY, SO WE ARE BACK WITH OUR
RAPID FIRES, SIX MO MORE RAPID
FIRES AND WE WILL START WITH OUR
FIRST ONE, ANEESH KSHIRSAGAR.
>> HELLO, I'M ANEESH, A PH.D.
STUDENT AT PENN STATE AND OUR
GROUP MAINLY FOCUSES ON POINT OF
CARE DIAGNOSTICS, ENGINEERING
ASPECT FOR INFECTIOUS DISEASES.
TODAY I'M GOING TO TALK ABOUT
SALIVA BASED DETECTION OF TRIPLE
RESPIRATORY VIRUSES WITH
MULTIPLEXED RT-LAMP ON A MACHINE
LEARNING EMPOWERED PORTABLE
SYSTEM.
I'D LIKE TO ACKNOWLEDGE OUR
FUNDING SYSTEMS AT THE BOTTOM.
SO 40% OF U.S. HOSE HOLDS WERE
AFFECTED BY RESPIRATORY
INFECTIONS, EITHER OF COVID-19
INFLUENZA OR RSV.
IN 22-23 WINTER SEASON.
AND OTHER STUDIES HAVE SUGGESTED
THAT THAT COULD BE UP TO 15 TO
20% INCREASE IN HOSPITALIZATION
RATES, WHEN COINFECTIONS ARE
PRESENT.
THESE INFECTIONS SHOW VERY
SIMILAR SYMPTOMS WHICH MAKES THE
DIAGNOSTICS SOMETIMES
CHALLENGING.
AND INDEED THERE ARE DIFFERENT
ANTIVIRAL TREATMENTS AVAILABLE
FOR THESE, BUT IT REQUIRES
TIMELY AND ACCURATE DIAGNOSTICS
TO MEET THE TIME CRITICAL
WINDOWS.
TREATMENT WINDOWS.
ESPECIALLY FOR HIGH RISK GROUPS.
THE CURRENT DIAGNOSTICS INCLUDE
NASAL OR NASOPHARYNGEAL SWAB
BASED TESTS USING PCR, SO
THERE'S A LACK OF LOW COST
NONINVASIVE RAPID DIAGNOSTIC
TEST THAT IS CAPABLE OF LOOKING
AT ALL THESE DIFFERENT PATHOGENS
IN A SINGLE TEST, AND FOR WHICH
THERE IS AN URGENT NEED FOR
POINT OF CARE SOLUTIONS TO
ENABLE REALTIME AND MULTIPLEX
DETECTION IN A TIMELY MANNER.
SO OUR PROJECT HERE OR OUR
RESEARCH HERE USES A NONINVASIVE
MULTIPLEX DIAGNOSTIC SOLUTION
THAT ESSENTIA ESSENTIALLY USES A
SAMPLE, IT'S AN ISOTHERMAL ASSAY
THAT USES DARK WHICH STANDS FOR
DETECTION OF AMPLIFICATION BY --
QUENCHING METHOD TO LOOK AT
SPECIFIC TARGETS.
ALL OF THIS REACTION IS RUN ON A
PORTABLE INSTRUMENT POWERED BY
MACHINE LEARNING.
I'LL WALK YOU THROUGH THE DESIGN
OF THIS ANALYZER.
SO WE HAVE A COMPACT AND
PORTABLE BATTERY-OPERATED
ANALYZER THAT CAN RUN EIGHT
REACTIONS IN PARALLEL AND TO
FOCUS ON THE OPTIC SYSTEM FOR
THAT MULTIPLEXED FLOW FOR
DETECTION WE HAVE A WAVE LENGTH
L.E.D. AS THE EXCITATION SOURCE
AND CMOS SENSOR THAT'S A
MULTI-SPECTRAL SENSOR THAT CAN
LOOK AT EIGHT DIFFERENT
CHANNELS.
THERE'S CHALLENGES IN ASSEMBLY.
SO THE SENSING PRINCIPLE IS VERY
SIMPLE.
WE JUST EXCITE EACH OF THESE
SOURCES ONE BY ONE, AND LOOK AT
THE COLLECTIVE EMISSIONS FROM A
MIXTURE ACROSS DIFFERENT
CHANNELS OF THE SENSOR.
THIS GIVES RISE TO 24 DIFFERENT
VALUES SO HOW DO WE MAKE USE OF
ALL OF THIS INFORMATION?
WE DECIDED TO USE MACHINE
LEARNING HERE WHERE WE FIRST
COLLECT TRAINING AND TEST
DATASET USING CALIBRATION
EXPERIMENTS, WHERE WE LOOK AT
DIFFERENT SAMPLES OR MIXTURES OF
SAMPLES THAT ARE PREPARED FROM
DIFFERENT CONCENTRATIONS OF
DIFFERENT FLUOROPHORES.
NEURAL NETWORKS PERFORM THE BEST
AS EVIDENT FROM THE LEAST MEAN
ABSOLUTE AND THIS IS WHAT IS
CHOSEN MOVING FORWARD.
THIS IS A VERY VERSATILE AND
ADAPT TAABLE SYSTEM BECAUSE THES
NO FILTERS WE CAN EASILY RETRAIN
THE MODEL TO LOOK AT DIFFERENT
FLUOROPHORES SO HOW DOES THIS
ANALYZER PERFORM?
FIRST WE LOOKED AT SIMPLE RNA
COMBINATIONS WHERE FROM THREE
DIFFERENT TARGETS, WE COULD MAKE
EIGHT DIFFERENT COMBINATIONS
INCLUDING A NEGATIVE CONTROL.
ON THE LEFT SIDE WE CAN SEE
AMPLIFICATION EACH OF THESE
COMBINATIONS OF RNA, AND IT IS
SUMMARIZED IN A CONFUSION MATRIX
WHERE THE COLORS PRESENT THE
NUMBER OF CORRECT
CLASSIFICATIONS, AND FROM THIS,
WE CAN SEE THAT THE MOST NUMBER
OF MISCLASSIFICATIONS ARE FOR
THE COMBINATION WHICH HAS ALL
THREE RNAs TOGETHER, WHICH
COULD SUGGEST THAT THERE IS
VARIABILITY IN AMPLIFICATION
KINETICS.
AND FOR SIMPLE PURE RNA TEST, WE
COULD DETECT UP TO 80% OF
SAMPLES CORRECTLY.
MOVING ON THE RIGHT SIDE, THEY
WERE SUBJECT TO PORTABLE RNA
EXTRACTION AND THEN COMPARING,
WE COULD SEE 77% AGREEMENT
BETWEEN THE TWO.
SO TO CONCLUDE, WE HAVE
DEVELOPED A SCALABLE AND
ADAPTABLE MACHINE LEARNING MODEL
INTEGRATED INTO A PORTABLE
DEVICE, AND WE CAN SEE 77%
AGREEMENT WITH PCR, AND THE
FUTURE WORK WILL REVOLVE AROUND
LINKING THE INDIVIDUAL -- WITH
BEHAVIOR IN A COMBINATION AND AN
ASSAY TO MATCH WELL WITH PCR.
>.>> THANK YOU.
>> NEXT IS ANIRUDDH SARKAR.
>> MY GOAL HERE IS TO INTRODUCE
MY POSTER AND INVITE YOU TO TALK
MORE OVER THERE.
I'M GOING TO INTRODUCE THIS
WORK, WE DO IN ANTIBODY OMICS.
YOU MIGHT BE THINKING WHAT IS
THIS NEW OMICS, I'M GOING TO
TELL YOU ABOUT IT IN A SECOND
HERE.
SO MY LAB BROADLY DOES MICRO
NANOTYPE SYSTEMS FOR VARIOUS
APPLICATIONS, DISCOVERY,
DIAGNOSIS AND MOST RECENTLY SOME
THERAPEUTIC WORK AS WELL.
HERE I TALK MORE ABOUT OUR
BIOMARKER DISCOVERY WORK, WHERE
WE USE THESE TOOLS TO DO MICRO
SCALING MONITORING IN A VERY
HIGH-THROUGHPUT MANNER FROM VERY
SMALL SAMPLE VOLUMES AND THEN
APPLY MACHINE LEARNING TO
GENERATE THESE MULTIVARIATE
BIOMARKERS BUT MORE RECENTLY
GENERATE HYPOTHESES FROM THIS AS
WELL, WE ALSO TRANSLATE THIS TO
POINT OF CARE DIAGNOSTICS.
OUR FOCUS IS ON THE -- WE WANT
TO LOOK AT ANTIBODIES BUT
REMEMBER TYPICAL ANTIBODY TESTS
JUST LOOK AT YES-NO.
THAT CAN BE USEFUL AT TIMES LIKE
IN HIV BUT IN OTHERS, NOT SO
USEFUL FOR DIAGNOSING
INFECTIONS.
WE WANT TO LOOK BEYOND YES AND
NO, ESPECIALLY THE FCN, WHICH IS
SHOWN TO BE -- WITH
INFLAMMATION.
SO WE THINK THIS IS KIND OF LIKE
A BARCODE -- TELL THE IMMUNE
SYSTEM WHAT TO DO WITH IT.
SO THIS BARCODE IS OFTEN IN
VIVO, CELL FUNCTIONS, BUT IN
DIAGNOSTIC TESTING IS OFTEN
IGNORED SO WE STARTED BY
DEVELOPING METHODS ON HOW TO
READ THIS FUNCTIONAL BARCODE,
AND THESE ARE BEAD-BASED ASSAYS,
CODED WITH ANTIGENS, VARIOUS
PROBES, ISOTYPE-TYPE PROBES, BUT
THE KEY OF THE MODIFICATION ON
ALL HUMAN ANTIBODIES IS A
GLYCOSYLATION.
THIS WAS DIFFICULT TO READ USING
PROBES, SO THAT'S SOMETHING WE
HAD DONE FOR A BIT AND DEVELOPED
THESE METHODS WHICH CAN
REPLICATE MASS SPEC WHICH TAKES
A LOT OF WORK AND A LOT OF
SAMPLE BUT IN A MUCH MORE
CHEAPER WAY AND THOUSAND FOLD
LOWER SAMPLES SO NOW WE CAN
ACTUALLY COME INTO THIS HIGHLY
MULTIPLEXED ANTIBODY FAB AND
XC -- WHICH WE INITIALLY HAD
APPLIED TO COVID BACK IN THE DAY
AND THIS IS PUBLISH WORK SO I'LL
JUST LEAVE YOU WITH THE
CONCLUSION HERE THAT WE SHOWED
FROM A DAY ONE BLOOD DRAW WHEN
THE PATIENT SHOWS UP WE'RE ABLE
TO PREDICT WITH THESE ANTIBODY
OMICS MARKERS THE DISEASE SCORE
SO SURVIVAL VERSUS NON-SURVIVAL,
THIS WAS IN THE PREVACCINE ERA.
MOST RECENTLY WE'VE APPLIED THIS
TO OTHER CONDITIONS WHERE IN
ENDEMIC DISEASES, IN ENDEIN IK
AREAS, EVERYBODY HAS ANTIBODIES.
SO HAVING THE ANTIBODY IS NOT A
CLINICALLY USEFUL METRIC THERE,
BUT WHAT WE'VE SHOWN VIA
ANTIBODY OMICS IS THAT WE CAN
DISTINGUISH CURRENT VERSUS
INFECTION AND EVEN DEFINE UNDOOR
USER TYPES, THIS PAPER JUST CAME
OUT LAST MONTH.
AND THEN SINCE WE'VE BEEN
APPLYING THIS TO OTHER DISEASES,
MOST RECENTLY IN TUBERCULOSIS
WHERE THERE'S A LOT OF
HETEROGENEITY, SO PEOPLE
LATENTLY INFECTED VERSUS CAN
HAVE ACTIVE DISEASE, AND IN
INDEMIC AREAS, A LARGE FRACTION
OF THE POPULATION IS LATENTLY
INFECTED SO EVERYBODY IS
ANTIBODY POSITIVE.
SO THE THEME REMAINS THE SAME
AND WHAT WE SHOWED IS WHILE ABT
BODY -- THEY ACTUALLY PROVIDE
VERY ROBUST BIOMARKERS SO I'M
SHOWING FROM TWO SEPARATE
COHEARTS, WE CAN GET VERY GOOD
DIAGNOSTIC VARIABILITY WITH
THESE MARKERS USING MACHINE
LEARNING-TYPE METHODS.
SO GOING FORWARD WHAT ARE WE
TRYING TO DO?
OF COURSE IN THE TB SPACE, WE'RE
DOING THERAPY MONITORING,
MULTIPLEXING, BUT ALSO YOU KNOW
IT'S NOT JUST FOR DIAGNOSTICS.
WE CAN USE THIS TO LOOK AT
CORRELATES OF PROTECTION AND
LONGEVITY OF PROTECTION AND
VACCINE MODELS GOING AGAINST
INFECTIOUS DISEASES, IN
TRANSPLANTS, AND I SEE THAT I AM
GETTING KICKED OUT, SO I'LL JUST
THANK MY TEAM AND FUNDING
SOURCES AND INVITE YOU TO MY
POSTER TO TALK MORE AND WE HAVE
FOUR SEPARATE TALKS ON THE POINT
OF CARE DIAGNOSTICS ASPECTS OF
MY LAB.
THANK YOU VERY MUCH.
>> THAT IS GREAT.
YES, THESE ARE POSTER
ADVERTISERS, THEY ARE PLUGGING
IT WELL.
OUR NEXT PRESENTER IS DR. KIARA
LEE, PLEASE.
>> HI, EVERYBODY.
MY NAME IS KE KE KIAR, A, THIS S
GOING TO BE DIFFERENT THAN SOME
OF THE RESEARCH WE'VE SEEN
TODAY, MORE ON THE QUALITATIVE
RESEARCH SIDE BECAUSE I'M REALLY
INTERESTED IN HOW WE CAN
INCREASE ACCESS TO TECHNOLOGIES
WORLDWIDE SO AN IMPORTANT ASPECT
OF THAT IS UNDERSTANDING THE
CONTEXT AND DIFFERENT CONTEXTS
THAT WE'RE WORKING IN, SO I
DECIDED TO APPLY TO A POSTDOC
THAT WAS FUNDED THROUGH THE
FOGARTY CENTER, INTERNATIONAL
CENTER, AND ALSO NIDID, SO THANK
YOU FOR THE FUNDING.
AND SO I EXPLORED HOW WE CAN
REALLY HELP INNOVATORS IN PERU
AND EVERYWHERE, IMPROVE THEIR
ACCESS TO TECHNOLOGIES AND HOW
THEY CAN DEVELOP TECHNOLOGIES.
SO LET'S THINK BACK TO COVID-19
AND WE SAW THIS HEADLINE, THERE
ARE A SHORTAGE OF PPE, SHORTAGE
OF A LOT OF THINGS WORLDWIDE AND
WHO SAYS OKAY, EVERYWURNTION
INCREASE YOUR MANUFACTURING
CAPACITY BY 40%.
BUT WHAT IF YOU'RE IN A PLACE
THAT YOU CAN'T DO THAT?
IF YOU'RE NOT USED TO PRODUCING
YOUR OWN TECHNOLOGIES, YOU'RE
USED TO GETTING THEM FROM
SOMEWHERE ELSE, THEY'RE NOT
SHARING THEM BECAUSE WE'RE IN A
PANDEMIC, YOU WANT TO PROTECT
YOUR OWN, SO WHAT THIS SHOWED IS
THAT THERE'S A LOT OF PLACES AND
COUNTRIES THAT DON'T HAVE THAT
ABILITY TO BOOST THEIR OWN
BIOLOGICAL PRODUCT.
MANY DID TRY.
PERU IS AN EXAMPLE OF A COMPANY
THAT DID TRY AND DEVELOPED
TECHNOLOGIES BUT THEY RAN INTO I
A INTO ALOT OF BARRIERS.
WHAT HAPPENS IS YOU DON'T HAVE
ACCESS TO A LOT OF THESE
TECHNOLOGIES AND A LOT OF PEOPLE
END UP DYING UNFORTUNATELY.
SO IN PERU, THEY HAD THE HIGHEST
NUMBER OF DEATHS IN THE WORLD
FROM COVID-19 DESPITE HAVING A
REALLY QUICK RESPONSE.
PART OF THIS WAS DUE TO THE LACK
OF PRODUCTION OF MEDICAL DEVICES
THAT CAME FROM WITHIN THE
COUNTRY.
SO THAT IS KIND OF WHAT
MOTIVATED THE RESEARCH QUESTION
OF WHAT ARE THESE BARRIERS AND
FACILITATORS IN MAKING MEDICAL
DEVICES IN PERU.
AND SO WE WROTE THIS DOWN TO
THREE MAIN QUESTIONS, ONE, HOW
DO WE EXPLAIN WHAT'S GOING ON IN
PERU, WHAT'S THE PIPELINE THERE,
THEN WHAT ARE THE ACTUAL
BARRIERS AND FACILITATORS, AND
LASTLY MAKING RECOMMENDATIONS
FOR THE COUNTRY AND ALSO
EVERYBODY ELSE AND HOW WE CAN
HELP COLLABORATE ON THISSISH YO.
SO WE ALL KIND OF KNOW THIS
PIPELINE OF HOW WE GO FROM
RESEARCH TO CLINICAL TRIALS, TO
REGULATORY APPROVAL,
MANUFACTURING, EVENTUALLY THINGS
ARE BEING UTILIZED, SO THIS IS
WHERE WE SOURCED PEOPLE FOR THE
INTERVIEWS FOR THIS PROJECT.
AND SO WE INNED UP INTERVIEWING
31 PARTICIPANTS.
IF YOU'RE NOT FAMILIAR WITH THIS
TYPE OF RESEARCH, THAT'S ENOUGH.
PEOPLE START TO REPEAT
THEMSELVES AFTER A WHILE, SO
THAT'S GOOD ENOUGH.
AND SO WE DID GO FROM
RESEARCHERS, WE TALKED TO
REGULATORY PEOPLE, PEOPLE THAT
WORK AT KIND OF INCUBATOR-TYPE
THINGS, ACADEMICS THAT TRIED TO
COMMERCIAL SIZE SOMETHING,
PRIVATE COMPANIES, BIG
COMPANIES, ET CETERA SO WHAT WE
FOUND BASICALLY WAS THAT IN THIS
CONTEXT, PEOPLE GET FUNDING FROM
THE GOVERNMENT, INTERNATIONAL
COLLABORATIONS AND THEN THEY GO
THROUGH THIS PROCESS STARTING
WITH MOBILE APPLICATION, YOU
KIND OF FOLLOW THAT TYPICAL
PATHWAY STARTUP, GETTING
INVESTORS, SMALL COMPANIES, ET
CETERA, BUT WHAT IS THE BIG
DIFFERENCE WITH MEDICAL DEVICES?
ENTERING INTO THIS REGULATORY
SYSTEM.
BUT WHAT WE SAW WAS THAT PEOPLE
WERE ENTERING NO I ENTERING INTD
NOT COME OUT.
MEDICAL DEVICES ARE WAY MORE
EXPENSIVE TO PRODUCE THAN AN
APP.
WE ALSO LOOKED AT THE
PHARMACEUTICAL INDUSTRY AS WELL.
WHAT WE SAW MULTI-NATIONAL
COMPANIES LIKE YOUR J & Js, ET
CETERA, THEY DO R & D SOMEWHERE
ELSE, THAT MEANS THAT THEY'RE
NOT CULTIVATING THE R & D WITHIN
THE COUNTRY, AND THERE ARE SOME
SMALL COMPANIES IN PERU THAT DO
MANUFACTURE BUT MORE SO ON THE
GENERIC, NOT NEW AND INNOVATIVE
PRODUCTS.
AND SO THESE ARE JUST SOME OF
THE BARRIERS AND FACILITATORS.
YOU CAN COME TALK TO ME A LITTLE
BIT MORE AT THE POSTER ABOUT
THEM, BUT BASICALLY IN TERMS OF
BARRIERS, THERE'S LIMITED CLAB
RAIGS WITHIN PERU.
THEY KIND OF GO OUTSIDE THE
COUNTRY.
BUT THERE'S A LOT OF
OPPORTUNITIES FOR
COLLABORATIONS, KIND OF LIKE THE
PANEL WAS TALKING ABOUT.
AND ALSO THE CURRENT REGULATIONS
DON'T SUPPORT THAT MEDICAL
DEVICE INNOVATION, AND THEN THE
MARKET SIDE, YOU HAVE A
DIFFERENT HEALTHCARE STRUCTURE
WHERE THE GOVERNMENT FUNDS A LOT
OF HEALTHCARE SO THEN YOU HAVE
TO SELL YOUR PRODUCT TO THE
GOVERNMENT WHICH IS KIND OF
DIFFICULT.
BUT IN TERMS OF WHAT THEY'RE
DOING WELL, THEY HAVE A VERY,
VERY ACTIVE BIOMEDICAL
INNOVATION SECTOR, AND I IT'S
GROWING.
WHAT WOULD HELP IS INCENTIVES.
SO INCENTIVIZING PEOPLE TO WANT
TO DEVELOP MEDICAL DEVICES,
MAKING SURE THEY HAVE ENOUGH
FUNDING TO DO THAT, AND LASTLY
AT FACILITATOR WAS ANOTHER
ISSUE, LIKE OH, IT MUST COME
FROM THIS COUNTRY FOR US TO
TRUST IT, BUT THAT IS NOT
SOMETHING THAT WE SAW.
SO I JUST WANTED TO END WITH
SAYING THAT THIS WORK WAS
IMPORTANT FOR PERU BUT ALSO FOR
US HERE, HOW WE CAN REALLY
CULTIVATE COLLABORATIONS AND
EXPAND OUR -- EXPAND THE
OPPORTUNITIES FOR DEVELOPING NEW
HEALTH TECHNOLOGIES EVERYWHERE.
I JUST WANTED TO THANK EVERYONE
THAT HELPED ME OUT WITH THIS
STUDY, MY RESEARCH ASSISTANTS,
MENTORS, AND THANK YOU ALL FOR
LISTENING.
[APPLAUSE]
>> THAT WAS GREAT.
DR. RUBIN BASS RUBIN BASKIR, GO.
>> I'M RUBIN BASKIR, THE
RESEARCHER ENGAGEMENT OUTREACH
BRANCH DIRECTOR AT THE ALL-OF-US
RESCH PROGRAM.
I'M PRESENTING A CODEVELOPED
TRAINING PROGRAM TO INCREASE
UNDERREPRESENTED RESEARCHERS IN
THE BIOMEDICAL WORKFORCE AND BY
THE END OF THIS PRESENTATION,
I'LL REVEAL WHAT IS UNDER THIS
HALLOWEEN SHEET, SO YOU'LL HAVE
TO STAY TO THE END FOR THAT.
AND YOU'LL ALSO LEARN WHY YOU
SHOULD VISIT POSTER 44.
SO ARTIFICIAL INTELLIGENCE
MACHINE LEARN SOMETHING A
RAPIDLY ADVANCING FIELD WITH
INCREASING PUBLIC AWARENESS.
ITS APPLICATION TO PRECISION
MEDICINE IS A CLEAR POTENTIAL
BENEFIT AND ONE THAT ALSO HAS A
RISK TO EXACERBATE HEALTH
DISPARITIES, IF NOT VIEWED
THROUGH THE LENS OF HEALTH
EQUITY.
SO TO INCREASE THE NUMBER OF
RESEARCHERS UNDERREPRESENTED IN
THE BIOMEDICAL WORKFORCE IN THIS
SPACE, THE ALL-OF-US RESEARCH
PROGRAM, RTI INTERNATIONAL AND
THE ARTIFICIAL INTEL JEPS
MACHINE LEARNING AND DIVERSITY
OR AIM AHEAD DEVELOPED AN
8-MONTH TRAINING PROGRAM WHOSE
IP AUGUST RAL COHORT COMPLETED
THIS PAST AUGUST.
SO TO GO OVER SOME OF THE
PARTNERS, THIS IS A LONGITUDINAL
RESEARCH PROGRAM LOOKING TO
ENROLL A MILLION OR MORE PEOPLE
FOR 10 YEARS OR MORE.
WITH THE AIM OF ACCELERATING
HEALTH RESEARCH AND PRECISION
MEDICINE.
SO THE PROGRAM'S COHORT IS BOTH
LARGE AND DIVERSE, BOTH IN TERMS
OF DATA SITES AVAILABLE AND THE
BACKGROUNDS OF PARTICIPANTS
INCLUDED.
OVER 570,000 PARTICIPANTS HAVE
COMPLETED THE INITIAL STEPS FOR
ENROLLMENT AN OVER 87% OF
PARTICIPANTS ARE
UNDERREPRESENTED IN BIOMEDICAL
RESEARCH AND OVER 45% ARE
UNDERREPRESENTED BY RACE OR
ETHNICITY.
SINCE MAKING THE DATA AVAILABLE
TO RESEARCHERS IN 2020, MORE
THAN 13,000 RESEARCHERS HAVE
REGISTERED TO ACCESS THE DATASET
AND MORE THAN 430 PUBLICATIONS
ON THE DATASET ARE AVAILABLE IN
PEER REVIEWED JOURNALS.
SO BECAUSE OF A MUTUAL FOCUS ON
HEALTH EQUITY, ALL-OF-US
COLLABORATE WITH AIM AHEAD TO
SUPPORT UNDERREPRESENTED
RESEARCHERS AND THE BIOMEDICAL
WORKFORCE APPLYING AIML
APPROACHES TO THE ALL-OF-US
DATASET.
SO IF YOU'D LIKE TO CONNECT WITH
OUR OSTLES AT THE ALL-OF-US
RESEARCH PROGRAM TO LEARN MORE,
A QR CODE IS AVAILABLE THERE.
AND IF YOU'D LIKE TO KNOW MORE
ABOUT OUR WORK THROUGH AN ANNUAL
REPORT, THAT'S ALSO AVAILABLE BY
THE QR CODE ON THIS SLIDE.
SO NOW EYE G I'LL GIVE YOU AN OW
OF OUR PARTNER AIM AHEAD.
THE NIH RECOGNIZED THERE WAS A
NEED FOR UNDERREPRESENTED
INSTITUTIONS AND COMMUNITIES TO
BE INCLUDED IN AIML RESEARCH AND
HEALTH EQUITY AND THREE YEARS
AGO, AIM AHEAD WAS DEVELOPED TO
INCREASE PARTICIPATION AND
REPRESENTATION OF RESEARCHERS
AND COMMUNITIES THAT ARE
UNDERREPRESENTED IN THIS SPACE.
SINCE THEN, AIM AHEAD HAS
CREATED A NATIONWIDE CONSORTIUM
INVOLVING 29 LEAD INVESTIGATORS,
AND 50 RESEARCHERS, AN AND A
NETWORK OF CLOSE TO 5,000
MENTORS, RESEARCHERS AND
TRAINEES.
NOW, WE HAVE LEADERSHIP PUBS AND
FUNCTIONAL CORES THAT WORK
TOGETHER TO BUILD RELATIONSHIPS
WITH DIVERSE RESEARCHERS AND THE
PROGRAM REALLY FOCUSES ON
DEVELOPING AND IMPLEMENTING DATA
SCIENCE AND TRAINING CONSORTIUM,
PROVIDES OPPORTUNITIES FOR
INVESTIGATORS TO ADDRESS HEALTH
DISPARITIES BY LEVERAGING AI AND
DIVERSE HEALTH DATASETS, AND
BUILDS CAPACITY BY IMPROVING
CAPABILITIES AND TECHNOLOGIES OF
UNDERREPRESENTED COMMUNITIES.
SO AIM AHEAD WORKING WITH
ALL-OF-US DEVELOPED AN
EIGHT-MONTH TRAINING PROGRAM FOR
23 TRAINEES.
THE PROGRAM IS SPLIT INTO FOUR
PARTS.
THE FIRST ARE SHORT COURSES
REALLY DESIGNED TO BRING PEOPLE
UP TO SPEED ON DATA SCIENCE
TRAINING AND PROGRAMMING.
THE SECOND PROVIDES USE CASES TO
DEMONSTRATE HOW ALL-OF-US CAN BE
USED IN RESEARCH.
THE THIRD IS ACTUALLY THE
DEVELOPMENT OF RESEARCH
QUESTIONS SO THAT TRAINEES CAN
ACTUALLY EXPLORE RESEARCH THAT'S
INTERESTING TO THEMSELVES.
AND THE FINAL PART IS A POSTER
PRESENTATION AT AN ANNUAL
RESEARCH SYMPOSIUM.
SO THE PROGRAM WAS EVALUATED
WITH A MIDPOINT AND END POINT
SURVEY THAT CONTAINED BOTHLY
KERT SCALE-TYPE QUESTIONS AND
OPEN-ENDED RESPONSES.
BOTH SURVEYS HAVE ACTUALLY BEEN
COMPLETED BUT ONLY THE MIDPOINT
SURVEY HAS BEEN ANALYZED RIGHT
NOW.
AND OUR PRELIMINARY FINDINGS
FROM THE MIDPOINT SURVEY
INDICATE THAT THE PROGRAM'S
MULTICOMPONENT STRUCTURE, THE
SHORT COURSES, MENTORSHIP AND
COACHING SUPPORT FOR CODING AND
ANALYSIS, THAT COLLABORATIVE
APPROACH WITH MULTIPLE PARTNERS
IS REALLY EFFECTIVE FOR AIML
TRAINING.
SO KEY QUESTIONS INDICATE THAT
FROM THE MIDPOINT SURVEY
INDICATE THAT 80% OF TRAINEES
FEEL EQUIPPED TO CONDUCT
ANALYSIS WP T WITHIN THE ALL-OFS
RESEARCH PROGRAM, THEY FELT
SATISFIED WITH THE TYPE OF
SUPPORT THEY RECEIVED FROM THE
PROGRAM AND THEY ALSO COULD
IDENTIFY ETHICAL CONCERNS IN THE
USE OF AIML.
SO NOW FOR THE MOMENT YOU'VE ALL
BEEN WAITING FOR, WHAT IS UNDER
THIS HALLOWEEN SHEET?
IT IS, IN FACT, OREOS THAT ARE
HALLOWEEN FLAVORED, THESE WERE
BOUGHT WITH PRIVATE FUNDS, NOT
GOVERNMENT FUNDS, SO IF YOU'RE
INTERESTED IN LEARNING MORE
ABOUT OUR PROGRAM OR GETTING A
FEW OREOS, I'D ALSO LIKE TO LET
YOU KNOW, WE ARE HOSTING A
SECOND INAUGURAL TRAINING
PROGRAM ON OCTOBER 31ST, THAT'S
NOT A JOKE, IT'S ACTUALLY HOSTED
OP HALLOWEEN.
IF YOU'D LIKE TO LEARN MORE, YOU
CAN FOLLOW THIS QR CODE, AND SO
IF YOU'RE INTERESTED, YOU CAN
LEARN MORE AT POSTER 44.
THANK YOU.
[APPLAUSE]
>> HE'S GOING TO RUN OUT OF
THOSE OREOS SO GET TO THAT
POSTER QUICKLY.
SORRY, I LOVE THAT.
OKAY.
AND NOW, OUR FINAL RAPID FIRE,
I'M SUPER PLEASED TO PRESENT,
THIS IS DR. PAM ROBEY.
DR. ROBEY, PLEASE.
NATIONAL INSTITUTE OF DENTAL AND
CRANIOFACIAL RESEARCH.
>> SO THANK YOU VERY MUCH FOR
THE OPPORTUNITY TO TALK ABOUT
OUR EFFORTS TO USE STEM CELLS IN
A BIOMATERIAL TO GENERATE STABLE
FUNCTIONAL CARTILAGE.
AS MOST OF YOU KNOW,
OSTEOARTHRITIS IS A MAJOR GLOBAL
PROBLEM, AND WHILE THERE ARE A
NUMBER OF CURRENT TREATMENTS,
MOST ARE PRIMARILY PALLIATIVE.
SO THERE IS A GREAT DEAL OF
EFFORT IN PARTICULAR BY USING
HUMAN BONE MARROW, STROMAL CELLS
AND CHONDROCYTE-LIKE CELLS
DERIVED FROM IPS CELLS TO
DIFFERENTIATE AND REGENERATE
FUNCTIONAL CARTILAGE.
HOWEVER, IN VITRO, HUMAN BONE
MARROW STROMAL CELL ORGANOIDS
INITIALLY FORM CARTILAGE BUT IF
YOU TRANSPLANT THEM INTO A
MOUSE, THEY UNDERGO HYPERTROPHY
INTO BONE AND AS YOU MIGHT
IMAGINE, THIS IS NOT
PARTICULARLY GOOD FOR AN
OSTEOARTHRITIC JOINT.
HOWEVER, WHEN WE TAKE BMSCs
AND WE ATTACH THEM TO MY BRIN
MICRO BEADS THAT ARE COATED WITH
ACID AND PUT THEM INTO THE
SUBCUTANEOUS TRANSPLANT, WE WERE
SURPRISED TO SEE THAT THEY
FORMED VERY STABLE CARTILAGE
THAT REMAINED THERE FOR OUT TO
SEVEN MONTHS.
BECAUSE THE SIGNALING PATHWAYS
THAT DIRECT FORMATION OF STABLE
CARTILAGE ARE NOT WELL-KNOWN,
BMSC CONSTRUCTS WITH AND WITHOUT
THE BEADS WERE PREPARED AND THEN
WE FOLLOWED THEIR TRANSCRIPTOMIC
PROFILE AS A FUNCTION OF TIME
AND CULTURE.
AND WHAT WE FOUND WHILE DOING
THIS, IN THE EARLY CULTURES, WE
FOUND INCREASING PRECARTILAGE
PROTEIN SUCH AS MATRIX --
PROTEIN AND IGFBP5 AND WE SAW A
REDUCTION IN BMP SIGNALING, AT
LATER TIMES IN CULL TEU CULTUREE
SOUGHT EX-PREX OF MARKERS SUCH
AS SOX 9, BUT WE SAW A
RE-ESTABLISHMENT OF BONE
MORPHOGENETIC SIGNALING.
HOWEVER, UNLIKE WHEN WE PUT THE
BMSC CONSTRUCTS UNDERNEATH THE
SKIN, WE PUT THOSE CONSTRUCTS
INTO AN INJURED CARTILAGE, THEY
STARTED TO DEGENERATE AND
EXPRESS TYPE 10 COLLAGEN, WHICH
IS A MARKER OF HYPERTROPHY.
MEANING THAT WE NEED TO
MANIPULATE THESE BMSCs MUCH
MORE BEFORE WE CAN USE THEM IN
CARTILAGE REGENERATION.
WE THEN DEVELOPED AN ALTERNATE
SOURCE OF CHONDROGENIC CELLS BY
GUIDING HUMAN IPS CELLS THROUGH
A DEVELOPMENTAL PROCESS USING
THE NEW INFORMATION THAT WE GOT
FROM THE BMSC COU CONSTRUCTS.
WHAT WE DID WAS WE EMPLOYED THE
INHIBITION OF BMP SIGNALING.
INITIALLY.
THEN WE BROUGHT IT BACK, AND
THIS LED TO THE GENERATION OF
WHAT WE CALL CHONDRO SPHEROIDS.
SO WE CHARACTERIZED THESE
CHONDROSPHEROIDS AND FOUND THEY
HAD HIGH LEVELS OF STAINING WITH
TAU BLUE STAINED SPECIFIC FOR
CARTILAGE MATRIX AND THEY HAD
HIGH EXPRESSION OF TYPE
2 CARTILAGE COLLAGEN WITH A LACK
OF EXPRESSION OF TYPE I AND TYPE
10 WHICH ARE INDICATIVE OF
HYPERTROPHIC CARTILAGE AND THEY
ALSO HAD HIGH LEVELS OF THE
PROTEOGLYCAN AGGRECAN AND
LUPROCEN.
WHEN WE TOOK THESE
CHONDROSPHEROIDS AND DID
TRANSCRIPTOMIC ANALYSIS, WE SAW
THAT THERE WAS A SEQUENTIAL
EXPRESSION OF CHONDROGENIC GENES
AND AS THEY MATURED IN CULTURE,
WE SAW THE EMERGENCE OF A
CHONDROGENIC PATTERN WITH GENES
THAT ARE VERY NEAR AND DEAR TO
OUR HEARTS IN THE CARTILAGE
FIELD.
AND WHEN WE UNDERWENT ANALYSIS
IN PCA, WE SAW THAT THEY WERE
VERY SIMILAR TO NATIVE CARTILAGE
FOUND IN EMBRYONIC FETAL ADULT
AND ADOLESCENT CARTILAGE.
NEXT WE TOOK THESE
CHONDROSPHEROIDS AND PUT THEM
INTO THE INJURED ARTICULAR
CARTILAGE, BUT LIKE THE BMSCs,
THEY UNDERWENT DEGRADATION.
BUT WHEN WE DIGESTED THE CELLS
AND PUT THEM BACK ON TO THE
FIBROMICRO BEADS, WE FOUND THAT
THEY MADE VERY, VERY GOOD
CARTILAGE OUT TO FIVE MONTHS,
INDICATING THAT THE MICRO BEADS
ARE ESSENTIAL FOR THIS PROCESS.
THEY ALSO MADE THE CARTILAGE OF
HUMAN ORIGIN WITH ALL OF THE
PROTEINS THAT WE FIND IN NORMAL
CARTILAGE, BUT THERE WAS NO SIGN
OF HYPERTROPHY.
SO I WOULD LIKE TO ACKNOWLEDGE
THE ARMY, S TEPMEN GADOMSKI
ALONG WITH THE OTHER MEMBERS OF
MMY SECTION, AND I'D BE HAPPY TO
ANSWER QUESTIONS AT POSTER 63.
>> THANK YOU VERY MUCH.
WONDERFUL.
GREAT.
[APPLAUSE]
SO THANK YOU ALL FOR THOSE RAPID
FIRE PRESENTATION.
NOW WE WILL FREE YOU ALL TO GO
AND LOOK THE A THEIR POSTERS
THAT SHOULD BE POSTED UP IN THE
FAES STAIRS AND JUST WANT TO
REMIND YOU ALL, PLEASE BE BACK
IN THIS ROOM READY FOR OUR
AFTERNOON KEYNOTE, THE WONDERFUL
THE AT 3:00.THANKS A LOT.
WELCOME BACK.
I HOPE YOU ALL ENJOYED THE
BREAKOUT SESSIONS AND THE POSTER
SESSION.
SO THAT WAY WE CAN EXPOSE YOU TO
A LOT MORE OF THE WORK HAPPENING
HERE AT NIH AND ACROSS THE
COUNTRY AND INTERNATIONAL LABS
AS WELL.
AGAIN MY NAME IS DR. MANU PLATT,
PLEASED TO INVITE YOU BACK FOR
OUR AFTERNOON KEYNOTE FROM AN
EXTRAMURAL RESEARCHER AND WE ARE
SUPER EXCITED TO HAVE AS OUR
PLENARY SPEAKER DR. RASHID
BASHIR WHO IS THE DEAN OF THE
GRANGER COLLEGE OF ENGINEERING.
YOU CAN READ HIS WONDERFUL BIOIN
THE INTRO BUT HE IS A RECENT EE
LEK TEE TO THE NATIONAL ACADEMY
OF MEDICINE AND EVER SINCE I'VE
KNOWN HIM HE HAS BEEN DOING
CUTTING EDGE WORK, MAKE
ENGINEERING THINGS, CELLS DO
WHAT WE ASK OF THEM TO DO IN
NON-NATIVE, NON-INSTRUCTIVE WAYS
BUT HOW YOU CAN DRIVE THAT AND
ALSO DOES ON THE DIAGNOSTIC
TECHNOLOGY SIDE REALLY PAYS
ATTENTION TO GLOBAL HEALTH,
MAKING LOW COST ACCESSIBLE
TECHNOLOGIES.
THEN ALSO HE WILL TALK ABOUT
THIS I THINK BUT HIS OTHER BIG
CLAIM TO FAME THAT I'M SUPER
PROUD TO HAVE HIM TALK ABOUT IS
THAT HE WAS ONE OF THE PEOPLE
WHO REALLY HELPED ENVISION WITH
THE TEAM THE IDEA OF AN
ENGINEERING MEDICAL SCHOOL AND
HAS PUT THAT AS THE FIRST ONE.
SO HERE WE ARE, DR. RASHID
BASHIR.
[APPLAUSE]
>> GOOD AFTERNOON.
GOOD AFTERNOON?
>> GOOD AFTERNOON.
>> I KNOW IT'S LATE IN THE
AFTERNOON, SO WE'VE HAD ENOUGH
COFFEE TO KEEP IT GOING.
THANK YOU, MANU, FOR ORGANIZING
THIS SYMPOSIUM.
WHEN MANU ASKS I CAN'T SAY NO,
SO THIS HAS BEEN A GREAT
OPPORTUNITY TO CONNECT AND TALK
TO OTHER COLLEAGUES AT NIH AND
OTHER PARTNERS.
SO I WILL TALK ABOUT -- I KNOW
I'M PREACHING TO THE CHOIR WHEN
I SHOW THIS SLIDE, AND BEFORE I
SHOW THIS SLIDE I DO WANT TO
RECOGNIZE BRUCE IS NOT HERE, BUT
I THINK NIH AND NIBIB HAVE BEEN
SO INSTRUMENTAL TO MY CAREER AND
SO MANY CAREERS IT'S CHANGED
LIVES AND LTS, I THINK DURING
COVID, ESPECIALLY BRUCE DID A
PHENOMENAL JOB WITH THE ENTIRE
COVID RESPONSE AND THE
DIAGNOSTIC DEVICES AND RADX
PROGRAM SO I DID WANT TO
ACKNOWLEDGE THAT.
I KNOW HE'S NOT HERE BUT I STILL
WANTED TO SAY THAT.
AND BRUCE ALSO GOT ELECTED INTO
THE NATIONAL ACADEMY OF
ENGINEERING THIS PAST YEAR, AND
THAT INDUCTION CEREMONY WAS JUST
A FEW WEEKS AGO, SO WE SHOULD
GIVE BRUCE A ROUND OF APPLAUSE
EVEN THOUGH HE'S NOT HEREMENT
[APPLAUSE] HERE.
[APPLAUSE]
SO I HAD THE PLEASURE ACTUALLY
THROUGH A CENTER THAT WE HAD
WITH GEORGIA TECH, MIT AND
ILLINOIS, I HAD THE GREAT
PLEASURE TO CONNECT WITH BOB
NAREM, A MENTOR TO MANY HERE, TO
MANU BUT CERTAINLY TO ME AS WELL
AND A FEW OTHER LUMINARIES SO I
DON'T KNOW HOW I SHOWED UP IN
THAT FORE, BUT ENGINEERING AS A
NEW FRONTIER FOR TRANSLATIONAL
MEDICINE, SO YOU THINK LIKE I
SAID I'M PREACHING TO THE CHOIR,
BUT THE GOAL IS THAT THIS
ENGINEERING VERSUS MEDICINE, IT
SHOULDN'T BE THE CASE.
THESE TWO FIELDS NEED TO MERGE
AND I DO THINK SOME DAY BIOLOGY
AND MEDICINE WILL BE ENGINEERING
AND IT'S NOT BECAUSE WE ARE
ENGINEERS BUT RATHER ENGINEERING
IS REALLY ALL ABOUT TAKING LAWS
OF PHYSICS AND CHEMISTRY, USING
THE LANGUAGE OF MATHEMATICS TO
BE ABLE TO FORWARD DESIGN.
THAT'S WHAT ENGINEERING IS.
YOU LEARN THE RULES TO FORWARD
DESIGN AND THE BASIC SCIENCES OR
PHYSICAL SCIENCES IS PHYSICS AND
CHEMISTRY TODAY, I THINK SOME
DAY BIOLOGY WILL BE IN IT TOO, I
THINK BIOLOGY SHOULD BE REQUIRED
OF EVERY ENGINEERING
UNDERGRADUATE, AND SOME DAY I
THINK AS WE LEARN THE DESIGN
RULES, THIS WILL ALL BE THE
SAME.
THE NAME, ENGINEERING AND
MEDICINE IS JUST A NAME.
SO I THINK WE HAVE TO KEEP
WORKING AT IT AND AS WE LEARN
THE DESIGN RULES, WE TRY TO, OF
COURSE, ADVANCE THE FIELD TO
IMPROVE THE HUMAN CONDITION.
SO TODAY I'LL TALK ABOUT REALLY
MY OWN RESEARCH ACTUALLY, BUT
JUST ONE OTHER THING, I LOVE THE
TITLE OF THIS WORKSHOP.
BUILDING BRIDGES ACROSS NIH AND
THE BROADER ENGINEERING
COMMUNITY, I WANTED TO MAKE THAT
COMMENT AS WELL.
AND THERE'S SO MANY
OPPORTUNITIES HERE, YOU KNOW,
ONE THING I USUALLY SAY IS THAT
AS ENGINEERS, WE HAVE ACCESS TO
EVERY DOMAIN, EXCEPT WE DON'T
HAVE AS FREE OF AN ACCESS TO
MEDICINE.
AND IT'S FOR GOOD REASON.
IT'S FOR VERY GOOD REASON.
BECAUSE LIVES ARE AT STAKE.
RIGHT?
BUT THE REALITY IS THAT I CAN GO
BUILD A BRIDGE, DECONSTRUCT A
BRIDGE, I CAN BUILD A CIRCUIT,
DECONSTRUCT A CIRCUIT, OR
BUILDING OR WHATEVER, BUT
MEDICINE IS ONE DOMAIN WHERE WE
DON'T HAVE AS EASY ACCESS.
AND I THINK IF THERE WAS A WAY
TO CREATE THAT, IT WOULD JUST BE
GOOD FOR EVERYONE.
AND EVERY FIELD OF ENGINEERING
NOW, AT LEAST IN OUR COLLEGE AND
I KNOW IN MANY OTHER PLACES,
EVERY FIELD OF ENGINEERING HAS
FACULTY NOW WORKING IN THE
BIOMEDICAL SPACE, INCLUDING
CIVIL ENGINEERING.
WE HAVE CIVIL ENGINEERS THAT
WORK IN STRUCTURE, INCLUDING
BIOLOGICAL STRUCTURES, FOR
EXAMPLE, INDUSTRIAL ENGINEERS
HAVE SO MUCH TO OFFER AND SO
MUCH TO DO WITH OPTIMIZATION AND
HOSPITAL WORKFLOW, AND
ELIMINATION OF MISTAKES SO THERE
ARE MANY OPPORTUNITIES TO BUILD
BRIDGES.
SO TODAY I WAS GOING TO TALK
ABOUT RESEARCH THAT WE'VE BEEN
INVOLVED IN, AND I'M VERY
INTERESTED IN USING MICRO,
NANOAND MACRO SCALE TECHNOLOGIES
AS WELL TO DEVELOP DIFFERENT
TECHNOLOGIES, TO BUILD THINGS AT
THE SMALL SCALE AND THEN APPLY
THEM TO IMPORTANT PROBLEMS SO WE
ARE VERY INTERESTED IN TOOLS AND
PRECISION, PERSONALIZED MET
MEDALLION SIN, LOOKING THE A
SEPSIS AND GLOBAL HEALTH, I'LL
TALK ABOUT SEPSIS TODAY.
WE'RE ALSO VERY INTERESTED IN
USING THESE TECHNOLOGIES
ESPECIALLY THAT ARE MORE
BIO-RELATED, BIOSTEREOLY THOUGH
BIOSTEREOLITHOGRAPHY,
MICROFLUIDICS FOR ALSO SORT OF
THIS NEW EMERGING ENGINEERING
AREA OF BIOROBOTICS AND I'LL
TALK ABOUT THAT.
SO THE KEY TOPICS I WANT TO HIT
TODAY IS PATHOGEN DETECTION FROM
BLOOD, SOME ADVANCED SENSORS FOR
BIOMOLECULES AND APPLICATION TO
SEPSIS, TISSUE FABRICATION, AND
ALSO BIOENGINEERING OF MEDICAL
EDUCATION.
SO LET ME START TALKING ABOUT
SEPSIS.
SEPSIS AND CRITICAL CARE IN
HOSPITAL IS A HUGE PROBLEM.
IT IS REALLY NOT AS WELL
RECOGNIZED.
IT'S THE LEADING CAUSE OF DEATH
IN HOSPITALS IN THE U.S. AND THE
WORLD.
YOU CAN LOOK UP ALL THE
STATISTICS.
1 IN 3 PATIENTS WHO DIE IN A
HOSPITAL HAVE ACTUALLY SEPSIS.
THEIR IMMUNE SYSTEM IS
COMPROMISED OR THEY GET SOME
INFECTION AND THAT RESULTS IN
THIS VERY COMPLICATED SET OF
EVENTS AND CASCADE WHICH IS
SEPSIS, AND WHILE ALL THESE
OTHER DISEASES ARE VERY
IMPORTANT, THERE'S ACTUALLY MORE
CASES OF SEPSIS PER UNIT
POPULATION IN THE U.S. AND
EUROPE THAN MANY OTHER DISEASES.
SO THIS IS SOMETHING THAT'S
IMPORTANT TO SOLVE AND ADDRESS
AND OF COURSE WE ALSO LEARN THIS
THROUGH COVID, THERE'S SOME, OF
COURSE, OVERLAP HERE, BUT THIS
IS WHAT HAPPENS TODAY AT THE
ONSET OF AN INFECTION.
THE PATIENT MIGHT FEEL ABNORMAL,
THEY TAKE SOME TIME HERE TO GET
TO THE HOSPITAL, TO THE
EMERGENCY ROOM, AND THERE'S A
LOT TO BE DONE AT THE
PRE-HOSPITAL AND POINT OF CARE
SENSORS AND POINT OF CARE
DEVICES HAVE A LOT TO DO THERE,
AND THEN WHAT MOST OFTEN HAPPENS
IS THAT A BLOOD CULTURE IS
PERFORMED, BLOOD IS DRAWN, AND A
BLOOD CULTURE IS PERFORMED WHICH
CAN TAKE UP TO FIVE DAYS.
IT HAS TO BE UP TO FIVE DAYS FOR
A COU CONFIRMED NEGATIVE SO THAT
REALLY IS A RATE-LIMITING STEP
IN EVERYTHING THAT HAPPENS.
BLOOD CULTURES COME OUT,
IDENTIFICATION, THERE IS
ANTIBODY SUSCEPTIBILITY TESTING
DONE IN MANY LABS BUT NOT ALL
LABS IN HOSPITALS AND THEN
WHATEVER THE FLOW MIGHT BE FOR
THE PATIENT.
SO BLOOD CULTURE TAKES TOO LONG,
AND AFTER HUNDREDS OF YEARS, WE
STILL HAVEN'T BEEN ABLE TO
BYPASS THAT STEP.
SO THAT'S A GRAND CHALLENGE FOR
ALL OF US.
ANYONE WHO CAN ADDRESS THAT
CHALLENGE AND WITHIN EVEN LET'S
SAY TW 20 TO 30 MINUTES BE ABLEO
DETECT PATHOGENS IN BLOOD, AND
I'LL TALK ABOUT THAT, THAT'S A
HUGE CHALLENGE.
ALSO HOW TO PRIORITIZE AND
STRATIFY PATIENTS AND THE
ANTIBIOTIC TREEMMENTS.
TREATMENTS.
WE ALL KNOW BY NOW ANTIMICROBIAL
STEWARDSHIP AND ANTIBIOTIC
RESISTANCE ARE BIG CHALLENGES
AND AS WE ALL KNOW, WE'RE GIVING
TOO MANY ANTIBIOTICS BECAUSE YOU
DON'T KNOW WHETHER THE PATHOGEN
IS A VIRAL OR A BACTERIAL, THAT
RESULTS DON'T COME FAST ENOUGH.
AND ALSO HOW TO QUANTITATIVELY
PROFILE THE SPECIFIC PATIENT,
THAT PERSON'S IMMUNE SYSTEM OVER
TIME.
THERE'S BEEN SOME GREAT TALKS
TODAY ABOUT THAT AS WELL, ABOUT
TRYING TO DO THAT.
SO LET'S TALK ABOUT THIS BLOOD
CULTURE BUSINESS.
SO THERE'S MORE THAN 30 MILLION
BLOOD CULTURES PER DAY JUST IN
THE U.S.
WHAT HAPPENS IS IN A 5ML OF
WHOLE BLOOD IS DRAWN PER VIAL,
AND ACTUARIACTUALLY TECHNICALLYT
PLACES THERE COULD BE THREE OF
THOSE OR CERTAINLY MORE THAN
ONE, BUT I JUST KIND OF
MENTIONED ALREADY WHAT HAPPENS
BUT THIS IS SOME MORE DETAILS
HERE.
SO WE'RE TRYING TO REDUCE THIS
PROCESS, THE TIME OF THIS
PROCESS.
YOU HAVE TO WORRY ABOUT AEROBIC
OR ANAEROBIC CULTURES, YOU HAVE
TO WORRY ABOUT GRAM POSITIVE AND
GRAM-NEGATIVE.
SO EVEN IF YOU COULD TELL THE
PHYSICIAN IN A VERY SHORT AMOUNT
OF TIME, OF COURSE ALMOST
IMMEDIATELY IS THE GOAL, BUT
CERTAINLY EVEN WITHIN 10 TO 15
TO 20 MINUTES, IF YOU COULD
INFORM WHETHER THE BACTERIA THAT
ARE THERE ARE GRAM POSITIVE,
THEN THERE'S A SET OF
ANTIBIOTICS THAT COULD BE
PRESCRIBED VERSUS GRAM-NEGATIVE
TH,THEN A DIFFERENT SET OF
ANTIBIOTICS WOULD BE PRESCRIBED.
AND THERE IS NO WAY DO THAT
TODAY, REALLY -- I MEAN,
RAPIDLY.
SO JUST LONG STORY SHORT, WE'VE
BEEN THINKING ABOUT THIS FOR A
LONG TIME, FOR A FOOD PATHOGEN
PERSPECTIVE, FROM A FOOD SAMPLE,
YOU HAVE THE SAME PROBLEM.
FROM WATER, FROM ALL SORTS OF
APPLICATIONS WHERE YOU HAVE A
LARGE ENOUGH VOLUME OF THE
SAMPLE AND YOU WANT TO LOOK FOR
EVEN ONE TO THREE CFU, COLONY
FORMING UNITS.
SO THERE IS THIS TECHNIQUE
CALLED DRIED BLOOD SPOT.
IT USED NOW, WHERE YOU PUT A
DROP OF BLOOD, A FINGER PRICK,
AND THE BLOOD KIND OF SEEPS
THROUGH THIS FILTER PAPER AND
THEN YOU CAN SHIP THIS, THIS IS
A WAY TO TRANSPORT THAT SAMPLE
AND THEN YOU CAN SEE IN THE
MIDDLE THIS IMAGE WHERE THAT
PAPER IS PUNCHED, AND YOU CAN
ACTUALLY ELUTE DNA FROM THAT,
DETECTION OF HIV, HCV HAS BEEN
REPORTED.
THE DNA OR RNA IS ACTUALLY
PRESERVED IN THAT MATERIAL.
AND THERE'S ACTUALLY -- IT TURNS
OUT THE SCIENCE OF IT IS NOT
EXTREMELY WELL CHARACTERIZED OR
UNDERSTOOD, THERE'S SOME PAPERS
BUT NOT A WHOLE LOT AND LATELY
THERE'S BEEN MORE SORT OF
RESURGENCE OF THAT BUT WE WERE
INSPIRED BY THIS TECHNOLOGY SOME
YEARS AGO.
WE'RE USING IT IN A HOSPITAL, WE
SAW IT BEING USED, AND THE LONG
STORY SHORT, IF YOU TAKE BLOOD,
SO WHAT WE DO IS WE TAKE BLOOD,
WE DO A DRYING PROCESS, AND
THOSE DETAILS ARE PUBLISHED NOW
MORE RECENTLY, AND THEN YOU
DO -- SO YOU CREATE A SOLID
MATRIX OF DRIED WHOLE BLOOD THAT
HAS ITS MICRO NANOPOROUS
STRUCTURE, AND IT TURNS OUT THAT
THEN WHEN YOU ADD FLUID TO IT,
YOU CAN HYDRATE AND THE REAGENTS
IN THE FLUID CAN GO DOWN INTO
THAT MICRO NANOPOROUS STRUCTURE,
IT CAN ACCESS THE PATHOGEN, SO
THIS HAS NOW ALL CELLS, ALL
PATHOGENS, EVERYTHING THAT WAS
THERE, IT'S ALL DRIED IN THIS
MAY TMATRIX AND YOU CAN ACTUALL,
THEN, FOR EXAMPLE PERFORM LAMP
REACTION, ACCESS THE PATHOGEN,
DO THE AMPLIFICATION, AND THE
PRODUCTS ARE THEN DIFFUSED OUT
INTO THE SUPERNATANT.
SO YOU HAVE A SOLID PHASE AND A
LIQUID FADES, PHASE, AND THE LD
PHASE HAS A CLEAR SUPERNATANT
WITH THESE VISUAL READOUTS AND
THE SOLID PHASE IS WHERE THE
PATHOGEN WAS.
SO WE DID A WHOLE BUNCH OF
MATERIALS ANALYSIS, SO IT TURNS
OUT THAT THERE'S SOME LITERATURE
ON IT BUT NOT AS MUCH, AND YOU
CAN ACTUALLY THEN STUDY THE
POROSITY AS A FUNCTION OF
TEMPERATURE, YOU CAN LOOK AT THE
SIZE OF THE PARTICLES, THE SIZE
OF THE DIFFERENT ENTITIES AS
THEY'RE DRIED AND THEN CAN YOU
DO MORE FUNDAMENTAL STUDIES TO
ALSO EXTRACT OUT THIS FEATURE
SIZE IN THIS 3D MATRIX AFTER
THERMOLYSIS, AFTER DRYING, SO
WE'VE PUBLISHED ALL OF THAT.
LONG STORY SHORT, WE ALSO SHOWED
THAT THE INHIBITORS OF THE
REACTION, INHIBITORS OF PCR
ENZYMES OR LAMP ENZYMES SUCH AS
HEMOGLOBIN OR OTHER IGG, THEY
ACTUALLY GET TRAPPED INTO THE
SOLID MATRIX, AND THAT'S THE KEY
HERE, AND THIS IS WHY THE DRIED
BLOOD SPOT WORKS.
THAT THE INHIBITORS IN THE WHOLE
BLOOD, THEY ACTUALLY GET LOCKED
OR INACTIVATED, AND THEY DON'T
RE-SUSPEND AND THEY DON'T GET
REACTIVATED UNTIL MUCH LATER IN
TIME, SO WE SHOWED THAT ACTUALLY
BY DOING LOTS OF EXPERIMENTS
THAT PROVE THAT -- I WON'T GO
THROUGH THE VERY DETAILS HERE
BUT THE FACT THAT YOU ACTUALLY
DON'T SEE THE HEMOGLOBIN OR THE
IGG AFTER THE HEATING CONDITIONS
AT DIFFERENT POINTS IN TIME, SO
YOU SEE THIS CURVE ON THE VERY
RIGHT, YOU SEE THAT THE
CONCENTRATIONS ARE VERY, VERY
LOW.
IN THE ONES THAT WERE TREATED.
AFTER SOME TIME, IF YOU START TO
WAIT, THEN YOU WILL ACTUALLY SEE
THAT NUMBER COME UP.
SO OVER TIME, THOSE INHIBITORS
START TO GET RELEASED BUT IN THE
TIME OF, LET'S SAY, EVEN UP TO
AN HOW T HOUR, THEY STILL STAY D
IN THAT MATRIX.
WE DID THIS LIQUID EXTRACTION
SURFACE ANALYSIS MASS SPEC TO
PROVE THAT IF YOU DO A MASS SPEC
ON THE SOLID STRUCTURE, YOU SEE
THAT THE SOLID PART, THE SUPER
NATANT ACTUALLY DOESN'T HAVE ANY
SUPERNATANT AFTER THREE HOURS.
AFTER SIX HOURS, YOU START TO
SEE THE PEAKS IN THE SUPERNATANT
BUT IN THE DRIED BLOOD MATRIX
HERE IN THE BOTTOM RIGHT, YOU
CAN SEE ALL OF THE PEAKS FOR THE
HEME.
SO THE SUPERNAY AT THE PRESENT
TIME DIDN'T HAVE THE INHIBITORS,
THE DRIED MATRIX HAS THE
INHIBITORS LOCKED THERE.
SO THIS IS SOMETHING VERY
EXCITING, AND WE SHOWED THAT YOU
CAN ACTUALLY THEN TAKE ABOUT AN
800 MICRO LITER OF WHOLE BLOOD,
WHICH 1 ML IS WHAT'S USED FOR
INFANTS, AND THIS IS MRSA, EVEN
THE ORANGE CURVES HERE, THE
ORANGE BARS ARE ONE CFU PER 800
MICRO LITERS OF BLOOD.
THESE WERE SPIKE SAMPLES.
YOU SEE THIS IS MSSA, THIS IS
E. COLI, AND THIS IS A FUNGUS.
SO THIS THING ACTUALLY WORKS
VERY WELL AND WE'RE VERY EXCITED
ABOUT THE POTENTIAL OF THIS.
AT THIS POINT, THE WAY THIS WAS
DONE WAS IN VIALS BY SPLITTING
THE SAMPLE INTO SMALL VOLUMES,
AND THEN WE DID A CLINICAL STUDY
AT CARLE TO GET PATIENT BLOOD
SAMPLE.
THIS WAS HARD TO DESIGN, BUT
ESSENTIALLY A PATIENT'S BLOOD IS
TAKEN, WE ALSO GET A SAMPLE, AND
THEN WE WOULD WAIT TO FIND OUT
WHAT THE PATHOGEN WAS, AND THEN
WE WOULD LOOK FOR THAT PATHOGEN
IN THAT BLOOD, AND THIS IS DATA
SHOWING THAT, THAT WE WERE ABLE
TO DETECT E. COLI POSITIVE EVERY
TIME.
THE NUMBER HERE, 4 OUT OF 8 IS
ESSENTIALLY SAMPLES THAT WERE
SPLIT.
WE WERE DOING -- TAKING A
SAMPLE, SPLITTING IT INTO
8 SUBSAMPLES.
AND HERE YOU SEE OF COURSE WITH
OUR TECHNIQUE, THE BIPHASIC, YOU
CAN GET THE ENTIRE PROCESS TAKES
2 1/2 HOURS FROM LITERALLY
GETTING THE SAMPLE TO RESULT.
AND OF COURSE IN THIS PARTICULAR
CASE, THE CULTURE PLUS PCR WAS
TAKING SOMETHING IN THE ORDER
OF -- FROM 10 HOURS ALL THE WAY
UP TO A FEW DAYS, DEPENDING ON
THE NUMBER THAT WAS THERE.
SO WE'RE VERY EXCITED ABOUT THIS
TECHNIQUE, BUT WHAT IS NEEDED
NOW TO SCALE THIS UP TO FIVE ML,
AND THAT'S WHAT WE'RE DOING NOW.
SO THROUGH THE TALK I'LL SHOW
YOU RESULTS THAT ARE VERY RECENT
OR ONGOING, BUT THAT'S THE
DIRECTION WE'RE GOING.
OUR VISION IS TO -- WHAT THESE
WONDERFUL STUDENTS WILL
ACCOMPLISH BEFORE THEY GRADUATE
IS TO TAKE 5ML TUBE AND ACTUALLY
MULTIPLE TUBES AND WE WANT TO BE
ABLE TO LOOK FOR GRAM POSITIVE
OR GRAM-NEGATIVE AND ALSO
SPECIFIC PATHOGENS.
BUT CERTAINLY HERE MICROFLUIDICS
AND HOW YOU -- I HOPE THESE
VIDEOS WORK THROUGH THE TALK.
I JUST TESTED THEM A FEW MINUTES
AGO.
SO THE IDEA WE WANT TO TAKE THE
5MLs OF BLOOD AND ESSENTIALLY
PICKS LATE IT AND HAVE EACH
PIXEL BE DRIED AND PERFORM THIS
BIPHASIC REACTION IN EACH PIXEL.
SO WE'RE VERY EXCITED AND LOOK
FORWARD TO PUSHING THIS FORWARD.
OVER THE YEARS, WE'VE ALSO
PERFORMED -- THERE WAS A GREAT
TALK JUST A LITTLE WHILE AGO IN
THE RAPID FIRE SESSION ALSO,
T-LAMP FOR SARS-COV-2.
THIS WAS THE SPRING OF 2020, WE
ALSO DESIGNED OUR OWN LAMP
PRIMERS.
THEY ACTUALLY WEREN'T AVAILABLE
AT THAT TIME.
BUT THEN THEY BECAME AVAILABLE
VERY QUICKLY AFTER THAT AND WE
WERE ALSO ABLE TO SHOW -- AGAIN
MULTIPLE GROUPS HAVE PUBLISHED
THIS.
I THINK THERE'S A LOT OF
POTENTIAL IN THESE POINT OF CARE
DIAGNOSTICS WITH CELL PHONE
CAMERAS, ADDTIVELY -- 3D PRINTED
CARTRIDGES, AND WE WERE ABLE TO
SHOW THAT YOU CAN GET REALLY
GOOD RESULTS FROM SALIVA, AND
FROM A NASAL SWAB.
AND I THINK THIS IS IMPORTANT TO
JUST BE PREPARED FOR THE NEXT
TIME, HOPE PLI THERE'S NOT A
NEXT TIME BUT CERTAINLY IF THERE
IS, WHETHER IT'S H5N1 OR OTHER
VIRUSES.
WE'VE WORKED ON THIS AND DONE
MULTIPLE GENERATIONS OF THIS.
THE FIRST WAS FROM 2020, THEN WE
TRY TO CONTINUE TO AUTOMATE THAT
AND THE LAST ONE WE PUBLISHED
MOST RECENTLY WAS ACTUALLY FOUR
TARGETS, FLU A, FLU B, RSV AND
COVID, WITH TWO CONTROLS, SO I
BELIEVE THIS ACTUALLY IS
POSSIBLE, AND NOW IT'S A MATTER
OF REALLY SOMEONE MAKING IT
THEIR LIFE, TO ACTUALLY MAKE
THIS HAPPEN, START A COMPANY,
WORK WITH MANUFACTURERS, WORK ON
ALL OF THE COST ISSUES, WORK ON
THE SPOTTING OF THE PRIMERS AND
ALL THE PRACTICAL ISSUES, BUT I
BELIEVE THIS IS ABSOLUTELY
POSSIBLE WITH I THINK A LOW
ENOUGH COST.
BUT CERTAINLY HERE, NIBIB AND
THE RADX PROGRAM WAS PHENOMENAL
TO KIND OF PUSH EVERYTHING
FORWARD AND THAT CRISIS, OF
COURSE, REALLY CREATED A LOT OF
OPPORTUNITIES, BUT I THINK WE
NEED TO FIND A WAY TO KEEP THAT
LEVEL OF MOMENTUM EVEN WHEN
THERE'S NO CRISIS.
EVERYONE IN THE COUNTRY HAS
HEARD ABOUT PCR AFTER COVID BUT
I JUST WANT TO QUICKLY SHOW
THIS.
IF YOU LOOK AT WHAT PCR DOES AND
ITS PROS AND CONS, AND IF YOU
LOOK AT WHAT RPA, FOR EXAMPLE,
IS ONE APPROACH OR LAMP IS
CERTAINLY COMMERCIALLY
AVAILABLE.
THE IDEAL ASSAY IS STILL AT ROOM
TEMPERATURE, LESS THAN 10
MINUTES, TRULY FROM SAMPLE TO
RESULT, YOU KNOW, HIGH
SENSITIVITY, PCR LEVEL, YOU WANT
SINGLE MOLECULE, ONE MOLECULE
PER MICRO LITER OF THE REACTION,
FOR EXAMPLE, HIGH SPECIFICITY,
ALL OF THE THINGS THAT ARE HERE
IN YELLOW.
THIS DOESN'T EXIST TODAY.
IF SOMEONE CAN MEET THAT NEED,
THERE'S STILL AN OPPORTUNITY AND
I KNOW MANY OF OUR COLLEAGUES
AND MYSELF ARE WORKING TOWARDS
THAT.
SO HERE WE ARE VERY EXCITED
ABOUT A RECENT DEVELOPMENT USING
CRISPR TECHNOLOGY BUT A
CRISPR/CAS CADE ASSAY.
THIS HERE IS A SINGLE CRISPR
REACTION.
THIS WAS WHAT WAS PUBLISHED FROM
MIT, BERKELEY AND MIT
RESPECTIVELY.
BUT THE IDEA THAT YOU HAVE A
CRISPR ENZYME, THE GUIDE RNA
HERE, YOU DESIGN TO BE SPECIFIC
TO, LET'S SAY, A TARGET, SO YOU
BRING A TARGET.
ONE OF THESE STRANDS WILL BIND
WITH THE GUIDE RNA.
IT ACTIVATES THIS CRISPR, AND
THIS CRISPR THEN, CAS12, WILL
START TO CHOP OFF SINGLE
STRANDED DNA.
THAT'S KIND OF WHAT THE CRISPR
WOULD DO.
IF YOU HAVE A FLUOROPHORE, IT
CHOPS OFF THE SINGLE STRAND AND
YOU GET A FLUORESCENT SIGNAL.
SO IT BECOMES AN INDICATOR OF
THE PRESENCE OF THAT TARGET DNA.
SO THIS IS GOING TO BE -- THE
KINETICS ARE LINEAR HERE.
YOU CAN GET A SIGNAL BUT FOR
VERY LOW NUMBER ONE COPY, LET'S
SAY ONE TO THREE COPIES, IT WILL
TAKE A LONG TIME.
AND IT WON'T WORK IN THE CURRENT
SETTING, ESPECIALLY AT POINT OF
CARE.
SO WHAT YOU END UP DOING IN MOST
OF THESE APPROACHES IS YOU HAVE
TO DO A PREAMPLIFICATION.
IF YOU HAVE TO DO A
PREAMPLIFICATION WITH LAMP OR
SOME OTHER TECHNIQUE, THEN IT
JUST KIND OF DEFEATS THE PURPOSE
BECAUSE IT'S ADDING ANOTHER 20
MINUTES, YOU MIGHT AS WELL JUST
USE LAMP.
AND THE USE OF CRISPR ADDS A
LITTLE BIT OF SPECIFICITY BUT
IT'S NOT WORTH IT.
ACTUALLY I THINK THAT'S BEEN
PROVEN NOW, AND SHOWN AND
EVERYONE BELIEVES THAT AND THE
COMPANIES THAT WERE STARTED SOME
YEARS AGO TO DO THAT ACTUALLY
HAVE ALL CHANGED THEIR BUSINESS
PLAN AND DIRECTION.
WHAT YOU NEED IS SOME SORT OF AN
AMPLIFICATION REACTION IF YOU'RE
GOING TO USE THE CRISPR/CAS
CADE, SO THIS IS AN APPROACH
WHERE YOU HAVE TWO SYSTEMS.
YOU HAVE THE FIRST SYSTEM CALLED
CAS12, THE TARGET DNA, AND THEN
WHAT YOU DO IS YOU ALSO HAVE
A -- WHAT WE CALL A BLOCKED
NUCLEIC ACID THAT HAS REGIONS OF
SINGLE STRANDED, LET'S SAY THESE
LOOPS, SO BASED ON THIS TARGET
BINDING WHEN THIS ENZYME GETS
ACTIVATED, IT WOULD CUT OFF THIS
REGION AND THIS REGION, WHICH
WILL RELEASE A NUCLEIC ACID.
THIS UNBLOCKED NUCLEIC ACID
WOULD THEN ACTIVATE A SECOND
SYSTEM.
THE SECOND SYSTEM THEN HAS THIS
CYCLICAL, CASCADE EFFECT BY ALSO
CUTTING OFF THAT BLOCKED NUCLEIC
ACID AND ALSO THE REPORTERS,
BOTH THE ENZYMES, ACTIVATED
ENZYMES CAN ALSO START TO CLEAVE
THIS, SO THIS WOULD BE AN
EXPONENTIAL RE'TION.
THIS WOULD HAPPEN VERY FAST, IT
DOESN'T NEED THE ENZYMATIC, THE
ACTUAL -- LIKE A POLYMERASE
BUILDING UP THE MOLECULE.
SO THIS IS PRETTY EXCITING, A
LOT OF WORK GOING ON ON THIS,
HAS BEEN NOW A HANDFUL OF
PAPERS, ONLY FOUR OR FIVE ONLY,
BUT I'LL JUST SHOW YOU THIS IS
SUBMITTED, SO -- WE ACTUALLY
SHOWED YOU CAN DESIGN THIS OR
FUNCTION WHERE YOU HAVE THE
BLOOD PATHOGENS, IN THIS CASE
MRSA, MSSA, E. COLI AND HBV.
WE ACTUALLY SHOWED THAT IF ANY
ONE OF THOSE IS PRESENT, YOU GET
A POSITIVE SIGNAL.
SO IT'S LIKE AN OR FUNCTION, AND
ESSENTIALLY A PANEL, YOU CAN
DESIGN THIS FOR A LARGER NUMBER,
WE SHOWED IT WITH 4, SO IF ANY
OF THESE PATHOGENS ARE IN THAT
SAMPLE, YOU GET A SIGNAL.
THE CHALLENGE IS THAT THE
SIGNAL-TO-NOISE RATIO HAS TO BE
EVEN HIGHER.
I THINK THIS IS MAYBE
ACCEPTABLE, BUT IF YOU REALLY
WANT TO TRANSLATE AND
COMMERCIALIZE THIS, THIS IS NOT
GOOD ENOUGH.
1.4 IS NOT GOOD.
SO YOU HAVE TO WORK ON REDUCING
THE BACKGROUND, BECAUSE WHAT
HAPPENS IS IF THERE IS
NONSPECIFIC CLEAVAGE OF THOSE
SINGLE STRANDED REGIONS BY THE
ENZYME OR THE BLOCKED NUCLEIC
ACID IS NOT ALWAYS A PERFECT
SWITCH AT THE TEMPERATURE YOU'RE
OPERATING AT.
SO THERE'S A MELTING CURVE AND
MELTING CURVE HAS TAILS AND FACT
IS THAT ENOUGH OF THE MOLECULES
ARE ACTUALLY UNBLOCKED SO THE
ENZYME GETS ACTIVATED BEFORE YOU
WANT TO.
SO I THINK THAT'S THE KEY
TECHNICAL CHALLENGE THAT NEEDS
TO BE ADDRESSED.
BUT THIS IS VERY EXCITING AND
ACTUALLY WE'RE WORKING ON
COMMERCIALIZING IT THROUGH A
COMPANY CALLED VEDABIO THAT HAS
THE I.P. AROUND THIS AND IS
CONTINUING TO PUSH THIS FORWARD
AND THIS IS A WHOLE STORY OF
ITSELF BUT IT'S VERY EXCITING
AND IT'S PRETTY RECENT.
LET ME TALK ABOUT OTHER
TECHNOLOGIES THAT WE ARE VERY
INTERESTED IN.
SO CELLS AND MOLECULES FROM A
DROP OF BLOOD FOR THE IMMUNE
STATUS.
SO WHETHER IT'S SPECIFIC TYPES
OF CELLS OR DNA, RNA, OR
PROTEINS, SO WE'VE HAD THIS
PLATFORM THAT WEE HAVE BEEN
WORKING ON AND REFINING AND
IMPROVING FOR A WHILE.
THIS WAS ORIGINALLY LICENSED TO
THE COMPANY I'LL MENTION NEXT.
THE IDEA HERE IS PUTTING CULTURE
COUNTER, A VERY WELL ESTABLISHED
TECHNOLOGY, ON A CHIP BUT PUT
MULTIPLE CULTURE COUNTERS AND
BUILD THE IMMUNOCAPTURE REGION
IN BETWEEN.
SO THE HAVE THE CULTURE COUNTER
HEAR, HEAR, WHICH CAN COUNT
CELLS AND PERHAPS TELL YOU SOME
OF THE TYPES OF THE WHITE BLOOD
CELLS AND THEN THERE'S A COUNTER
AT THE EXIT OF THIS AND IN
BETWEEN, YOU HAVE THIS HIGH
SURFACE AREA TO VOLUME RATIO,
WHERE ANTIBODIES ARE ATTACHED.
THIS IS INSPIRED FROM WORK WHERE
THEY DID THE CB CCAP TOUR ON
THESE POSTS AND THEN WE BUILT
OUT THE OTHER PARTS WHICH IS
THIS PROCESSING OF WHOLE BLOOD
AND LYSING OF RED BLOOD CELLS
AND PURIFICATION AND, TRACKS OR
COLLECTION OF THE WHITE BLOOD
CELLS.
SO WHOLE BLOOD COMES IN, GOES
THROUGH A MICROFLUIDIC DEVICE,
THERE IS A FLUID SHEET COMING
FROM THE SIDE, THE MIDDLE PART
HERE IS WHOLE BLOOD AND AFTER A
FEW SERPENTINE TURNS, YOU CAN
SEE THE BLOOD WILL START TO LOOK
TRANSPARENT BECAUSE THE RED
BLOOD CELLS ARE GETTING LYSED
AND THERE ARE RED BLOOD CELLS
GETTING COVERED.
THEY'RE A THOUSAND TIMES LESS IN
NUMBER SO THAT'S WHY YOU CAN
BARE LEABARELY SEE THEM BUT THEE
THERE, THEY GO THROUGH THE
COUNTER, CAPTURE, COUNTER.
SO USING THIS, WE HAVE DONE A
RANGE OF THINGS I'LL SHOW YOU.
WE HAVE DONE CAPTURE AND
EXPRESSION LEVEL OF
CD64 EXPRESSING NEUTROPHILS.
THIS IS A MARKER FOR
INFLAMMATION AND FOR SEPSIS, SO
WHEN PATIENTS ARE PROGRESSING
THROUGH THE STAGES OF
INFLAMMATION, THEIR
CD64 EXPRESSION HAS SHOWN TO BE
HIGH SO WE DO THAT FROM IN OUR
DEVICE.
YOU CAN SEE ON THE TOP HERE IS
THE ENTRANCE AND EXIT COUNTS
ESSENTIALLY AND THE DIFFERENCE
OF THOSE TWO COUNTS IN THIS CASE
GIVES YOU THE GRANULOCYTES, THE
MONOCYTES.
THE X AXIS IS FROM A FLOW
CYTOMETER AND THE Y AXIS IS FROM
OUR CHIP.
SO THE SAMPLE IS SPLIT.
THE OTHER PART OF THE SAMPLE IS
RUN THROUGH A COMMERCIAL FLOW
CYTOMETER AND YOU GET PRETTY
GOOD CORRELATION OF THINGS RUN
IN THE LAB AND BY STUDENTS.
THE DEVICE IS OPTIMIZED TO GET
THE RIGHT SHEER STRESS OF THE
CHAMBER WALL, AND YOU CAN
ACTUALLY TRACK EVEN PATIENT AS
THEY ARE IN THE HOSPITAL, THEY
WERE ABLE TO GET PATIENT SAMPLES
THROUGH THE HOSPITAL, THROUGH
THEIR STAY, AND YOU CAN TRACK
THEIR CELL COUNT AT A POINT OF
CARE.
WE WERE ABLE TO TAKE THE SAME
TECHNIQUE AND WORK WITH
PROFESSOR HAHN IN SEMI INDUSTRY
AND BUILD A CULTURE COUNTER THAT
ALSO HAS A DIFFERENCE IN THE
ELECTRICAL SIGNATURE.
SO IF YOU WERE TO MAKE BEADS
THAT WERE ABOUT THE SAME SIZE,
BUT HAD A DIFFERENT ELECTRICAL
SIGNATURE, YOU COULD ACTUALLY
MULTIPLEX.
TODAY IT CANNOT BE MULTIPLEXED.
YOU SEE AN EXAMPLE OF THREE
TYPES OF BEADS ABOUT THE SAME
SIZE, 11 TO 13 MICRONS IN
DIAMETER BUT THEIR COMPOSITION
IS DIFFERENT.
WITH DIFFERENT PERCENT OF THE
HYDROGEL THAT WAS USED TO
SYNTHESIZE THIS AND YOU CAN SEE
A VERY DIFFERENT IMPEE DANCE
SIGNAL AS THE BEADS FLOW BY THE
COUNTER.
HERE IS THE ACTUAL PULSES, THE
THREE DIFFERENT AMPLITUDE
PULSES.
SO NOW THE BEADS ARE USED TO
CAPTURE A BIOMOLE KEUL FROM THE
SAMPLE.
WE CAN THEN DESIGN THE CHEMISTRY
TO CAPTURE THE BEADS ON THE
POSTS AND ALSO BE ABLE TO USE
THE SAME EXACT PLATFORM FOR RNA
AND DNA DETECTION AS WELL AS --
OR PROTEIN DETECTION.
SO THAT'S THE GOAL HERE, WE
DEMONSTRATED THAT WITH PROTEINS
AND ALSO WITH SOME MICRORNA, AND
WHAT'S EXCITING ABOUT THIS IS
FROM THE SAME BLOOD SAMPLE, SO
YOU CAN ACTUALLY GET -- YOU CAN
CAPTURE CELLS AND IF YOU HAVE
THESE BEADS, THEN YOU CAN ALSO
IN THE SAME SAMPLE BE ABLE TO
DETECT OTHER BIOMARKERS.
SO WE'RE KIND OF WORKING TOWARDS
EX-PANNING THAT.
BUT WHERE THIS IS ALL LEADING TO
IN PARALLEL WHAT WE HAD ALSO
BEEN WORKING ON, THIS IS A
SEPSIS BIOMARKER STUDY.
SO SEPSIS IS A VERY COMPLICATED
CONDITION.
I WON'T GET INTO THE BIOLOGY OF
IT, NOT THAT I CLAIM TO KNOW IT.
BUT THERE'S A LOT OF PAPERS OUT
THERE.
IT'S A HIGHLY COMPLEX PROCESS
WITH MULTIPLE STEPS THROUGH IT,
WHERE THE PATIENT EXHIBITS A
PRO-INFLAMMATORY CASCADES AND
STAGE AND AN ANTI-INFLAMMATORY
STAGE.
SO WHAT WE DID WAS WORKING WITH
CARLE SOME YEARS AGO, IT'S BEEN
ABOUT SEVEN, EIGHT YEARS, WE
ACTUALLY PLANNED KIND OF A BIG
STUDY WHERE WE LOOKED AT THE
LITERATURE THAT WAS THERE, AND
SEPSIS HAS NO ONE BIOMARKER,
IT'S KNOWN ALREADY.
IT'S NOT LIKE FOR HEART
CONDITION, YOU HAVE TROPONIN.
IT'S A SINGLE BIOMARKER THAT'S
HIGHLY CORRELATED TO WHAT
HAPPENED.
SEPSIS HAS NO ONE BIOMARKER.
SO WE LOOKED AT ALL THESE
PRO-INFLAMMATORY MARKERS, THERE
ARE SOME NEUTROPHILS IN THERE,
CD64, SO WE DESIGNED THIS STUDY,
GOT CARLE TO DO THAT, DR. KAREN
WHITE AND ANOTHER, DR. JAMES
KUMAR.
AND WE WOULD ALSO GET THE EMR
DATA FOR THOSE PATIENT FOR THEIR
ENTIRE STAY.
THIS WAS A VERY INTERESTING
COMPLEX LONG PROCESS.
THE ADJUDICATION PROCESS IS
REALLY INTERESTING.
AND NOT VERY WELL-DEFINED FOR
SEPSIS.
SO WE KIND OF WORKED THROUGH
THAT, SOME OF THIS WORK IS
PUBLISHED, AND THEN WE APPLIED
MACHINE LEARNING ALGORITHMS,
WHICH IS NOW A.I., WITH
PROFESSOR ZU -- STATISTICS
DEPARTMENT AT UIC AND AT THE END
OF THE DAY, THE BOTTOM LINE IS
THIS, YOU HAVE ON THE X AXIS ALL
OF THESE PARAMETERS, MANY OF
THEM ARE MEASURED FROM THE
BLOOD.
AND THEN THERE IS THE ONES FROM
EMR.
AND THE Y AXIS IS THE NORMALIZED
FEATURE COEFFICIENT WHICH IS THE
IMPORTANCE OF THAT PARAMETER TO
THE END OUT COME.
YOU CAN SEE THERE IS MULTIPLE
PARAMETERS.
SO I THINK THIS IS IMPORTANT.
AND THEN YOU CAN -- THIS CURVE
IS REALLY TELLING, IS THAT IF
YOU NOW WERE TO RUN THAT SAME
DATA AND RUN IT AGAINST TODAY'S
STANDARD, WHICH IS A SOFA OR
QSOFA SCORE WHICH THE PHYSICIANS
DO, YOU GET THIS ORANGE AND THE
PURPLE CURVE, THESE TWO.
AND HERE, THE AUC IS ABOUT .5.
SO IT'S A COINS COIN TOSS BASIC.
THAT'S WHAT'S HAPPENING TODAY
BECAUSE YOU DON'T HAVE THE BLOOD
BASE INFORMATION THAT WE CAN
INFORM THE PHYSICIANS WITH.
BUT AS YOU START TO ADD THESE
BIOMARKERS FROM BLOOD, YOU CAN
GET TO, IN THIS CASE .8 AND THIS
DATA IS NOW A FEW YEARS OLD.
SO THE FACT IS THAT IF YOU TAKE
THE EMR DATA BUT ADD BIOMARKER
DATA, YOU CAN REALLY INCREASE
THE PREDICTIVE POWER OF THIS
MODEL.
IF YOU WERE TO TEST MULTIPLE
PROTEINS, FIVE OR SIX MARKERS,
LET'S SAY.
SO THIS IS WHAT THEN ALSO BECAME
THE BASIS OF A COMPANY CALLED
PRENOSIS .
IT'S A VERY INTERESTING STORY
AND I GIVE ALL THE CREDIT TO THE
CO-FOUNDER, MY PH.D. STUDENT
POSTDOC BOBBY REDDY.
INTERESTINGLY ENOUGH, AS WE
STARTED TO COLLECT HEME, WE
STARTED TO COLLECT BLOOD SAMPLES
TO DO THE TEST ON THE DEVICE.
I WAS VERY EXCITED ABOUT THE
DEVICE.
AND ALONG THE WAY YOU KNOW THE
POWER, HERE THE GOLD MINE IS THE
BLOOD SAMPLES, ALL OF THE OTHER
THINGS YOU CAN MEASURE FROM
THAT.
SO THEN HE MOVED THE COMPANY IN
A DIFFERENT DIRECTION, WHICH IS
TO BUILD A BIG DATASET
ESSENTIALLY FROM BLOOD SAMPLES
OF MULTIPLE PROTEINS, AND THEN
APPLYING MACHINE LEARNING AND
A.I. TO THAT, AND THEY GOT THE
FIRST FDA APPROVAL FOR AN
AI-DRIVEN TEST TO PREDICT SEPSIS
IN HOSPITALS.
ESSENTIALLY IT GIVES A RISK
SCORE, THIS WAS IN APRIL.
SO THE VISION IS STILL WHAT'S ON
THE LEFT, WHICH IS YOU HAVE A
DEVICE, YOU MEASURE -- YOU TAKE
A DROP OF BLOOD AND YOU MEASURE
THESE FOUR OR FIVE PARAMETERS,
BUT THEN YOU COMPARE THAT DATA
TO THIS BIG DATASET THAT'S IN
THE BACKGROUND.
AND THEN YOU PROVIDE A RISK
SCORE TO INFORM THE PHYSICIANS
AS TO WHO TO PAY ATTENTION TO
FIRST OR NOT.
SO HOPEFULLY THIS IS MOVING
FORWARD.
YOU CAN LOOK UP THE NEWS ON
THIS, ROCHE IS ACTUALLY
MARKETING THIS PRODUCT AS PART
OF THEIR PLATFORM.
AND IT'S VERY EXCITING.
AND MULTIPLE HOSPITALS NOW HAVE
ADOPTED THIS.
OKAY.
SO IN THE REMAINDER OF THE TIME,
I KNOW I HAVE MAYBE A LITTLE BIT
OF TIME BUT I'M RUNNING SHORT,
SO I WILL WANT TO LEAVE TIME FOR
Q & A.
I'LL JUST GO THROUGH THIS PART
QUICKLY.
LET ME JUST SKIP THROUGH.
WE'RE VERY INTERESTED ALSO IN 3D
BIOPRINTING AND BUILDING -- LIKE
I'M INTERESTED IN BUILDING
THINGS SO WE WANTED TO ALSO
BUILD THINGS AT THE MICRO
NANOMACKO SCALE, SO BIOPRINTING
IS SOMETHING WE'VE BEEN WORKING
ON FOR SOME TIME.
AND AGAIN THIS IS NOW, THERE'S
SO MANY PERMUTATIONS AND
VERSIONS OF THESE BIOPRINTERS.
THERE'S A LOT OF WORK ON T A LOT
OF GREAT, GREAT WORK, RIGHT?
SO WE HAVE PUBLISHED SOME STUFF
OVER THE YEARS AND WE CAN MAKE
THESE HYDROGEL STRUCTURES THAT
CAN BE THEN USED TO FORM TISSUES
OF WELL-DEFINED FORMS
ESSENTIALLY, SO SHAPES.
SO IN THIS CASE, WHAT YOU SEE IS
TOP VIEW HERE OF A MUSCLE --
WHAT WE CALL A MUSCLE STRIP
THAT'S ANCHORED BETWEEN TWO
POSTS THAT ARE VERTICALLY COMING
ON THE SCREEN HERE.
YOU CAN ALSO FORM A MUSCLE RING.
IF YOU HAVE A MOLE HERE THAT
BLOCKS THAT, WE TAKE OPT
GENETICALLY TRANSFECTED SKELETAL
MUSCLE CELLS, ADD FIBRIN AND
COLLAGEN WITH SOME MAY TRI GEL
AND YOU CAN ESSENTIALLY, OVER
MANY HOURS, THERE'S THIS
COMPACTION AND UNDULATION
PROCESS AND THESE CELLS AND
MATRIX COME TOGETHER AND FORM A
VERY WELL-DEFINED STRIP.
THIS IS OVER SEVEN HOURS, EIGHT
HOURS, SO OVER A FEW DAYS, THIS
VERY WELL-DEFINED MUSCLE STRIP
AND SHAPE IS FORMED, AND
PROFESSOR HERSAFE IS IN THE
AUDIENCE, WE'VE COLLABORATED
WITH HIM FOR MANY YEARS.
SO WE CAN TAKE THERE PROCESS AND
WE CAN NOW TURN THIS INTO THESE
BUILDING BLOCKS THAT NOW WE
ACTUALLY TEACH IN OUR
UNDERGRADUATE LABS ACTUALLY.
SO YOU CAN BUILD THESE MUSCLE
RINGS AND STRIPS OF DIFFERENT
SHAPES OR CIRCLES.
THEY'RE REASONABLY ROBUST.
YOU CAN ACTUALLY GRAB THEM AND
THEN MOVE THEM TO ANOTHER
STRUCTURE, ANOTHER SCAFFOLD
HERE.
SO ONE OF THE STUDENTS THAT DID
THIS WORK IS AT UIUC WHICH IS
NOW AT MIT, WE TRANSFERRED THIS
TO DIFFERENT LABS.
WE CAN ALSO DO THIS ON NEURAL
TISSUE, AND THERE'S SOME
DIFFERENT PARAMETERS THERE
BECAUSE THE STIFFNESS OF THE
MATERIAL HAS TO BE LESS TO ADAPT
TO THE NEURAL TISSUE, BUT THESE
ARE RINGS THAT ARE OF MOUSE
EMBRYONIC STEM CELL DERIVED
MOTOR NEURONS THAT HAVE BEEN
COMPACTED INTO THESE RINGS AND
THEY CAN ALSO BE GRABBED AND
TRANSFERRED ON TO, LET'S SAY, IN
THIS CASE A GLASS ROD, AS YOU'LL
SEE IN JUST A LITTLE BIT, AND
THEY CAN GROW PROCESSES.
SO IT'S THESE BUILDING BLOCKS AT
THE TISSUE THEY FEEL THAT YOU
CAN BUILD AND THEN PERHAPS BUILD
HIGH ORDER STRUCTURES WITH THAT.
SO IN THE INTEREST OF TIME I'LL
MOVE THROUGH THIS FAST BUT SHOW
THAT WE'RE INTERESTED HERE IN
DEVELOPING BIOLOGICAL MACHINES,
AND THIS WAS AGAIN PART OF A
CENTER THAT MANY OF US WERE ON
INCLUDING MANU, WAS PART OF
THAT, AND THE IDEA OF BUILDING
LET'S SAY BIOMECHANICAL SOFT
ROBOTICS THAT ARE DRIVEN BY
CELLS, SO I'M SURE THIS VIDEO L
THIS IS A CROSS-SECTION VIDEO,
THE WHITISH LAYER THERE IS
SKELETAL MUSCLE TISSUE THAT HAS
CHANNEL RHODOPSIN TRANSFECTED SO
THESE ARE LIGHT SENSITIVE.
IT'S DESIGNED MECHANICALLY TO
MOVE IN ONE DIRECTION BECAUSE
YOU BREAK SYMMETRY, WALKING IN
ONE DIRECTION EVERY TIME YOU
SHINE LIGHT.
SO THE MUSCLE TWITCHES AND IT
MOVES FROM LEFT TO RIGHT IN A
PETRI DISH IN FLUID.
SO THESE KIND OF DEVICES AND
SORT OF THINKING ABOUT THIS
ENGINEERING OF BIOLOGY AT THE
SCALE I THINK WOULD BE VERY
INTERESTING.
WE HAVE CHARACTERIZED THIS, CAN
MEASURE FORCES BECAUSE YOU KNOW
THE MATERIALS WELL, AND AGAIN,
SOMETHING LIKE THIS NOW, WE'RE
DOING THIS IN OUR JUNIOR
BIOENGINEERING LAB IN THE
DEPARTMENT, AND HERE WE DID A
DLAB RANGE OF MOTICOLLABORATIOND
TO SHOW THIS SINCE HE'S HERE,
WHERE THESE STRUCTURES DO
DEGRADE OVER TIME AND THE
HYPOTHESIS WAS THAT THESE ARE
ECM PROTEINS THAT ARE BEING PRO
KBROKEN DOWN BY PROTEASES, CELLS
SECRETE THE PROTEASE, THEY
DEGRADE THE MATRIX, AND
ESSENTIALLY YOU CAN SEE OVER
TIME, ON THE RIGHT HERE EVEN
WITH THE DIFFERENT STARTING
STIFFNESS AS A FUNCTION OF TIME,
THE MUSCLE TISSUE STARTS TO
DEGRADE.
SO WE WORKED WITH MANU AND DID
SOME MECHANISTIC STUDI STU, USIG
ZYMOGRAPHY.
IF YOU ADD AN INHIBITOR LIKE
ACA, YOU CAN ACTUALLY INCREASE
THE LIFETIME SO YOU CAN CONTROL
THE LIFETIME OF THESE MUSCLE
TISSUES, IN THIS CASE,
SIGNIFICANTLY INCREASE IT WHEN
YOU ADD THE ACA, FOR EXAMPLE.
SO USING THIS MORE RECENTLY, WE
ALSO WORKED WITH JOHN RODGERS
AND WE HAVE DESIGN SO HIGHER
ORDER STRUCTURES WHICH WE THEN
DESIGNED THESE INTEGRATED
ELECTRONIC DEVICES, AND I'D JUST
LAKE TO SHOW THIS.
SO THIS IS A STRUCTURE, YOU'RE
LOOKING AT A TOP VIEW.
THERE'S TWO SETS OF MUSCLES, ONE
ON THE RIGHT, ONE ON THE LEFT,
AND WE CAN INDIVIDUALLY CONTROL
WITH THEM LATE BY SHINING LIGHT
AND CONTROLLING THAT REMOTELY
WITH AN RF SIGNAL, AND IF I
PULSE THE LEFT LEG MORE THAN THE
RIGHT LEG, THEN IT CAN TURN, SO
THIS THING CAN TURN AND WALK
THROUGH A MAZE.
AND IT'S MUSCLE-DRIVEN.
BIOLOGICALLY MUSCLE-DRIVEN.
WE CAN DO THE SAME THING WITH
NOW NEURONS AS I MENTIONED
EARLIER, AND IN THE INTEREST OF
TIME I'LL JUST SKIP THROUGH THIS
AND SHOW YOU SOME VERY RECENT
RESULTS THAT ARE NOT PUBLISHED,
THIS IS GOING OUT FOR REVIEW
VERY SOON, WHERE WE ADDED THE
NEUROMUSCULAR JUNCTION, SO WE DO
THE NEURAL TISSUE, MUSCLE
TISSUE, PUT THEM TOGETHER IN A
3D STRUCTURE THAT HAS THESE
MECHANICAL DESIGNS, AND THE
NEURAL TISSUE SENDS SIGNALS TO
THE MUSCLE, AND THE DEVICE CAN
THEN AUTONOMOUSLY MOVE, AND HERE
YOU'LL SEE SOMETHING
INTERESTING, SO THIS IS MOVING
BECAUSE OF LIGHT, BUT THEN WHEN
YOU TURN THE LIGHT OFF, IT
ACTUALLY WILL KEEP MOVING.
SO THE NEURAL TISSUE HAS BEEN
PROGRAMMED IN THIS CASE, TO KEEP
FIRING EVEN AFTER YOU TURN OFF
THAT STIMULATION OF LIGHT.
SO THERE'S SOME VERY INTERESTING
IMPLICATIONS HERE WITH
BIOLOGICAL COMPUTING AND
THINKING ABOUT BIOLOGICAL
TISSUES, NEURAL TISSUE THAT CAN
BE USED AS BIOLOGICAL
PROCESSORS, SO WE HAVE AN NSF
GRANT TO BUILD BIOLOGICAL LIVING
PROCESSORS, FOR EXAMPLE.
I DO WANT TO IN THE LAST MINUTE
SHOW YOU VERY QUICKLY THE
MEDICAL EDUCATION PIECE.
THIS IS VERY EXCITING, BUT WE
HAVE STARTED A NEW MED SCHOOL AT
UNIVERSITY OF ILLINOIS
URBANA-CHAMPAIGN, AND HERE THE
IDEA IS TRULY TO INTEGRATE
ENGINEERING AND MEDICINE
TOGETHER.
SO FOR EVERY COURSE, THERE IS
THREE COURSE DIRECTORS, THERE'S
A BASIC SCIENTIST, A CLINICIAN,
AN ENGINEER, AND ENGINEERING AND
INNOVATION IS INTEGRATED THROUGH
THE FOUR YEARS.
WE GRADUATED THREE CLASS,
THERE'S A DEAN OF THE MED
SCHOOL, NOW A SECOND DEAN,
PROFESSOR MARK COHEN, WHO'S
DOING -- ARE HIRED HIM FROM
MICHIGAN, HE'S DOING GREAT, AND
WE HOPE TO ACHIEVE FULL
ACCREDITATION SOMETIME NEXT
YEAR, BUT THIS IS I THINK,
AGAIN, A REAL FUSION OF
ENGINEERING AND MEDICINE.
AND I USUALLY SAY THAT WITH ALL
DUE RESPECT, YOU KNOW, THAT A.I.
WILL NOT REPLACE PHYSICIANS BUT
I THINK PHYSICIANS WHO DON'T
KNOW A.I. MIGHT GET A LITTLE
WORRIED, SO MAYBE THEY NEED TO
LEARN.
AND THIS IS THE IDEA, IS THAT
WHY ISN'T ENGINEERING AND
TECHNOLOGY AND A.I. AND
COMPUTING NOT INTEGRATED INTO
THE MEDICAL CURRICULUM?
SO THAT'S WHAT THE GOAL IS HERE.
IT'S A BIOENGINEERING MEDICAL
CURRICULUM REALLY ALL THROUGH
THE FOUR YEARS.
AND WE'RE ALSO VERY EXCITED
RECENTLY, I WAS PART OF THE --
PROFESSOR KELLY FROM
NORTHWESTERN IS OUR FEARLESS
LEADER AND DOING A GREAT JOB,
AND THIS IS SOMETHING THAT JUST
GOT LAUNCHED A YEAR AGO, AND I
THINK THERE'S A LOT OF
INTERESTING ANALOGIES AND
DISCUSSION, WHETHER IT'S WITHIN
NIH, OR WITHIN OUR UNIVERSITIES,
BUT THIS IS ALSO SOMETHING
THAT'S GOING TO HELP EXPAND THE
UNDERSTANDING AND KNOWLEDGE OF
INFLAMMATORY STATES THAT
UNDERLIE MANY DISEASES.
SO WITH THAT, I'LL THANK YOU.
I APOLOGIZE FOR RUNNING A LITTLE
LATE BUT THANK YOU TO NIH FOR
FUNDING OUR GROUP AND AGAIN MANY
COLLABORATORS HERE.
PROFESSOR VALERA, PROFESSOR TYRA
SAVE, JUNE CONGR KONG AND OTHER.
>> OKAY, IF YOU HAVE QUESTIONS
PLEASE COME TO THE MICROPHONE,
WE'LL GIVE DR. BASHIR A LITTLE
PIECE OF GRACE.
I'LL ASK THE FIRST ONE IF NO ONE
WILL.
SO, OKAY, RASHID, EVERYTHING IS
REALLY COOL, BUT YOU STARTED
WITH THE BLOODSPOTS AND HOW THE
DRIED BLOOD BECOMES A MATRIX
WITH THE CRACKS THAT ALLOW
TRANSPORT THAT NORMALLY WE
WOULDN'T REALLY THINK WOULD HAVE
ACCESS.
I JUST FOUND THAT THE SIMPLICITY
OF THAT QUITE BRILLIANT -- THAT
IT ENABLES THE BIOCHEMISTRY OR
THE CHEMISTRY ASSAYS, AND I JUST
AIN THINKING ABOUT THAT WAS
WONDERING ARE THERE OTHER
BIOLOGICAL MATERIALS THAT IF
THEY WERE IN A DIFFERENT PHASE
THAN WHAT WE'RE NORMALLY USED TO
USING AND WE'RE TOLD TO ONLY
KEEM THEM KEEP THEM IN A CERTAIT
WE'RE JUST MISSING THAT
OPPORTUNITY.
CAN YOU THINK OF ANY OTHER
TISSUES THAT CAN PHASE
TRANSITION THAT MIGHT BE
BENEFICIAL?
>> THAT'S A GREAT QUESTION AND I
THINK THAT'S EXACTLY THE POINT,
I MEAN EVEN IF TISSUE, HOW IT'S
PRESERVED, I MEAN IT'S SO
IMPORTANT, IN SOME SITUATIONS
YOU OF COURSE MIGHT DAMAGE SOME
TYPE OF MOLECULES, IN OTHER
CASES YOU MIGHT NOT.
SO WE WERE READING UP ON HOW TO
ACTUALLY PROCESS LARGE VOLUMES
OF BLOOD, BUT ALSO DIRECTLY FROM
WHOLE BLOOD AND NOT TO HAVE
ANY -- AND WHAT WE THOUGHT IS
THAT, LOOK, EVERYTHING WE WANT
IN BLOOD IS IN THE BLOOD, SO WHY
WOULD WE -- WHY WOULD I EVEN
SEPARATE THINGS?
IS THERE SOME WAY TO CAPTURE
WHAT'S THERE BUT HAVE ACCESS TO
IT AND PRESERVE IT.
THEN THIS DRIED BLOOD SPOT
TECHNOLOGY, THE FACT THAT IT
EXISTS, SO THE FACT THAT WAS NOT
VERY WELL UNDERSTOOD, WE
ACTUALLY GOT A PATENT ON THIS
ALSO IS THE FACT THAT YOU CAN
PRESERVE THIS AND THE INHIBITORS
ARE LOCKED AND ARE INACTIVATED
IS A MORE SCIENTIFIC TERM AND
HENCE, YOU KNOW, YOU CAN STILL
ACCESS THE PATHOGEN THROUGH THE
POROSITY AND GET THE
AMPLIFICATION GOING AND THE
PRODUCTS CAN GO OUT IN THE
SUPERNATANT.
THIS REALLY HADN'T BEEN SORT OF
EXPLORE AND LOOKED AT IT THAT
WAY.
WE WERE THINKING OF ADDING
BUBBLES TO TO INCREASE THE
VOLUME INSIDE, BUT IT TURNED OUT
THAT WASN'T EVEN NEEDED BECAUSE
THE POROUS STRUCTURE THAT EXISTS
ALLOWS THAT ACCESS.
>> THERE'S ONE CLOSING QUESTION
FOR YOU.
I ALSO KNOW YOU'VE TAKEN SOME OF
YOUR TECHNOLOGY AND STARTED
COMPANIES THAT HAVE WORKED IN
DEVELOPING COUNTRIES, A LOT
OF -- INTERNATIONAL PLACES.
I WONDER IF YOU CAN TALK ABOUT
THE DIFFERENCES, I DON'T WANT TO
SAY CHALLENGES DIFFERENCES OF
STARTING COMPANIES AND
DEVELOPING -- OR NOT COMPANY
BUT -- RUNNING A COMPANY THERE
VERSUS USING THE U.S. HEALTHCARE
SYSTEM.
>> THAT'S A VERY IMPORTANT
POINT.
SO ONE COMPANY AT THE END OF THE
DAY, THEY ENDED UP LICENSING THE
TECHNOLOGY TO A BIG
PHARMACEUTICAL BUT DIDN'T MEET
THEIR INITIAL GOAL WAS THIS
GLOBAL HEALTH DIAGNOSTICS FOR
HIV AND ONE OF THE FLOW
CYTOMETER THING THAT I SHOWED,
IT WAS SIMILAR TO THAT, THE IDEA
OF COUNTING WHITE BLOOD CELLS,
CD4 AND CD8 WHITE BLOOD CELLS,
BUT THE REALITY IS THAT THE
MANUFACTURING WAS TOO EXPENSIVE.
SO YOU CANNOT BUILD THINGS IN
THE U.S. OR EUROPE AND SELL THEM
THERE.
FOR HIV DRUGS, IT WORKED BECAUSE
IT WAS SUCH A MASSIVE SCALE, AND
THERE WAS A LOT OF SUPPORT
INITIALLY AND THERE WAS A WILL
FROM THE GOVERNMENTS TO ACTUALLY
JUST DO THAT.
SO THE COST OF DRUGS WAS LOW
ENOUGH TO DO THAT, SO THE FACT
IS THAT MANY OF US HAVE WORKED
ON AND ARE VERY UNSPA UNSPIRED K
ON GLOBAL HEALTH TECHNOLOGIES.
IN MOST CASES THE BUSINESS MODEL
DOESN'T WORK.
SO WE HAVE TO DO THE
MANUFACTURING THERE, WE HAVE TO
DO THE MANUFACTURING IN THOSE
COUNTRIES AND LOWER THAT COST
AND USE TO EVEN SORT OF HELP THE
ECONOMY SO TO SPEAK.
BUT I THINK SOME OF THAT
TECHNOLOGY IS, YEAH, THE COST
MODEL THAT WAS MENTIONED
EARLIER.
GLRS WHAT WAS SAID ON THE
INDUSTRY PANEL, YOU WERE NODDING
HARD ABOUT THINKING ABOUT
MANUFACTURING EARLY ON.
>> ALSO THINGS CHANGE, ONE MORE
POINT, SO THE GOLD STANDARD FROM
WHO ALSO AND IN THE U.S. WAS
DETECTION OF CD4 T CELLS.
WELL, THE FACT IS, THAT WAS
BECAUSE THE VIRAL DETECTION
TECHNOLOGIES WEREN'T ADVANCED
ENOUGH, BUT IF YOU CAN JUST
COUNT THE HIV VIRUSES, WHY WOULD
YOU LOOK AT CD4 EVEN?
PCR AND THESE TECHNIQUES GOT
BETTER AND BETTER, WHO CHANGED
ITS STANDARD.
THEY SAID WE'RE NOT GOING TO
LOOK AT CD4 ANYMORE, WE WANT THE
VIRAL LOAD.
WELL THERE YOU GO, OUR WHOLE
THING WAS BASED ON CD4.
SO I THINK THINGS ALSO CHANGE
AND YOU HAVE TO BE AWARE OF THE
MARKET DYNAMICS OR THE WORLD AND
ADAPT.
>> THANK YOU SO MUCH FOR THIS
INSIGHT.
PLEASE GIVE DR. BASHIR A HAND.
[APPLAUSE]
>> ALL RIGHT, WOW, THAT WAS
GREAT.
WE ARE JUST A FEW MINUTES BEHIND
BUT THAT'S OKAY.
NOW WE'RE GOING TO MOVE INTO OUR
NEXT ROUND OF INVITED TALKS.
I WILL NOT SPEND LONG
INTRODUCTIONS ON THESE
INDIVIDUALS BECAUSE THEIR BIOS
ARE IN OUR PROGRAM BUT WHAT I
WILL DO IS TELL THEM YOU HAVE 15
MINUTES FOR YOUR TALK, THE LIGHT
WILL TURN YELLOW AT # MINUTES TO
GO SO BE MINDFUL SO WE CAN HAVE
5 MINUTES OF Q & A FOR YOU.
OUR FIRST SPEAKER IS DR. TORI
ELLISON.
PLEASE JOIN US.
[APPLAUSE]
>> HI, THANK YOU SO MUCH FOR
THAT INTRODUCTION.
THAT'S A GREAT TALK TO FOLLOW
RIGHT NOW.
I'M TORI ELLISON, CURRENTLY A
POSTDOC AT THE NATIONAL CENTER
FOR ADVANCING TRANSLATIONAL
SCIENCES AND TODAY I'LL BE
TALKING ABOUT THE DEVELOPMENT OF
3D BIOPRINTED INNERVATE AND
VASCULARIZED SKIN TO INVESTIGATE
PAIN PATHWAYS AND IDENTIFY
NON-ADDICTIVE PAIN MEDICATIONS.
IF YOU HAVEN'T HEARD OF THE
NATIONAL CENTER -- NCATS, WE'RE
THE YOUNGEST IC OF THE NIH.
WE'RE ONLY ABOUT 10 YEARS OLD.
AND OUR FOCUS IS ON FIGURING OUT
WAYS TO ACCELERATE RESEARCH FROM
BENCH TO BEDSIDE TO GET RESEARCH
TO PATIENTS AS QUICKLY AS
POSSIBLE.
THE MAIN WAY WE DO THIS IS
LOOKING AT THE DRUG DEVELOPMENT
PIPELINE.
IN TRADITIONAL DRUG DEVELOPMENT,
IT TAKES ABOUT 10 TO 15 YEARS
FOR A NEW DRUG TO BE APPROVED
FOR CLINICAL USE AND IT COSTS UP
TO A BILLION DOLLARS TO CREATE
ONLY ONE NEW DRUG AND USUALLY
COMPANIES WILL ONLY SEND THEIR
BEST DRUGS TO CLINICAL TRIAL,
THEY'RE THE MOST PROMMING, THE
LOWEST COST TO DEVELOP AND THE
LEAST COMPETITION ON MARKET.
BUT EVEN WITH ALL THIS MONEY,
ENERGY AND EFFORT, ONLY 12% OF
DRUGS THAT MAKE TO CLINICAL
TRIAL ARE FDA-APPROVED WHICH IS
A HUGE FAILURE RATE.
AND WHY IS THIS HAPPENING?
WE'RE PUTTING ABOUT $83 BILLION
INTO RESEARCH AND DEVELOPMENT
EVERY YEAR.
THE MAJORITY OF THAT GOING
TOWARDS ANIMAL STUDIES.
A SINGLE MOUSE CAN COST ANYWHERE
BETWEEN 100 TO $100,000 BASED ON
THE COMPLEXITY OF THE MODEL, AND
YOU'RE GOING TO NEED REPEATS.
YOU'RE NOT USING ONE MOUSE.
AND ALTHOUGH ANIMAL MODELS ARE
EXTREMELY ROBUST, THEY'RE NOT
HIGH-THROUGHPUT ASSAY SO YOU'RE
NOT GOING TO TEST A WIDE VARIETY
OF DRUGS.
YOU'RE GOING TO PICK YOUR
FAVORITES TO TETS TEST ON YOURL
MODELS THAT ARE POTENTIALLY
GOING TO MAKE TO MARKET.
A MUCH HIGHER THROUGH PUT AND
CHEAPER METHOD IS TO DO 3D
STUDIES BUT THESE CELLS ARE
ATTACHED TO A POLLLY STYRENE
PLATE THAT'S ABOUT 3 GI GA
PASCALS WHEN OUR TISSUE IS THAT
RANGE.
SO WE TEND TO SEES THEE FORCE
POLARIZED STREURKS, AND ALTHOUGH
BOTH ANIMAL MODELS AND 2D
STUDIES ARE EXTREMELY IMPORTANT
FOR DRUG DEVELOPMENT, WE'RE
SEEING THIS GAP WHERE THE DRUGS
THAT ARE MAKING TO ANIMAL MODELS
THAT ARE MAKING TO CLINICAL
TRIAL AREN'T BEING APPROVED SO
THE GOAL ISN'T TO REPLACE THESE
MODELS BUT TO BRIDGE THIS GAP
AND TO FIND A WAY TO BETTER
RECAPITULATE BODIES IN VIVO.
THE WAY WE DO THAT IN THE 3D
TISSUE IS USING 3D TISSUE
MODELS.
WE USE A WIDE VARIETY OF METHODS
TO CREATE OUR TISSUE, INCLUDING
SPHEROIDS, ORGANOIDS, TISSUE
CHIPS AND 36789D PRINTING.
3D PRINTING.
ASSAY DEVELOPMENT SPECIALISTS, I
MU KNOLL IMMUNOLOGISTS WHO OLE G
TOGETHERALL WORKTOGETHER TO CREO
OF HEALTHY AND DISEASED
ENGINEERED TISSUE MODELS.
WE FOCUS ON WHAT WE CALL THE
CONTEXT OF USE HERE.
WE'RE NOT CREATING TISSUES TO GO
INTO THE BODY.
WE'RE CREATING THESE TISSUES FOR
HIGH-THROUGHPUT SCREENS SO WE
WANT THESE TO BE CHEAP, R,
REPEATABLE AND ROBUST.
SOME OF OUR HIGH-THROUGHPUT
SCREENS WE'RE TESTING UP TO A
THOUSAND DRUGS WHICH YOU NEED A
REPEATABLE MODEL TO DO THAT.
IT ALSO IS VERY CHEAP BECAUSE WE
DON'T WANT TO END UP BEING MORE
EXPENSIVE THAN THE ANIMAL MODELS
WE'RE TRYING TO BRIDGE THE GAP
TO.
SO ONCE WE DEVELOP OUR MODELS
AND WE HAVE A HEALTHY --
DISEASE, VALIDATE THEM USING
KNOWN COMPOUNDS, WE'RE ABLE TO
APPLY THESE TO HIGH-THROUGHPUT
SCREENS.
AND IN THESE SCREENS, WE
GENERALLY TEST A LIBRARY OF
COMPOUNDS THAT WORK FOR OTHER
DISEASE, WHICH IS SOMETHING
YOU'RE NOT REALLY GOING TO SEE
IN INDUSTRY OR THE DRUG
DISCOVERY PIPELINE BECAUSE IT'S
TOO EXPENSIVE TO CROSS-TEST
COMPOUNDS.
WE'VE ALSO USED THIS FOR LEAD
OPTIMIZATION WHERE WE'RE TESTING
A NEW EXOWPPED THAT'S BEEN
DEVELOPED AT NCATS AND TESTING
DIFFERENT ITERATIONS OF IT, AND
IDEALLY WE'RE GOING TO USE THESE
MODELS TO ADVANCE THERAPEUTICS
AND MEDICAL NEEDS.
THROUGH OUR GROUP WE'VE BEEN
ABLE TO DEVELOP A WIDE VARIETY
OF MODELS THAT ARE VALIDATED
INCLUDING THE RETINA, SKIN,
LUNG, PLACENTA, CARDIAC,
NEUROVASCULAR UNIT, BRAIN,
LIVER, AND NEUROMUSCULAR
JUNCTION, AND MANY MORE.
AND MANY OF THESE WE DEVELOPED
FULLY IN HOUSE BUT ALSO THROUGH
GRANTS CALLED U GRANTS.
WE WORK WITH MANY UNIVERSITIES
WHO HAVE DEVELOPED A MODEL AND
THEY WANT TO WORK WITH US TO
FIGURE OUT HOW TO SCALE THIS OUT
FOR HIGH-THROUGHPUT ASSAYS.
BUT FOR TODAY WE'RE FOCUSING ON
PAIN.
CHRONIC PAIN AFFECTS OVER 20% OF
THE U.S. POPULATION FROM A
VARIETY OF DISEASES SUCH AS
ARTHRITIS OR ENDOMETRIOSIS, AND
THE STANDARD MEDICATION ARE
OPIOIDS.
WHICH WE ALL KNOW ARE HIGHLY
ADDICTIVE AND THE LEADING CAUSE
OF DRUG OVERDOSE.
CURRENT RESEARCH ON --
MEDICATIONS IS ACTUALLY ONE OF
THE HIGHEST INVESTMENT RATES
WHICH IS GREAT BUT WE'RE SEEING
AN EVEN HIGHER FAILURE RATE THAN
WE SEE IN GENERAL.
OVER 92% OF COMPOUNDS DEVELOPED
FOR NEURAL DISEASES RG FAILING.
WHY IS THIS HAPPENING?
IT MIGHT BE BECAUSE OUR MODELS
AREN'T PROPERLY RECAPITULATING
WHAT IS SEEN IN THE BODY.
SO IN TRADITIONAL PAIN STUDIES,
WE ASSUME THE PERIPHERAL SENSORY
NEURONS ARE THE ONLY TRANS DIERS
OF PAIN SO NEURONS ARE THE ONLY
IMPORTANT CELL, NOTHING ELSE
REALLY NEEDS TO BE MODELED.
BUT RECENT STUDIES HAVE FOUND
THE MOST IMPORTANT METHOD IS
ACTUALLY THE NEURAL EPIDURAL
PATHWAY SO THAT INTERACTION
BETWEEN NEURONS AND THE
EPIDERMIS OF OUR TISSUES.
SO WHAT WE REALLY NEED IS A 3D
MODEL TO LOOK AT THIS IN VITRO.
TO MODEL THE NEUROEPIDERMAL
JUNCTION WE DEVELOPED A 3D
PRINTED SKIN TISSUE.
SKIN IS THE LARGEST ORGAN OF THE
BODY, AND IT'S MADE UP OF A
DERMIS, EXTRACELLULAR MATRIX AND
EPIDERMIS, AND ONE THING THAT'S
RELATIVELY UNIQUE ABOUT SKIN IS
IT FORMS AN AIR-LIQUID INTERFACE
WHERE YOUR AP CAL EXPOSED
SURFACE IS EXPOSED TO AIR WHILE
WOWR BASAL SURFACE IS EXPOSED TO
LIQUID AND WE ONLY SEE THIS IN A
FEW ORGANS OF THE BODY.
TO MODEL OUR SKIN TISSUE I WAS
ABLE TO ADAPT A METHOD TO PRINT
OUR SKIN TISSUES.
WE PRINT THESE INTO A 96 -- WITH
AN 8 MY KROG PORE SIZE AND WE
AVOID EDGE WELLS.
WE'RE TRYING TO DO SOMETHING
THAT'S EXTREMELY REPEATABLE AND
TO KIND OF REMOVE HUMAN ERROR
WHEN WE'RE PRINTING TENS OF
THOUSANDS OF TISSUES, SO YOU
DON'T WANT TO INTRODUCE A
VARIATION SUCH AT EDGE EFFECTS
TO THAT.
SO FIRST WE 3D PRINT OUR
SOLUTION, IN THIS CASE MATRIGEL
IS BEING ADDED NOT FOR ITS
MECHANICAL PROPERTIES SO IT'S
BEING ADDED BELOW ITS GELATION
POINT.
NEXT I 3D PRINT A REALLY DENSE
SPHERE OF OUR NEURON SOLUTION.
THESE ARE IPSC DRIVE SENSORY
NEURONS PROVIDED AT ANOTHER
GROUP AT NCATS, THE STEM CELL
GROUP.
AND THEN WE SOAK OUR TISSUES IN
THROMBIN FOR ABOUT ONE HOUR TO
ALLOW FOR CONVERSION.
ABOUT A WEEK LATER WE HAVE
KERATINOCYTES ON TOP OF OUR
DERMIS.
AND THEN USING A 3D PRINTER MADE
BY A MEMBER -- SPACER MADE BY A
MEMBER OF OUR LAB GROUP, WE LIFT
OUR TISSUES TO AIR-LIQUID
INTERFACE WHERE THE BOTTOM AND
DERMIS OF OUR TISSUE IS TOUCHING
THE MEDIA BUT THE TOP IS EXPOSED
TO AIR SO IT'S ABLE TO STRATIFY
AND DIFFERENTIATE AND FORM OUR
FUNCTIONAL EPIDERMIS.
WE USUALLY -- DO ANY FURTHER
TESTING SUCH AS TIER, IMAGING
AND HISTOLOGY.
WHEN WE LOOK AT OUR HISTOLOGIES
HERE, WE CAN SEE WE HAVE OUR
DERMIS, AND THEN DOING I ME KNOW
HISTOCHEMISTRY AND STAINING FOR
K10 AND K14.
MATCHING A HEALTHY SKIN
PHENOTYPE FOUND IN VIVO.
SO NOT ONLY DO WE WANT NEURONAL
DEVELOPMENT BUT GOOD SKIN TISSUE
SO WE'RE USING A GOOD BASELINE.
THEN TO MAKE SURE THAT OUR
NERVES WERE FORMING WE WERE ABLE
TO STAIN THEM WITH A NEURON
SPECIFIC ANTIBODY AND OUR END
FEEL YAL CELLS SEE THE VASCULAR
NETWORKS FORMING.
WE'RE REALLY USING A LOT OF SELF
ORGANIZATION HERE, WE'RE NOT
REALLY FORCING A STRUCTURE,
WE'RE LETTING THEM DEVELOP INTO
THESE NETWORKS THEMSELVES.
SO LOYOU CAN SEE THIS 3D IMAGE T
WILL BE GOING FROM THE TOP OF
THE EPIDERMIS DOWN INTO THE
TISSUE.
SO GOING FROM THE TOP OF THE
EPIDERMIS DOWN TO THE TISSUE, WE
CAN REALLY SEE THAT OUR NERVES
HAVE INTEGRATED IN TO THE
NETWORK.
THEY'RE NOT SITTING AT THE TOP
OF THISH IT EU WHERE WE PRINTED
THEM, THEY'RE FORMING EXTENSIONS
THROUGHOUT OUR TISSUE.
AND JUST A NOTE, THIS ISN'T THE
FULL THICKNESS OF OUR SKIN
TISSUE.
OUR MICROSCOPE CAN JUST GO SO
DEEP INTO THE TISSUE BEFORE IT'S
TOO HARD TO SEE ANYTHING.
SO NOW THAT WE KNOW THAT WE ARE
FORMING EXTENSIONS WE WANT TO
MAKE SURE THEY'RE FUNCTIONAL SO
WE MEASURED SUBSTANCE P A
NEUROPEPTIDE EXPRESSED BY
NEURONS WHEN THEY'RE STRESSED
OUT SO TO STRESS OUR TISSUES OUT
WE ADD AN INFLAMMATION COCKTAIL
MADE UP OF A COUPLE DIFFERENT
CYTOKINES AND INCREASE THE
TEMPERATURE, TARGETING THE
RECEPTORS AND ION CHANNELS AND
WE NE SU MEASURED USING ELI IS D
WHAT WE FOUND IS OUR SKIN OR
SKIN WITH NERVES HAD DISTINCTLY
DIFFERENT SUBSTANCE P RELEASE,
IT'S INCREASED WHEN OUR NERVES
ARE THERE AND JUST A NOTE THIS
IS ALL NORMALIZED TO A DSO
CONTROL.
NEXT WE WANTED TO LOOK AT
ELECTROPHYSIOLOGY, WHICH IS THE
MEASURE OF ELECTRICAL RESPONSES
OF SENSORY NEURONS TO STIMULI
GENERALLY DONE USING MICRO
ELECTRODE ARRAYS WITH ELECTRODES
UNDERNEATH THE TISSUE.
OUR TRISH EUS ARE IN A TRANS
WELL PLATE SO IT'S A LITTLE MORE
COMPLICATED TO FIGURE OUT A WAY
TO SHOW ELECTROPHYSIOLOGY IN
THIS CASE.
A LOT OF MEA PLATES ALTHOUGH
EXTREMELY ROBUST ARE EXPENSIVE,
SINGLE USE AND YOU'RE REALLY
PLANNING YOUR EXPERIMENT AROUND
THAT AND KIND OF CIRCLING BACK
TO OUR CONTEXT OF USE, WE WANT
THESE TISSUES TO BE IN A WELL
PLATE METHOD WHERE WE CAN
RAPIDLY TEST DIFFERENT DRUGS.
SO WHAT WE DID TO CIRCUMVENT A
LOT OF THESE ISSUES IS WE
DEVELOPED OUR OWN CUSTOM MEA
PROBE IN-HOUSE.
THIS WAS CREATED BY A
NEUROSCIENTIST IN OUR GROUP.
SHE TOOK A MEA PROBE THAT HAS 16
TUNGSTEN ELECTRODES ON IT AND
ATTACHED TO A MANIPULATOR WITH A
CAMERA SO YOU CAN SEE WHERE THE
PROBE IS GOING INTO YOUR TISSUE.
YOU CAN MOVE WELL TO WELL
EASILY.
TO MEASURE OUR TISSUES, WE
INSERT THE ELECTRODE AND MEASURE
A BASELINE AND THEN ADD OUR
STIMULI AND RECORD THE
MEASUREMENT AND SO FOR THIS
CASE, WE USED DMSO AS CONTROL OF
OUR ISSUES, CAPSAICIN TO INDUCE
PAIN BY THE TRPV1 PATHWAY,
IL-4 TO INDUCE ITCH BY JAK1 AND
JAK3 WHICH ALSO CAUSES A LOT OF
OPIOID ADDICTION.
AND THEN WHEN WE MEASURED THESE,
YOU CAN SEE THE BASELINE OF OUR
RAW TRACE ON THE RIGHT AND
STIMULI ON THE RIGHT.
IN THE CONTROL WE DO SEE A
LITTLE BIT OF AGITATION BECAUSE
YOU'RE ADDING LI LIQUID ON TOP F
THAT EPIDERMAL GATEWAY, WHEN WE
ADD CAPSAICIN AND TRPV1 WE SEE
MUCH BIGGER SPIKES, CAPSAICIN
HAS A MUCH QUICKER EFFECT AND
THAT TRPV1 PATHWAY ABOUT FIVE
MINUTES WHILE IL4 TAKES ABOUT 30
MINUTES TO SEE A REAK SHU REACT.
WE ALSO SEE A BURST PATTERN WHEN
WE LOOK AT A RASTER PLOT.
WHAT WE SEE WHEN WE ADD
CAPSAICIN IS THEY'RE FIRING IN
SYNC, WHICH MEANS NOT ONLY DO WE
HAVE NEURITES REACHING INTO OUR
TISSUE, NOT ONLY ARE THEY
ACTIVE, BUT THEY'RE TALKING TO
EACH OTHER.
THEY'RE BURSTING IN PATTERN,
WHICH IS REALLY IMPORTANT AND
REALLY EXCITING.
SO IN CONCLUSION, WE ARE ABLE TO
BIOFABRICATE VASCULARIZED AND
INNERVATED SKIN CONSTRUCTS.
WE CAN VISUALIZE OUR NETWORKS
USING A NEURON SPECIFIC ANTIBODY
AND THEY DO SHOW PROPER SKIN
PHENOTYPE WHEN WE'RE LOOKING AT
DISEASES IN PAIN MODELING.
OUR NERVES ARE FUNCTIONAL
LOOKING AT SUBSTANCE P RELEASE
AND ELECTROPHYSIOLOGY READINGS
TO CAPSAICIN AND IL4.
WE HAVE AN ACTIVE TRPV1,
JAK1 AND JAK3 PATHWAY.
NEXT UP WE'LL BE TESTING
COMPOUNDS AGAINST THOSE PATHWAYS
TO BLOCK THEM, AND ONCE WE ARE
ABLE TO DETERMINE THAT THIS
MODEL CAN BE USED TO MODEL THE
BLOCKING OF PAIN PATHWAYS IN
VITRO, WE'LL BE ABLE TO START
TESTING NOVEL COMPOUNDS AND TO
FIND NON-PAIN MEDICATIONS THAT
STILL BLOCK THESE PAIN PATHWAYS.
AND WITH THAT, I WANT TO THANK
EVERYONE IN MY GROUP.
WE'RE EXTREMELY COLLABORATIVE,
SO MANY OF US HAVE WORKED ON
THIS.
I WANT TO THANK OUR
COLLABORATORS AT THE STEM CELL
GROUP, ANNE WHO DEVELOPED THIS
MACHINE AS WELL AS ALL OF OUR
EXTERNAL COLLABORATORS, AND
WE'RE ALWAYS LOOKING FOR MORE
EXTERNAL COLLABORATORS, LIKE ID
IS A, WE HAVE THESE U GRANTS
WHERE WHEN GROUPS DEVELOP A
REALLY COOL TISSUE OR DISEASE
MODEL, THEY CAN APLAY FO APPLY U
GRANT AND BE PAIRED WITH US,
THAT CONTEXT OF USE WHERE HOW AM
I GOING TO MOVE FORWARD AND
PRINT OR BIOFABRICATE 10,000
TISSUES FOR A STUDY.
AND THANK YOU ALL FOR BEING
HERE.
[APPLAUSE]
>> THANK YOU VERY MUCH.
THE MICROPHONES ARE IN THE ROOM,
IF PEOPLE WANT TO APPROACH THEM
WITH QUESTIONS.
PLEASE.
>> VERY, VERY INTERESTING TALK.
SO A COUPLE OF QUESTIONS.
SO WHEN YOU ADD CAPSAICIN, AND
WITH YOU WITHDRAW, DO THEY KEEP
ON FIRING OR DO THEY STOP RIGHT
AWAY?
>> WE DON'T WITHDRAW THE
CAPSAICIN, IT'S NOT ON THE PROBE
IT'S ADDED AS A LIQUID SOLUTION.
SO THEY FIRE -- I MEAN, AT A
CERTAIN POINT, IT'S GOING TO
DIFFUSE.
SO THEY FIRE FOR ABOUT 20 TO 30
MINUTES AND THEN AT A CERTAIN
POINT IT DIFFUSES AND YOU'LL SEE
A DECREASE IN THE FIRING.
>> SO THIS IS A LOCAL PAIN
MODEL, RIGHT?
>> SO IT'S A TISSUE IN A TRANS
WELL AND WE'RE ADDING THE
DILUTED STIMULI ON TOP OF THE
TISSUE.
AND SO IT'S ALL IN LIQUID.
BUT IT'S NOT, LIKE, A SINGLE
SPOT, IT'S NOT IN AN ANIMAL, SO
WE'RE NOT REALLY EVER REMOVING
THE STIMULI.
>> OKAY.
THANK YOU.
>> OF COURSE.
>> HI.
VERY INTERESTING TALK.
I MIGHT HAVE MISSED THAT PART,
BUT COULD YOU PLEASE TELL WHAT
TYPE OF HYDROGEL THAT YOU HAVE
BEEN USING FOR SUPPORTING BOTH
VASCULATURE ON NERVE CELLS?
>> YES, AND YOU KNOW, TODAY I
KIND OF WENT OVER THE BROAD
STROKES BUT IT WAS A LOT OF TIME
DEVELOPING THE RIGHT MATERIALS,
RIGHT MEDIAS, I PROBABLY TESTED
OVER 50 DIFFERENT MEDIA
FORMULATIONS TO FIND SOMETHING
THAT SUPPORTED SKIN VASCULATURE
AND NEURONS, ESPECIALLY NEURONS,
THEY'RE VERY PICKY, BUT WE USE A
RELATIVELY SIMPLE GEL
FORMULATION WITH GELS IN IF I
BRIN AND MAY TRI GEL TO FORM OUR
DERMIS.
MY BACKGROUND IS MATERIALS
ENGINEERING.
I DON'T ALWAYS LOVE USING MAY
TRI GEL SINCE IT IS KIND OF A
MYSTERY BOX BUT THE NEURONS LOVE
IT.
THE OTHER TISSUES ARE HAPPY WITH
COLLAGEN INSTEAD, THE NEURONS
LOVE IT, AND I DO AT LAMINEN TO
OUR NEURONS HERE.
BUT IT'S REALLY JUST A GELATIN
AND FIBRIN BASE, IT'S A VERY
SIMPLE HYDROGEL.
>> WE'LL TAKE OUR LAST QUESTION
BEHIND YOU.
>> VERY INTERESTING TALK.
I WAS CURIOUS WHEN YOU SHOWED
THE COMPARISON BETWEEN YOUR
INNERVATED SKIN MODEL AND SKIN.
IS THAT AGAINST NATIVE HUMAN
SKIN OR --
>> NO, THAT'S BETWEEN OUR THREE
PRINTED SKIN.
WE HAVEN'T TESTED NATIVE YET,
THAT WOULD BE A GOOD KIND OF
COMPARISON, THIS IS COMPARING TO
OUR SKIN WITHOUT NERVES TO SKIN
WITH NERVE SO WE SEE AN INCREASE
IN SUBSTANCE P RELEASE.
>> THE STIMULI THAT YOU USE TO
LOOK AT DIFFERENT RESPONSES, IS
THAT PHYSICIAN LONG CAL -- SAME
LEVEL AT PHYSIOLOGICAL STIMULI
OR IS THAT SUPER PHYSIOLOGICAL?
>> I GUESS ARE YOU TALKING THE
AMOUNTS OF CAPSAICIN AND IL4?
I KIND OF BASE IT OFF WHAT
PEOPLE DO IN RAT MODELS BECAUSE
THAT'S WHERE WE MOSTLY SEE
CAPSAICIN STUDIES, BUT I BASE
THE CONCENTRATION ON THE AMOUNT
OF LIQUID VOLUME WE HAVE WITH
OUR TISSUES TO KIND OF ADAPT IT.
SO I THINK THE CAPSAICIN IS LIKE
10 MIC MICROMOLAR SO IT'S PRETTY
LOW.
>> COOL.
THANK YOU.
>> LET'S THANK OUR SPEAKER,
PLEASE.
[APPLAUSE]
OKAY, THANK YOU.
THAT WAS REALLY NICE.
SO OUR NEXT SPEAKER IS
DR. HANJOONG JO, EMORY
UNIVERSITY.
>> THANK YOU, MANU.
THIS IS ESPECIALLY AN
EXCEPTIONAL HONOR TO SPEAK IN A
CONFERENCE WHERE MY MOST ESTE
ESTEEMED COLLEAGUE AND MY FORMER
STUDENT ORGANIZED.
SO THANK YOU SO MUCH.
SO I WANT TO TALK ABOUT HOW
ENDOTHELIAL CELLS ARE
REPROGRAMMED BY DISTURBED FLOW
AND HOW THIS CAN CAUSE@THROW
SCLEROSIS.
I WANT TO BRING THE CONCEPT OF
MOVING FROM MECHANOBIOLOGY TO
MECHANOMEDICINE.
SO@THROW SCLEROTIC DISEASE IS A
LEADING CAUSE OF DEATH, SUCH AS
HEART ATTACK, ISCHEMIC STROKE
AND PERIPHERAL ARTERY DISEASE
CONTINUES TO BE A LEADING CAUSE
OF DEATH WORLDWIDE.
THIS IS DESPITE THE FACT THERE
ARE A LOT OF GREAT DRUGS SUCH AS
STATINS THAT CAN LOWER ONE OF
THE IMPORTANT RISK FACTORS SUCH
AS HIGH CHOLESTEROL.
WHAT THIS TELLS YOU IS BRINGING
DOWN HIGH CHOLESTEROL ENOUGH IS
NOT ENOUGH AND WE NEED A NEW
ADDITIONAL DRUG THAT TARGETS
NON-LIPIDS, AND THIS IS WHERE WE
HAVE BEEN REALLY FOCUSING ON
FLUID DEPENDENT CHANGES IN
ENDOTHELIAL CELLS AS A SOURCE OF
NEW TARGETED THERAPEUTICS.
IT OCCURS IN PLACES OF BRANCHING
POINTS SUCH AS HERE, FLOW IS
REALLY CIRCULATING HERE AND THIS
IS EXPOSED IN THE OUTER PORTION
OF THIS CAROTID BRANCH TO A LOW
AND OSCILLATING -- THIS IS WHAT
WE CALL A DISTURBED FLOW.
THIS IS WHERE ATHEROSCLEROSIS IS
TYPICALLY FOUND, BUT WHAT WAS
UNKNOWN WAS BL THIS DISTURBED
FLOW CAN ACTUALLY CAUSE THE
DISEASE.
SO WE DEVELOPED AN ANIMAL MODEL
ABOUT -- IN 2009, THIS IS CALLED
A MOUSE CAROTID LIGATION MODEL
OF ATHEROSCLEROSIS.
IN THIS MODEL, WE'RE USING ONE
OF THE TWO CAROTID ARTERIES IN
THE NECK, SO YOU ALL HAVE THIS
STRAIGHT PORTION OF THE NECK,
THE CAROTID ARTERY THAT I
EXPOSED TO A STABLE FLOW, BUT IF
WE CHANGE FLOW CONDITIONS BY
JUST LIGATING THREE OF THE FOUR
SMALL BRANCHES DOWNSTREAM, WE
CAN CHANGE PATTERN FROM ONE SIDE
OF THE CAROTID ARTERY TO A
STABLE UNIDIRECTIONAL HIGH
STRESS TO LOW OSCILLATING STRESS
TYPE THAT YOU TYPICALLY FOUND IN
PRO ATROAGENIC REGIONS.
SO IF WE DID THIS SURGERY IN
HIGH KLOSS TROLL MICE SUCH AS
APOE MICE, THE LEFT PORTION OF
THE CAROTID ARTERY THAT ARE
EXPOSED TO DISTURBED FLOW
DEVELOPS ATHEROSCLEROSIS WITHIN
TWO WEEKS, WHILE IN THE SAME
ANIMAL, THE RIGHT SIDE, WHICH IS
USED AS A CONTROL, EXPOSED TO
STABLE FLOW CONDITIONS, IS
PROTECTED FROM ATHEROSCLEROSIS,
DESPITE THE FACT THAT
CHOLESTEROL LEVEL IS NEARLY
1,000 MILLIGRAMS PER DECILITER.
YOU CAN ACTUALLY SEE HERE IN A
CROSS-SECTION, IN A
TIME-DEPENDENT MANNER THAT BY
TWO WEEKS, YOU CAN SEE
ATHEROSCLEROSIS AND IT INCREASES
FURTHER IN A TIME-DEPENDENT
MANNER, BUT IN THE RIGHT SIDE,
THEY REMAIN PLAQUE-FREE.
SO WE AND OTHERS NOW HAVE USED
THIS MOUSE MODEL TO UNDERSTAND
HOW DISTURBED FLOW ACTUALLY
CAUSES ATHEROSKLARE OW SKLARE OE
ATHEROSCLEROSIS SOSUDDENLY.
THIS IS MEDIATED THROUGH A AN
OMICS CHANGE, GENOME WIDE, EP
GINO WIDE AND METABOLOMICS WIDE
CHANGES OCCURRING IN ENDOTHELIAL
CELLS IN RESPONSE TO FLOW AND
THIS THEN CAUSES GRADUAL CHANGES
IN ENDOTHELIAL DYSFUNCTION,
ATRIAL FORMATION AND AT THE SAME
TIME STIMULATING IMMUNE
INFILTRATION INTO THIS AREA,
THEREBY PLAQUE OCCURS.
SO TW TO REALLY UNDERSTAND THE
SPECIFIC MORE DETAILED
MECHANISMS BY WHICH FLOW
REGULATES THESE RAPID
ATHEROSCLEROSIS DEVELOPMENT, WE
HAVE DONE A LOT OF DIFFERENT
OMIC STUDIES USING OUR PARTIAL
LIGATION MODEL, SOMETHING I WILL
DISCUSS A LITTLE BIT MORE.
SO THROUGH MANY OF THESE OMIC
STUDIES AND LOOKING AT SINGLE
CELL RNA SEQUENCING, BULK RNA
SEQUENCING, MICRORNAs, AND DNA
METHYLOME STUDIES AND
METABOLOMICS STUDIES BE WE HAVE
IDENTIFIED NUMEROUS DATA,
NUMEROUS GENES AND METABOLIZED
THE CHANGE IN RESPONSE TO FLOW
DISTURBANCE, AND THEN THEY HAVE
BEEN NOW ANALYZED THROUGH
VARIOUS TECHNIQUES INCLUDING
MACHINE LEARNING AND WE ARE ALSO
TRYING TO USE A.I. FOR THE
ANALYSIS BASED ON THIS, WE
IDENTIFIED A LOT OF GENES, AND
WE HAVE STUDIES SPECIFIC
MECHANISMS IN CELLULAR MODELS AS
WELL AS INVO IN VIVO MODELS AND
ON THESE STUDIES WE HAVE
IDENTIFIED MANY THERAPEUTIC
TARGETS AND SOME OF THEM ARE
LISTED HERE, INCLUDING HEG1 THAT
WE RECENTLY PUBLISHED, AND ONCE
WE HAVE IDENTIFIED THESE GENES,
THEN WE ALSO DEVELOPED A
TARGETED THERAPEUTICS METHOD
SUCH AS A LIPID NANOPARTICLE OR
ULTRASOUND-TARGETED
METHODOLOGIES, AND WHEN WE WERE
SUCCESSFUL BY TARGETING EVEN ONE
GENE, ONE FLOW SENSITIVE GENE,
WE COULD ACTUALLY SHOW THAT WE
CAN REVERSE FLOW ATHEROSCLEROSIS
IN THIS MODEL TO ALMOST NORMAL
CONDITIONS.
WHAT THIS DEMONSTRATED WAS THAT
IF WE CHOOSE THE RIGHT
MECHANOSENSITIVE GENES AND
TARGET THEM, WE CAN ACTUALLY
PREVENT ATHEROSCLEROSIS AND
REVERSE ATHEROSCLEROSIS.
SO TO DISCUSS THIS IN MORE
DETAIL, WHAT WE DID WAS WE USED
SINGLE CELL CELL SCREENING USIR
LIGATION MODEL.
IN THIS CASE WE WANTED TO SEE
WHAT IS THE EFFECT OF DISTURBED
FLOW ALONE WITHOUT USING
HYPERCHOLESTEROL EMIA AND AFTER
TWO DAYS AND TWO WEEKS FOLLOWING
PARTIAL FERTILIZATION WE THEN
DID SINGLE CELL RNA SEQUENCING.
INITIALLY WHAT WE FOUND WAS IF
YOU LOOK AT SINGLE CELL RNA
SEQUENCING IN THIS U MAP
ANALYSIS THIS TOTAL DATA IS NOW
DIVIDED INTO TWO DAYS AND TWO
WEEKS.
SO RCA IS THE CONTROL SIDE, AND
LCA IS THE SIDE WHERE THEY WERE
EXPOSED TO DISTURBED FLOW
CONDITIONS.
AND IN THE RIGHT SIDE, WHERE
THEY WERE EXPOSED TO STABLE
FLOW, YOU CAN SEE WE HAVE FOUR
DIFFERENT TYPES OF ENDOTHELIAL
CELLS, BUT THESE ACTUALLY CHANGE
IN RESPONSE TO FLOW AND AFTER
TWO WEEKS, WE CAN ACTUALLY SEE A
NEW TYPE OF ENDOTHELIAL CELLS
EMERGING SUCH AS EA TYPE HERE,
COMPARED TO A PROTOTYPICAL E2 --
TYPES.
WHAT THEY ACTUALLY SHOW THAT --
HEALTHY TYPE, ONE GOES TOWARD A
MESENCHYMAL TYPE, AND WE ALSO
IDENTIFIED A NEW TYPE OF
TRANSITION WHICH WAS ENDOTHELIAL
CELLS MOVING TOWARD ENDOTHELIAL
SIDE.
NOW THEY DIDN'T MOVE ALL THE WAY
TO THESE IMMUNE CELL TYPES SO WE
CALLED THEM PARTIAL IND THEEL
YAL CELL TO IMMUNE CELL
TRANSITION, AND THIS OCCURS JUST
IN RESPONSE TO DISTURBED FLOW
ALONE.
SO WE CAN ALSO SHOW THAT IF WE
JUST USE A -- EXPOSE THEM TO
EITHER A STABLE FLOW CONDITIONS
OR DISTURBED FLOW CONDITIONS IN
AN IN VITRO SETTING, WE CAN
INDUCE IMMUNE CELL CHANGE AS
WELL AS MESENCHYMAL CHANGE IN AN
IN VITRO SETTING JUST USING
ENDOTHELIAL CELLS ALONE, AGAIN
DEMONSTRATING IN RESPONSE TO
FLOW, ENDOTHELIAL CELLS
TRANSITION TO ME MESENCHYMAL AND
IMMUNE CELL TYPES.
SO BASED ON THIS CONCEPT, WHAT
WE PROPOSED WAS THAT DISTURBED
FLOW ALONE CAN CHANGE EP GENOMIC
AND TRANSCRIPTOMIC-WIDE CHANGES
THAT LEAD TO ENDOTHELIAL CELL
INFLAMMATION, ENDOTHELIAL CELL
TO MESENCHYMAL TRANSITION AND
PARTIAL ENDOTHELIAL CELL TO
IMMUNE CELL TRANSITION.
AND WE COINED THE TERM BASED ON
THIS, A FLOW INDUCED
REPROGRAMMING OF ENDOTHELIAL
CELLS OR PARTIAL FIRE.
WE THOUGHT THAT THIS PARTIAL
FIRE MAY BE RESPONSIBLE FOR
ATHEROSCLEROSIS.
SO, SO FAR I DESCRIBED AN
EXPERIMENT WHERE WE JUST USED
DISTURBED FLOW CONDITIONS.
HOW ABOUT IF WE COMBINE DISTAL
FLOW WITH HYPERCHOLESTEROL EMIA?
BECAUSE AS YOU WILL SEE HERE,
DISTURBED FLOW ALONE DOES NOT
CAUSE ATHEROSCLEROSIS.
TO CAUSE IT, WE NEED TO COMBINE
DISTURBED FLOW WITH
HYPERCHOLESTEROL EMIA.
SO WE HAD FOUR DIFFERENT
CONDITIONS HERE, A CONTROLLED
CONDITION, DISTURBED FLOW ALONE,
AND HIGH CHOLESTEROL ALONE, AND
DISTAL FLOW, PLUS
HYPERCHOLESTEROL EMIA.
UNDER THESE CONDITIONS, AFTER
FOUR WEEKS OR TWO WEEKS, WE THEN
DID A SINGLE CELL RNA
SEQUENCING.
AND WHAT WE FOUND WAS THAT WE
FOUND ABOUT 26 DIFFERENT TYPES
OF CELLS FROM OUR SINGLE CELL
DATA REPRESENTING ALL THE CELLS
THAT YOU EXPECT TO SEE FROM A --
THAT INCLUDES FIVE DIFFERENT
TYPES OF ENDOTHELIAL CELLS,
THREE DIFFERENT TYPES OF SMOOTH
MUSCLE CELLS AND AGAIN MANY T
CELLS, DENDRITIC CELLS,
MACROPHAGES, AS WELL AS GUY PRO
SWOALS FIBROBLASTSAND NEUTROPHI.
WE THEN LOOKED AT IN A LITTLE
BIT MORE DETAIL IN A DIFFERENT
CONDITION.
WE HAVE ACTUALLY 10 DIFFERENT
CONDITIONS, SO THREE DIFFERENT
CONTROL CONDITIONS, HIGH
CHOLESTEROL ALONE, AND DISTAL
FLOW ALONE, AND DISTAL FLOW
UNDER HIGH CHOLESTEROL
CONDITIONS.
YOU CAN SEE WE HAVE ABOUT FIVE
DIFFERENT TYPES OF ENDOTHELIAL
CELLS.
IT STARTS WITH A HEALTHY
ATHEROPROTECTIVE ENDOTHELIAL
CELLS TO SMOOTH MUSCLE
CELL-LIKE, AND ANOTHER TYPE IS
PRO-INFLAMMATORY AND ANGIOGENIC
TYPE, AND THE OTHER IS ALSO
ANOTHER ENDMT TYPE, AND ONE
OTHER TYPE THAT WE SAW WAS A
ENDOTHELIAL CELL BECOMING IMMUNE
CELLS.
ALSO IT ALSO BECOMES A -- FORM
CELLS, SO WE ACTUALLY CALLED IT
AN ENDO FT AS WELL.
THERE IS NOT MUCH CHANGE -- TO
OUR SURPRISE, HIGH CHOLESTEROL
ALONE IN VIVO DIDN'T DO MUCH ON
ENDOTHELIAL CELL TRANSCRIPTOMIC
CHANGE, BUT IF YOU SUBJECT THEM
TO DISTURBED FLOW, YOU CAN SEE
THE COLOR CHANGES, THAT MEANS
ENDOTHELIAL CELLS SHOWING
DIFFERENT TRANSCRIPTOMIC
PROFILES AND THEY BECOME REALLY
RED, THAT MEANS ENDOTHELIAL
CELLS ARE REALLY TRANSFORMING TO
IMMUNE CELLS AND -- TYPES.
THESE ARE ALL THE DETAILED
MARKERS WE USED HOW TO DESIGNATE
WHETHER THEY ARE HEALTHY CELLS,
INFLAMED, PRO ANGIOGENIC, AR
FORM SEROTYPES.
NOW COMBINING ALL THE DATA
TOGETHER AGAIN, WE CAN SEE THAT
THEY ARE EXPOSED TO HIGH
CHOLESTEROL CONDITIONS.
THERE ARE NOT MUCH CHANGES IN
THE CELL TYPES BUT AS SOON AS
YOU PUT THEM UNDER DISTURBED
FLOW CONDITIONS, THEY CHANGE.
THIS OSTRICH-LOOKING SHAPE HAS
BEEN DISINTEGRATED BY -- AND BY
COMBINING DISTURBED FLOW WITH
HIGH -- YOU CAN -- THAT'S WHAT
CHANGES BY A DISTAL FLOW ON THE
HYPOCHOLESTEROL I'M WHAT.
WE HAVE DONE A LOT OF DETAILED
VALIDATION, SO WE USED A
CONFETTI MICE TO DO FATE MAPPING
STUDIES.
WE CAN SEE CONFETTI -- YOU CAN
JUST FOCUS ON RED CELLS, SO RED
CELLS ARE GENETICALLY CODED
ENDOTHELIAL CELLS, AND THEY
EXPRESS MARKERS OF INFLAMMATION
SUCH AS VCAM1 AS WELL AS ICAM1.
AND TO SEE WHETHER THEY ARE
UNDERGOING ENDO MT, WE CAN
AAGAIN FOCUS ON THE CONFETTI
MARKERS, RED AND WHITE STAINING
SHOWING THE MARKETERS -- AND
CNN1 ARE EXPRESSED.
AGAIN IMMUNE CELL MARKER, CD68,
C1QA, C1QB, AND LYZ2, THESE ARE
ALL IMMUNE CELL MARKERS, SO
AGAIN JUST DEMONSTRATING THAT
ENDO IT OCCURS.
FINALLY ENDOTHELIAL -- SO SPP1,
LG AL3, TREM2 AND BODIPY, THESE
DEMONSTRATE ENDOTHELIAL CELLS
INDEED BECOME -- CELLS.
SO IN SUMMARY, WHAT WE HAVE
SHOWN IN THIS STUDY WAS A
TWO-HIT HYPOTHESIS.
WHAT HAPPENS IS THAT HALF THE
END FEEL YELL CELLS IN RESPONSE
TO DISTURBED FLOW ALONE, THEY
TRANSITION TOWARD THE -- THEY
BECOME INFLAMED AND THEY BECOME
TO ATTRACT IMMUNE CELLS SUCH AS
MONOCYTES, THEN WITH ONCE YOU T
THEM INTO HYPERCHOLESTEROL
CONDITIONS ON TOP OF DISTURBED
FLOW THEN THE ENDOTHELIAL CELLS
UNDERGO LEADING TO PLAQUE
DEVELOPMENT.
SO AGAIN, THIS FLOW ALONE IS NOT
ENOUGH, HYPERCHOLESTEROL EMIA IS
NOT ENOUGH TO CAUSE
ATHEROSCLEROSIS, YOU NEED BOTH
CONDITIONS AND BY TARGETING
FLOW-SENSITIVE GENES WHICH
ACTUALLY CAUSES THE INITIAL
FIRE, AND NOW ONCE YOU HAVE THIS
PILOT LIGHT ON AND IF YOU THROW
IN FUEL WHICH IS HIGH
CHOLESTEROL IS REALLY THE FUEL,
THEN IT CATCHES THE FULL FIRE
THAT LEADS TO ATHEROSCLEROSIS.
BY FOCUSING ON THIS TARGET FLOW
SENSITIVE GENES, I THINK WE
COULD DEVELOP A NEW THERAPEUTIC
TARGET.
SO I WANT TO ACKNOWLEDGE MY TEAM
AND ALSO THE FUNDING FROM NIH.
THANK YOU VERY MUCH FOR YOUR
ATTENTION.
[APPLAUSE]
>> THAT IS GREAT.
IF YOU HAVE QUESTIONS, CAN WE
MOVE TO THE MICROPHONES?
>> HOW DOES THE FLOW GET TRANS
DAWESED TO ACTIVATE THE GENES?
>> THERE ARE DOZENS OF
MECHANOSENSORS ON TOP OF
ENDOTHELIAL CELLS AS WELL AS
CELL-CELL JUNCTION AS WELL AS
INAT THE GRIN AND -- THESE ARE
ALL MECHANOSENSORS THAT DIRECTLY
SENSES -- AND THEN THEY
TRANSDUCE THE SIGNALS INSIDE.
>> INSIDE TO THE NUCLEUS?
>> YES, IT GOES ALL THE WAY TO
NUCLEUS.
SO THERE IS SOME DIRECT WIRING
FROM THE MEMBRANE TO NUCLEUS AS
WELL PLUS THERE ARE ADDITIONAL
CELL SIGNALING PATHWAYS THAT ARE
TURNED ON.
>> I'VE SEEN SOME OF THIS DATA
BEFORE SO THANK YOU FOR SHARING
IT.
WE TALKED -- YOU STILL HAD
MONOCYTES COMING INTO THAT WALL.
IF YOU DID THIS IN A MOUSE MODEL
DEPLETED OF MONOCYTES, DO YOU
YOU THINK THE PLAQUES WOULD BE
AS AGGRESSIVE OR DO YOU THINK
MONOCYTES AND A -- WOULD BE A
THIRD --
>> MONOCYTE AND MACROPHAGE IS AN
ESSENTIAL INCREED YEN INGREDIENM
CELLS.
SO THE PLAQUE PROBABLY WOULD NOT
OCCUR TO ANY DEGREE.
>> AND WITH THE ENDO IT
TRANSITION, WOULD -- AGAIN, JUST
WHAT YOU THINK WOULD HAPPEN,
WOULD YOU GET MORE ENDOTHELIAL
FOAM CELLS IF THEY DON'T HAVE
THE MONOCYTE DERIVED CELLS?
>> THAT'S A GOOD QUESTION.
IELG HAVE TO ACTUALLY DO THE
EXPERIMENT.
BUT THERE WILL BE SOME
CONTRIBUTION FROM ENDOTHELIAL
CELLS ACTUALLY ABOUT 11% OF --
CELLS ARE DERIVED FROM
ENDOTHELIAL CELLS, ABOUT 30% OF
THEM ARE SMOOTH MUSCLE CELL
DERIVED, THE OTHER ARE
MACROPHAGE DREE RIFED.
SO THE PLAQUE WE SEE IN THE
PLAQUE IS COMBINATION OF AT
LEAST THREE DIFFERENT CELL
TYPES.
>> ONE FINAL QUESTION, THIS WILL
BE THE FINAL QUESTION, I GUESS.
WE THINK THEIR NATIVE FUNCTION
IS TAKING LDLs FROM THE BLOOD
AND PASSING IT THROUGH TO THE
WALL, BUT THEY ARE NOW RETAINING
THAT LIPID IN THE INTEREST OF
ANOTHER -- ANY OF THE GENES
YOU'VE SEEN IN YOUR SINGLE CELL,
ARE THERE TRANS -- PATHWAYS THAT
ARE BEING DISRUPTED IN THAT
ENDOLE TO IT TRANSITION?
>> YES, ACTUALLY IN THAT AREA,
ONE OF THE FIRST THINGS THAT
CHANGE IS THE -- CHANGE, SO LDL
PERMEABILITY, FOR EXAMPLE, GOES
UP, AND SOME OF THE ENDOTHELIAL
CELLS THAT BECOMES IMMUNE CELLS
OR FORM CELL TYPES, THEY ALSO
MIGRATE INSIDE TOWARD THE PLAQUE
AS WELL.
SO A LOT OF THINGS ARE GOING ON.
>> ALL RIGHT.
LET'S THANK OUR SPEAKER.
THANK YOU VERY MUCH.
EXCELLENT MENTOR.
[APPLAUSE]
ALL RIGHT AND THE FINAL SPEAKER
OF THE AFTERNOON SESSION IS
JOINING US ALSO FROM NOT THE NIH
BUT FROM GOVERNMENT HOSPITAL
UNIVERSITY SYSTEMS HOSPITAL AND
I WILL JUST TURN THIS OVER TO --
WHAT'S HER NAME?
CATE WISDOM.
THANK YOU.
SORRY.
>> THANK YOU SO MUCHMENT MY NAME
IS CATE WISDOM AND I'M AT THE
UNIFORMED SERVICES UNIVERSITY IN
THE 40 BIOCUBE CENTER FOR
BIOTECHNOLOGY.
AND I'M VERY EXCITED TODAY TO BE
HERE AND TO SHARE WITH YOU SOME
OF THE WORK THAT'S BEEN DONE AS
PART OF THE LARGER FAME PROGRAM
THAT'S ACTIVE IN OUR 16 TE AND
FAME STANDS FOR FABRICATION IN
AUSTERE MILITARY ENVIRONMENTS.
A DISCLAIMER, THESE VIEWS ARE MY
OWN AND DO NOT REFLECT THE VIEWS
OF THE UNIFORMED SERVICES
UNIVERSITY OR THE DEPARTMENT OF
DEFENSE.
FIRST I WANT TO START BY
ESTABLISHING KIND OF THE
CHALLENGE.
SO MEDICAL RESPONSE TO MILITARY
CONFLICTS, NATURAL DISASTERS AND
HUMANITARIAN CRISES ARE VERY
COMPLICATED.
THEY CAN BE COMPLICATED BY
OPERATIONAL LOGISTICS THAT HAVE
UNRELIABLE SUPPLY CHAINS, EITHER
FROM ADVERSARIAL ATTACK OR JUST
INFRASTRUCTURE THAT'S BEEN
DESTROYED.
THINGS LIKE RHODES, BRIDGES AND
AIRPORTS THAT MIGHT HAVE BEEN
DESTROYED BY A NATURAL DISASTER.
THERE'S ALSO DELAYED MEDICAL
EVACUATION, THIS IS GOING TO
REQUIRE MORE MEDICAL EQUIPMENT
AND CONSUMABLES IN ORDER TO CARE
FOR THESE PATIENT.
S.
ADDITIONALLY, WHEN RESPONDING
THERE COULD BE DIFFERENT SERVICE
BRANCHES, NATIONS, NGOs OR
HUMANITARIAN AID ORGANIZATIONS
THAT RESPOND.
AND THE MEDICAL EQUIPMENT AND
CONSUMABLES THAT THEY BRING ARE
NOT GUARANTEED TO BE COMPATIBLE
WITH ONE ANOTHER.
ADDITIONALLY, STOCKS OF MEDICAL
SUPPLIES CAN BE QUICKLY
DEPLETED, AND THERE COULD
POTENTIALLY BE A HIGHER
LIKELIHOOD OF FAILURE OF MEDICAL
DEVICES JUST FROM OVERUSE.
NEXT I WANT TO TALK ABOUT HOW
THE MILITARY OPERATIONAL UNIT
RECEIVES MEDICAL MATERIAL.
SO THE OPERATIONAL UNIT WILL
PLACE AN ORDER WITH THE MILITARY
TREATMENT FACILITY.
THE MILITARY TREATMENT FACILITY
THEN PLACES AN ORDER WITH THE
PRIME VENDOR.
THE PRIME VENDOR FULFILLS THE --
WHICH THEN DISTRIBUTES TO THE
OPERATIONAL UNIT.
NOW THE MILITARY TREATMENT
FACILITY HAS TO PREDICT THE
NUMBER OF ITEMS THAT THEY
ANTICIPATE NEEDING OUT TO 30
DAYS IN ADVANCE AND IF THEY
PREDICT CORRECTLY THEN THE PRIME
VENDOR HAS A STANDARD 7 DAY
DELIVERY WINDOW.
HOWEVER, IF THE ORDERED ITEMS'
QUANTITY EXCEEDS WHAT WAS ECK
INSPECTED THEN THE PRIME VENDOR
HAS UP TO 37 DAYS TO FULFILL
THAT ORDER.
AND IF AN INFREQUENTLY ORDERED
ITEMS IS REQUESTED THEN THE
PRIME VENDOR HAS UP TO 90 DAYS
TO FULFILL THAT ORDER.
THIS VO SUMS UP THE PROBLEM: IT
TAKES THREE MONTHS TO GET A PART
THAT COSTS $30 TO FIX A
$3 MILLION PIECE OF EQUIPMENT.
WE BELIEVE THAT ONE POTENTIAL
SOLUTION CAN BE ADDITIVE
MANUFACTURING AT OR NEAR THE
POINT OF NEED.
THIS CAN INCLUDE 3D PRINTING AND
3D SCANNING WITH BIOMINUTING
CAPABILITIES AS THE AT OR NEAR
THE POINT OF NEED.
WE ENVISION THIS BEING A COMMON
PARTS DATABASE THAT CAN BE --
AND THE CLOUD OPTION ENABLES
REMOTE DESIGN AND ENGINEERING
SUPPORT, OR WE CAN USE 3D
SCANNERS TO POINT OF NEED
GENERATE PRINT FILES AND
DIGITALLY REPAIR PARTS.
TAKEN TOGETHER, THIS COULD BE A
POTENTIAL SOLUTION TO THE
CHALLENGES OF CONTESTED
LOGISTICS ENVIRONMENTS.
DURING THE FAME PROGRAM, WE'VE
DEMONSTRATED ADDITIVE
MANUFACTURING IN THREE DIFFERENT
MISSION DOMAINS.
THE FIRST MISSION DOMAIN WAS A
DESERT ENVIRONMENT IN WHICH WE
DEPLOYED A THERMAL PLASTIC
PRINTER AND BIOPRINTING
CAPABILITIES.
THE SECOND MISSION DOMAIN WAS
ABOARD THE INTERNATIONAL SPACE
STATION IN WHICH WE INVESTIGATED
BIOPRINTING.
AND THE THIRD MISSION DOMAIN WAS
IN AN ARCTIC ENVIRONMENT, IN
WHICH WE DEPLOYED A AUSTERE -- A
COMMERCIALLY AVAILABLE 3D
PRINTER WITH THERMOPLASTIC
PRINTING CAPABILITIES AND 3D
SCANNING TECHNOLOGY.
FOR THE REST OF MY TALK, I'M
GOING TO FOCUS ON THE AUSTERE
ENVIRONMENT.
HOWEVER, THE REFERENCES TO THE
OTHER TWO ENVIRONMENTS AND THE
WORK THAT WAS COMPLETED THERE
ARE LISTED HERE FOR YOU TO
REVIEW.
FIRST BEFORE WE COULD DO ANY
PRINTING WE HAD TO FIGURE OUT
HOW TO GET OUR EQUIPMENT TO THE
AUSTERE ARCTIC LOCATION.
TO DO THIS, WE INVESTIGATED TWO
DIFFERENT SCHEMES.
THE FIRST SCHEME WAS ACTUALLY TO
PACKAGE THE COMMERCIAL PRINTER
IN THE MANUFACTURE PACKAGING,
PLACE IT IN A CANVAS ZIPPER BAG
WITH WHEELS, AND CHECK IT AS
CHECKED BAGGAGE ON A COMMERCIAL
AIRLINE CARRIER.
IN ADDITION TO THE 3D PRINTER,
WE TOOK AN AIR HANDLER, EXTRA --
3D SCANNER AND OTHER MATERIALS
WITHIN A PELICAN CASE AND TWO
LARGE SUITCASES.
THE ADVANTAGE OF THIS SCHEME IS
THAT THE MATERIALS ARRIVE WITH
THE PERSONNEL.
BUT THERE ARE SOME ADDITIONAL
CHALLENGES TO CONSIDER.
SUCH AS THE SIZE OF RURAL AIR
AND GROUND TRANSPORTATION IS NOT
UNIVERSAL.
YOU ALSO NEED TO CONSIDER
INTERNATIONAL WEIGHT AND SIZE
CONSIDERATIONS WHICH CAN VARY
AMONGST AIRLINES AND CAN BE
DIFFERENT THAN DOMESTIC
AIRLINES.
YOU ALSO NEED TO CONSIDER
CUSTOMER REQUIREMENTS.
AND WHAT TYPES OF MATERIALS AND
EQUIPMENT ARE GOING TO BE
ALLOWED IN TO THE COUNTRY THAT
YOU'RE TRYING TO DEPLOY THEM
INTO.
THE SECOND SCHEME WE EVALUATED
WAS TO SHIP THE RUGGEDIZED
PRINTER ON A PALLET USING A
COMMERCIAL SHIPPING CARRIER.
FOR THIS SCHEME, WE HAD
ANTICIPATED RECEIVING THE PALLET
AT SEVEN DAYS.
HOWEVER, THERE WAS A DELAY IN
THE CUSTOMS PROCESS THAT WE
WEREN'T ABLE TO BEGIN TESTING
UNTIL DAY 14.
SO THIS IS SOMETHING THAT NEEDS
TO BE CONSIDERED WHEN TRYING TO
ADDRESS SOME OF THE CHALLENGING
LOGISTICS SCHEMES.
ONCE THE PRINTERS ARRIVED, WE
DEMONSTRATED THAT WE COULD PRINT
PARTS FROM A COMMON PART
DATABASE.
WE PRINTED FROM MATERIALS LIKE
POLL' CARBONATE, POLYCARBONATE
HAVING THE ADVANTAGE IT CAN BE
AUTOCLAVE STERILIZED.
ADDITIONALLY WE PRINTED PARTS
LIKE FACE SHIELDS, EYEGLASS
FRAMES, BARBED TUBING ADAPTORS
MAYBE TO PROMOTE SOME
COMPATIBILITY BETWEEN THOSE
DESPERATE SUPPLIES.
WE ALSO MADE I VBAC HOLDERS,
CLAMPS, HANDLES, A MEDICAL
DEVICE HOUSING, AND A SNOWMOBILE
SWITCH.
THIS SNOWMOBILE SWITCH WAS
ACTUALLY AN UNUSED CASE, THE
PARTNER CAME AND ASKED IF WE
COULD PRINT A 37D REPLACEMENT
KNOB.
THESE KNOBS TYPICALLY COST THEM
$900 TO REPLACE BECAUSE THEY
HAVE TO PURCHASE THE ENTIRE
HOUSING BUT THEY JUST NEED THE
KNOB.
ADDITIONALLY THEY'RE SUBJECT TO
THE SUPPLY CHAIN ISSUES AND
ACCESS TO THIS AUSTERE ARCTIC
LOCATION.
WITHIN 15 MINUTES, WE LOCATED
THE PART INTO THE 3D PRINTER
SOFTWARE, IT GENERATED A PRINT
FILE WITH WATER, DISSOLVABLE
SUPPORT MATERIAL, AND IN THREE
HOURS AND 45 MINUTES, WE
MANUFACTURE A REPLACEMENT KNOB
OUT OF NYLON CARBON FIBER.
SO IN A TOTAL OF SIX HOURS, WE
WERE ABLE TO GENERATE A PART
FILE AND A REPLACEMENT PART AND
WE WERE ABLE TO DO THIS FOR
$3.23.
NEXT WE EVALUATED BIOPRINTING IN
THE AUSTERE ARCTIC LOCALE, AB TO
DO THIS, WE LOOKED AT PRINTING A
MENISCUS, BUT THE REST OF MY
TALK IS GOING TO FOCUS ON THE
EV-LADEN WOUND DRESSING THAT WE
PRINTED.
SO THERE ARE UNIQUE CHALLENGES
IN OUST TIER AND OPERATIONAL
ENVIRONMENTS.
WOUNDS THAT OCCUR FROM THINGS
LIKE BURNS, BLASTS, GUNSHOTS AND
OTHER TRAUMAS.
LONGER EVACUATION TIME OR
SCENARIOS WHERE EVACUATION MAY
LIMITED OR NOT FEASIBLE AT ALL
COULD BENEFIT FROM PUSHING SOME
OF THESE ADVANCED TECHNOLOGIES
THAT WE'RE ALL DEVELOPING MORE
FORWARD.
IDEALLY TO PUT MORE SCAR-FREE
HEALING SINCE GUARD TISSUE CAN
CAUSE SIGNIFICANT PHYSIOLOGICAL
SIGNIFICANT PHYSIOLOGICAL
CONSTRAINTS, POSSIBLY PRECLUDING
SURGE OR COOL REVISION AND
RECONSTRUCTION FOLLOWING COMPLEX
INJURIES.
OUR SOLUTION WAS TO COMBINE --
THAT COULD BE BIOPRINTED AT THE
POINT OF NEED.
THE EVs WERE DERIVED FROM
MESENCHYMAL STROMAL CELLS AND
THEY WERE STORED IN A FORM ABLE
TO BE RECONSTITUTED AND MIXED
INTO THE BIOLINCC.
THE MAIN ADVANTAGE IS THEY CAN
BE DEPLOYED WITHOUT COLD CHAIN
STORAGE.
ADDITIONALLY, BY BIOPRINTING
THESE BANDAGES, WE CAN CREATE
CUSTOMIZABLE AND
PATIENT-SPECIFIC BANDAGES.
TO ISOLATE THE EVs, WE
RECEIVED MSC CONDITIONED MEDIA.
WE USED SIZE EXCLUSION
CHROMATOGRAPHY IN ORDER TO
ISOLATE THE EVs AND THE MASS
SPECTROMETRY ANALYSIS SHOWED
THAT OUR SAMPLE WAS POSITIVE FOR
KNOWN EV PROTEINS AND THAT WE
HAD OUR HIGH PURITY OF OUR
ISOLATED EVs.
NEXT BE LOOKED NTA OR
NANOPARTICLE TRACING ANALYS
ANALYSIS --.
WE THEN USE 50 MILIMOLAR
PROTECTANT THAT WE DISCOVERED IN
THE LITERATURE.
WE WERE ABLE TO RECONSTITUTE
THEM IN PBS, AND WE CONFIRMED
THIS USING TEM.
BOTH THE FRESH AND THE
RECONSTITUTED EVs.
NEXT WE NEEDED TO EVALUATE THE
PRINTABILITY OF THE ALGINATE CMC
BIOMATERIAL INK.
TO DO THIS, WE CONDUCTED
EX-TENSE SIEVE -- AND SETTLED ON
A -- 4% CMC.
THIS PRODUCED A SHEER THINNING
MATERIAL THAT WAS PRINTABLE.
NEXT WE BIOPRINTED THIS MATERIAL
USING A COMMERCIAL LABORATORY
BASED PRINTER WITH 10%, 20%
INFILL.
PRIOR TO CROSSLINKING WITH
CALCIUM CHLORIDE, THE OUTER
DIMENSIONS OF THE PRINT WERE
SIMILAR TO THAT OF THE CAD FILE.
HOWEVER, WE DID OBSERVE SOME
SWELLING FOLLOWING CROSSLINKING
AND THE PRINT INCREASED IN SIZE
SLIGHTLY.
HOWEVER, THE INTERIOR PRINT
FIDELITY WAS NOT AS GOOD LAKELY
TO OVER -- NON-SCREW-DRIVEN
PRINT HEAD.
WE ALSO OBSERVED THAT THERE WAS
CHANGE OF COLOR OF THE HYDROGELS
AFTER WE CROSS LINKED THEM IN
CALCIUM CHLORIDE.
NEXT WE WANTED TO DETERMINE THE
YOUNGEST MODULUS OR THE
STIFFNESS OF THE RESULTING
HYDROGEL WOUND DRESSING.
THIS IS IMPORTANT BECAUSE
HEALTHY SKIN HAS A STIFFNESS
BETWEEN 5 AND 100 KILL -- CAN I
LA PASCALS AND WE WANTED TO
DESIGN A DRESSING THAT WAS IN
THAT RANGE OF STIFFNESS BECAUSE
IF WE MADE IT MUCH STIFFER THAN
THAT, YOU COULD POTENTIALLY
CAUSE DISCOMFORT OR SECONDARY
TRAUMA.
WHAT WE OBSERVED WAS THAT BOTH
THE 10% AND 20% INFILL WERE
WITHIN THIS RANGE AT
CROSSLINKING OF TIMES BETWEEN
5 AND 60 MINUTES.
HOWEVER, THE 20% INFILL WAS A
LOT EASIER TO HANDLE AND
MANIPULATE AND SO WE DECIDED TO
GO FORWARD WITH THAT DESIGN.
NEXT WE FLUORESCENTLY LABELED
EVs USING A DYE.
CONNECTING THEM WITH A LURE
ADAPTER AND SLOW SLEE MIXES BACK
AND FORTH.
AFTER PRINTING WE SAW THE EVS
WERE WELL DISTRIBUTED AND WE
SELECTED A CON 16 LAITION -- PER
MICRO LITER WOUND -- THIS WAS
TAKEN FROM LITERATURE REPORTED
VALUES.
NEXT WE WANTED TO LOOK AT EV
RELEASED FROM THE HYDROGEL WOUND
DRESSING.
TO DO THIS, WE 3D PRINTED A
COLLAGEN SKIN SUBSTITUTE.
SINCE SKIN IS PREDOMINANT RI PRY
COMPOSED OF COLLAGEN.
WE EVALUATED 10 MINUTE
CROSSLINKING TIME AND 60 MINUTE
CROSSLINKING TIME AND OBSERVED
THERE WAS A DIFFERENCE IN NUMBER
OF EVs THAT WERE RELEASED
BASED ON CROSSLINKING TIME.
THIS IS VERY PROMISING, HOWEVER
WE HAVEN'T BEEN ABLE TO COMPLETE
THIS WORK YET AND THIS IS AN
AREA OF FUTURE EFFORT.
NEXT WE 3D PRINTED THE EV LADEN
HYDROGEL WOUND DRESSING IN THE
ARCTIC ENVIRONMENT.
WE ACTUALLY TRAINED A SERVICE
MEMBER -- AND MIX THEM USING THE
PROCESS I DESCRIBED EARLIER.
WE THEN BIOPRINTED THE WOUND
DRESSING HYDROGEL ON TO A PLA
THERMAL PLASTIC BACKING, AND WE
DESIGNED TWO DIFFERENT FORMATS.
SO WE HAD A LARGER FORMAT, WHERE
THE BIOACTIVE WOUND DRESSING WAS
PRINTED IN THE CENTER.
WE INCLUDED A FLEXIBLE PLA
BACKING THAT CAN BE CONFORMED TO
TO DIFFERENT JOINT AND
GEOMETRIES, AND WE INCLUDED AN
ADHESIVE REGION ON THE OUTER
EDGES SO THAT THE BANDAGE WOULD
STAY IN PLACE.
SO IN SUMMARY, I'VE TALKED TO
YOU ABOUT SOME OF THE CHALLENGES
ASSOCIATED WITH CONTESTED
LOGISTICS ENVIRONMENTS.
I'VE TALKED ABOUT HOW ADDITIVE
MANUFACTURING AT THE POINT OF
NEED IS A POTENTIAL SOLUTION.
I PRESENTED TWO OPTIONS FOR
LOGISTICS AND TRANSPORTS OF
THESE PRINTERS TO AUSTERE
LOCATIONS, AND TALKED ABOUT
PRINTING THERMAL PLASTIC PARTS
AND BIOPRINTING ADVANCED
THERAPEUTICS IN THESE LOCATIONS.
AND WITH THAT, I'D LIKE TO
ACKNOWLEDGE DR. VINCE HO, OUR
CENTER DIRECTOR AND THE P.I. ON
THIS GRANT.
AND ALSO DR. NICHOLAS SHAR
TRAIN, WHO DEPLOYED TO ME TO THE
ARCTIC ENVIRONMENT TO CONDUCT
THIS WORK AND HE IS ALSO IN THE
AUDIENCE TODAY.
I'D LIKE TO ALSO ACKNOWLEDGE THE
SERVICE ACADEMY STUDENTS WHO
JOINED US FOR FIVE-WEEK RESEARCH
ROTATIONS DURING THE SUMMER.
WE HAD A KA GET FROM EACH OF THE
SERVICE ACADEMIES, FINALLY, OUR
FUNDING SOURCES.
[APPLAUSE]
>> THAT IS GREAT.
THANK YOU.
THIS PAPER IS OPEN FOR QUESTIONS
AT THE MIC.
>> REALLY GREAT WORK, THANK YOU.
I KNOW THIS IS FOCUSED ON
BIOMATERIALS AND TISSUE
ENGINEERING OR INJURY
APPLICATIONS, BUT I WONDER IF
YOU HAVE ALSO THOUGHT ABOUT
DIAGNOSTIC -- A COLLEAGUE OF
MINE HAD A GRANT FROM DARPA TO
DO POINT OF CARE -- TO AT LEAST
EXPLORE POINT OF CARE DEVICES
THAT COULD BE -- LIKE YOU COULD
BUILD THE DEVICE LOCALLY VERY
QUICKLY, INCLUDING PUTTING THE
PRIMERS AND ALL OF THE REAGENTS
TO BE ABLE TO PRODUCE A POINT OF
CARE DEVICE FOR EPIDEMIC.
SO I DON'T KNOW IF YOU'VE
THOUGHT ABOUT SORT OF DIFFERENT
APPLICATIONS AS WELL FOR USING
THE 3D PRINTING FOR PERHAPS
DIAGNOSTIC APPLICATIONS.
>> THANK YOU FOR BRINGING THAT
UP.
THAT'S VERY INTERESTING AND NOT
SOMETHING THAT WE HAVE DIRECTLY
DONE TO DATE.
HOWEVER, THE PRINTER THAT WE
DEPLOY THAT IS BUILT TO THESE
RUGGEDIZED SPECIFICATIONS IS
CAPABLE OF VERY PRECISE
DISPENSING, AND CAN ALSO PRINT
ELECTRICALLY CONDUCTIVE INK AND
THERE IS A TOOL WHERE YOU CAN
PICK AND PLACE COMPONENTS.
AND SO LOVE TO TALK TO YOU MORE
ABOUT THAT.
>> SO THE LAST COMMENT/QUESTION
FOR YOU, I JUST RECENTLY SAW A
TALK, I SAW YOU HAD SOME
COLLAGEN SKINNY EQUIVALENT.
I RECENTLY SAW A TALK WHERE THEY
HAD INNERVATED SKIN GROWING IN
WELL PLATES, CURIOUS IF YOU
THOUGHT ABOUT USING THAT AS ONE
OF YOUR TEST BEDS, A WOUND
HEALER DEVICE.
>> YES, I WOULD BE VERY
INTERESTED IN HAVING A FURTHER
CONVERSATION AND THAT MIGHT BE
AN EXCELLENT OPPORTUNITY FOR
PARTNERSHIP.
>> GREAT.
LET'S THANK OUR SPEAKER, PLEASE.
THANK YOU.
[APPLAUSE]
ALL RIGHT.
NOW WE'VE GOT ALL OF THE OTHER
SPEAKERS OUT OF THE WAY.
CAN YOU PLEASE LOAD MY 200 SLIDE
DECK TO THE -- SO I CAN, QUOTE,
CLOSE THIS OUT FOR THE NEXT TWO
HOURS?
NO, OBVIOUSLY NOT.
I DO WANT TO THANK EVERYONE, SO
I DO WANT TO MAKE SOME FINAL
REMARKS AND SAY SOME THANK YOUS.
WOW, THAT WAS REALLY SOMETHING
OF A DAY, THIS WAS A GREAT DAY.
SO I JUST DO WANT TO SAY HOW
THIS KIND OF GOT STARTED.
I STARTED HERE AT NIH 19 MONTHS
AGO, I'M STILL COUNTING.
SOMEONE TELL ME WHEN I HIT MY
TODDLER YEARS TOO, THEN I'LL
STOP COUNTING.
I DON'T LIKE CHANGE, IT'S BEEN A
MASSIVE CHANGE BUT A GOOD ONE.
AND ABOUT 18 MONTHS AGO, I WAS
SPREADING THE GOOD NEWS AND THE
GOOD WORD ABOUT DATA CENTER AND
GETTING EVERYBODY ON CAMPUS
EXCITE AND THINKING HOW DO WE
REACH THE EXTRAMURAL COMMUNITY,
OH, MY GOODNESS, THE BME
CONFERENCE IS IN BALTIMORE IN
2024, SO WE SHOULD HAVE A BIG
IMPACT AT THE BIOENGIN BIOMEDICL
ENGINEERING SOCIETY CONFERENCE.
CAITLYN SADL ER, NIBIB
INTRAMURAL RESEARCHER SAID OH,
HOW ABOUT WE HAVE A DAY AT THE
NIH?
THE DEPUTY DIRECTOR OF THE DATA
CENTER RESERVED THE MASUR
AUDITORIUM THAT DAY 18 MONTHS
AGO AND THEY WE WERE OFF FOR THE
NEXT EA 18 MONTHS.
BUT I'M SUPER GLAD YOU'VE BEEN
ABLE TO JOIN US.
THERE ARE SEVERAL PEOPLE I WOULD
LIKE TO THANK BEFORE I GET TO MY
FINAL THOUGHTS.
SHE DIDN'T GET MAIN STAGE BUT I
WOULD LIKE NICOLE MORGAN TO
PLEASE STAND UP.
SHE DOESN'T LIKE THIS KIND OF
ATTENTION BUT THAT'S FINE, SHE
NEEDS TO GET IT.
THAT'S GREAT.
[APPLAUSE]
YOU CAN LEAVE THE LIGHTS OUT.
NICOLE MORE DPA MORGAN IS DEPUTR
OF THE DATA CENTER, SHE HAS BEEN
NIH GREATER LENGTH OF TIME BUT
SHE'S BEEN A GREAT RESOURCE TO
ME LEARNING HOW THIS PLACE WORKS
AND ALSO TO GET THIS OFF THE
GROUND.
IS ARE HAVE BEEN TRAVELING,
DOING OTHER THINGS.
NICOLE LOVES EMAIL, I DO NOT.
THOSE OF YOU WHO KNOW ME KNOW
THAT TO BE TRUE AND I'M REALLY
THANKFUL OF HOW SHE'S BEEN ABLE
TO KEEP THESE THINGS GOING
DURING THIS.
SO COULDN'T HAVE DONE IT WITHOUT
HER.
SHE IS DEFINITELY KEY.
OBVIOUSLY I HAVE TO THANK BRUCE
TROMBERG, DIRECTOR OF NIBIB.
HE'S A VISIONARY, HE LET'S US
BRING THESE SYRINGES TO LIKE AND
HE EMPOWERS THE TEAM TO ALLOW US
TO DO THAT.
WANT TO THANK THE FOLKS WHO ARE
KEY ON THE EXTRA MILLER SIDE, SO
THEY COULD BRING ALL OF THESE
WONDERFUL PROGRAM DIRECTORS HERE
TO BE ON SITE TO MEET WITH YOU
WONDERFUL VISITORS, AND ALSO
WANT TO THANK THOSE FROM THE
OTHER INSTITUTES AND CENTERS.
MANY WILL BE COMING TO THE
CONFERENCE IN BALTIMORE SO SWING
WHICH OUR NIBIB EXHIBITOR BOTH
IF YOU DIDN'T GET TO TALK TO A
PROGRAM DIRECTOR AND WE'LL HAVE
MORE THERE AS WELL.
I DO NEED TO THANK MY LAB
BECAUSE THEY LOSE ME AS WE DO
ALL OF THESE BETA CENTER EVENTS,
AND MY LAB HAS BEEN GROWING
OBVIOUSLY OVER THE LAST 18
MONTHS WHICH HAS HAD GREATER
REQUIREMENTS SO I AM
APPRECIATIVE OF THEM, AND I WANT
TO THANK TH THE DATA CENTER STAF
MEMBERS WHO HAVE ALSO BEEN
BEHIND THE SCENES KEEPING THIS
GOING BUT ALSO OUR CONTRACTING
GROUP FROM SYNERGY, SUSAN
HOLBROOK, JESSICA, JULIE AND
THEN THEY BROUGHT SOME EXTRA
EMPLOYEES WITH THEM TODAY.
ONCE THEY CAME ON BOARD OUR
BRAIN SPACE WAS ABLE TO THINK
ABOUT THE SCIENCE, AND ALL THE
OTHER LOGISTICS WERE GOING TO
THEM.
SO I WANT TO THANK THEM AGAIN
FOR THAT.
AND RICHARD LEITMAN, SCIENTIFIC
DIRECTOR FOR NIBIB, HE'S LIKE
DEPARTMENT CHAIR, HE'S ANOTHER
SUPPORTER OF THESE ACTIVITIES
THAT WE'RE TRYING TO DO TO BUILD
BIOENGINEERING AT THE NIH
CAMPUS, AND AGAIN, I HOPE YOU
ALL ARE GETTING THIS MESSAGE
THAT JUST BECAUSE WE ARE BEHIND
THIS WELL SECURED GATED
ENVIRONMENT THAT YOU ALL HAVE
COME THROUGH, WE ARE ABLE TO
REACH ACROSS THE GATE AND
COLLABORATE AND WORK WITH YOU
ALL ON OUTSIDE, AND WE SEEK TO
DO THAT.
SO DON'T LET THESE WALLS FOOL
YOU.
THEN JUST AS I CLOSE OUT AGAIN,
WANT TO THANK ALL THE TOUR
GUIDES.
THEY'VE OPENED UP THEIR SPACES
AND WERE RESPONSIVE TO OUR
WONDERFUL QUESTIONS.
I WANT TO THANK THE ABSTRACT
REVIEWERS.
WE DID HAVE A PROCESS TO MAKE
THOSE DECISIONS.
I WANT TO THANK THE NIBIB
COMMUNICATIONS OFFICE FOR
GETTING OUR WEBSITE GOING,
HELPING US DESIGN SOME OF THE
INITIAL GRAPHICS, AND THEN
MAKING SURE THEY CAN DO THE
UPDATES AS WE WERE ABLE TO
INFORM YOU ALL.
AND THEN JUST TO END WITH WHAT I
TOOK HOME AS A MESSAGE BRIEFLY
IN CASE YOU MISSED IT.
SO I THINK THERE WERE A FEW CALL
TO ARMS.
IT OPENED UP WITH
DR. BERTAGNOLLI AND I TOLD HER
WE HAD A PREMEETING AND I WAS
LIKE WHATEVER YOU REALLY WANT
PEOPLE TO WORK ON, THROW IT OUT
THERE IN YOUR CONVERSATION.
AND SHE HAD SAID SOMETHING TO US
THEN AND SHE REPEATED IT HERE
AND I HOPE YOU CAUGHT IT.
THERE IS A REAL NEED, SHE REALLY
GOT EXCITED THINKING ABOUT HOW
WE NEED THIS, TO IDENTIFY AND
DETECT REPLICATING VIRUS IN
TISSUES.
SHE SAID THAT TO BRUCE AND I A
COUPLE DAYS AGO AND SHE POUNDED
IT AGAIN HERE.
SO THOSE OF YOU THINKING ABOUT
THESE KIND OF DIAGNOSTICS AND
TECHNOLOGIES, THIS IS WHAT SHE'S
PUSHING FOR.
HIV HAS BEEN -- THAT COMMUNITY
HAS BEEN TRYING TO DO THAT FOR A
LONG TIME TO FIND THESE LATENT
VIRUSES IN THESE RESERVOIRS.
NOW WITH COVID AND LONG COVID AS
SHE MADE CLEAR, THIS IS A HUGE
BIOMEDICAL NEED THAT IF YOU HAVE
TECHNOLOGIES THAT YOU CAN THINK
ABOUT, YOU GOT THE NIH DIRECTOR
SAYING THAT IS A PRIORITY.
OTHER PRIORITIES THAT CAME UP,
THIS CAME UP FROM DR. TISDALE,
OUR EARLY MORNING PLENARY,
BETTER POISONS BUT BETTER
DESTRUCTION FOR ABLATION
PROTOCOLS FOR A NUMBER OF
BENEFITS OF HOW IT CAN IMPACT
PATIENTS, CANCER, SICKLE CELL
AND OTHER.
WAYS OF THINKING ABOUT FERTILITY
PRESERVATION AND REA PRODUCTIVE
HEALTH, ESPECIALLY THOSE THAT
HAPPEN TO PEOPLE WHEN THEY'RE
CHILDREN THAT AREN'T ABLE TO
MAKE THAT DECISION.
AND WE HEARD THAT COMPLICATING
FACTOR OF ASSENTING THEM BUT
PARENT WAITING UNTIL THEY WERE
THE AGE OF CONSENT BUT THEN YOU
HAVE RISKS OF THE TRANSPLANT
TAKING.
ANNOTATED DATA, WE'RE ALL
COLLECTING AMOUNTS OF RNA SEQ,
AND WHAT WE HEAR IS A
COMPLICATION, HOW DOES ONE
PERSON USE SOMEONE ELSE'S DATA?
IT'S NOT WELL ANNOTATED.
IF IT'S NOT IN UNIFORM FORMAT,
IT REALLY MAKES IT CHALLENGING
AND DIMINISHES THE POW WE ARE WE
CAN GET FROM HARNESSING ALL OF
THAT DATA.
WE LEARNED THIS AFTERNOON, BLOOD
CULTURES FOR SEPSIS TAKE TOO
LONG.
HE'S GOT IDEAS ON HOW TO MAKE
THEM FASTER BUT WHAT ARE THE
WAYS THAT YOU MIGHT BE ABLE TO
ADD?
ADD
VALUE TO THAT.
I HOPE YOU ALL LEARNED THAT
DRIED BLOOD MATRIX REALLY SERVES
AS AN INTERESTING BIOMATERIALS
THAT ALLOWS ENABLING
BIOCHEMISTRY THAT MAYBE WE
WEREN'T THINKING.
THEN ANOTHER INDUSTRY PANEL,
THIS BLEW MY MIND, HOLDING ON
TOO TIGHTLY, TO THE CON SECHT
THAT IT'S MY IDEA AND I WANT TO
KEEP ALL THE CREDIT AND
THEREFORE ALL THE EQUITY AND
MONEY THAT WILL PRESUMABLY COME
FROM THIS.
BUT THAT'S A LIMITATION IF YOU
DON'T GET THE RIGHT TEAM MEMBERS
ON BOARD.
THEN THE OTHER BIG MESSAGE I
THINK WAS BROAD PLI AGREED UPON,
UPON THAT PANEL, LATER PUNCHED
HOME LATER IN DR. BASHIR'S
WONDERFUL PRESENTATION IS TO
THINK ABOUT MANUFACTURING EARLY
IN YOUR PROCESS.
WE ALL WANT TO GET THINGS TO
HELP PEOPLE BUT THERE ARE
SEVERAL STEPS IN BETWEEN THAT
WE'RE NOT THINKING ABOUT, THOSE
CAN BECOME THE BIG HURDLES, AND
DR. BASHIR GAVE EXCELLENT
EXAMPLES OF HOW THAT CAN BE
ESPECIALLY IMPORTANT WHEN
WORKING WITH INTERNATIONAL
COMMUNITIES OR IN LOW AND MIDDLE
INCOME COUNTRIES THAT DON'T HAVE
ALL THE RESOURCES THAT YOU
ASSUME WOULD BE AVAILABLE TO%RN
WHAT YOU'RE DOING.
SO THAT'S JUST THE BEGINNING.
HOPEFULLY I WILL SEE MANY OF YOU
AT THE BMES CONFERENCE.
IF NOT, WE ARE GLAD THAT YOU
CAME TO OUR BETHESDA SPACE.
THIS IS YOUR SPACE, YOUR FEDERAL
TAX DOLLARS SUPPORT IT.
YOU SUPPORT OUR RESEARCH.
YOU'RE WELCOME TO JOIN US ANY
TIME, AS LONG AS YOU PAY
ATTENTION TO THE RULES AT THE
GATEWAY SECURITY, AND THE BETA
CENTER REALLY WANTS TO BE A HUB
THAT IF YOU WANT TO CONNECT WITH
OTHER RESEARCHERS HERE IN THE
INTRAMURAL PROGRAM, REACH OUT TO
US, INTRAMURAL FOLKS IF YOU WANT
TO CONNECT OUT BROADLY,
HOPEFULLY YOU MADE A FRIEND
TODAY BUT WE'RE HAPPY TO HELP
FACILITATE THOSE CONNECTIONS IFN
THE FUTURE.
SO THANK YOU ALL FOR A WONDERFUL
DAY, HAVE SAFE TRAVELS TO
BALTIMORE, THOSE THAT ARE GOING,
AND MEET NEW FRIENDS ON THE WAY
OUT.
THANKS A LOT.
[APPLAUSE]