IT'S A PLEASURE TO
>> THANK YOU.
IT'S A PLEASURE TO SEE YOUR
BRIGHT SHINING FACES.
MY NAME IS MELISSA PARISI AND I
LEAD THE NIH INCLUDE PROJECT AND
WE HAD OVER 270 WHO REGISTERED
SO WE'RE EXCITED TO HAVE YOU ALL
HERE.
I THOUGHT I'D GET AUDIENCE
PARTICIPATION FOR STARTERS.
HOW MANY ARE HERE FOR THE FIRST
TIME.
WELCOME.
IF YOU GET TO SEE THE HALL OF
NOBEL LAUREATES IT'S GREAT IT'S
WONDERFUL BUT BE HERE FOR THE
SESSIONS.
ALL RIGHT.
I'M GOING KICK THINGS OFF FOR
OUR FIRST SESSION AND GIVE A FEW
HOUSEKEEPING REMARKS TO START US
OFF.
WE'RE GOING TO HAVE DR. DI
DR. DIANNE -- DIANA BIANCHI AND
WE'LL GIVE INTRODUCTION TO WHAT
HAS BEEN GOING ON WITH THE
INCLUDE PROJECT FOR THE PAST
FIVE YEARS.
I WANTS TO MAKE SURE EVERYBODY
HAD A CHANCE DOWNLOAD THE
SCHEDULE OR REVIEW THE SCHEDULE
WITH YOU VERY BRIEFLY.
THERE'S A QR CODE ON POSTERS
OUTSIDE THE AUDITORIUM IF YOU
WANT A MORE DETAILED VERSION OF
THE AGENDA.
WE'RE TRYING TO SAVE PAPER AND
TREES SO WE DIDN'T PRINTOUT A
LOT OF COPIES.
FIRST, WE'LL HAVE SESSIONS.
WE NUMBERED THESE IN ORDER.
MANY ARE PANEL DISCUSSIONS.
WE'RE HOPING TO HAVE FORMAL
PRESENTATIONS FOLLOWED BY
DISCUSSION AND Q&A.
SO THIS IS WHERE WE'RE GOING
NEED AUDIENCE PARTICIPATION.
WE'LL HAVE SEVERAL BREAKS WITH
REFRESHMENTS AVAILABLE DURING
THE BREAKS AND IMPORTANTLY,
LUNCH, BECAUSE WE'LL BE HUNGRY
AND HAVE BOX LUNCHES BOTH DAYS
START AT NOON.
HOWEVER, LUNCHEON TOMORROW'S
DATE WILL ALSO HAVE BREAKOUT
SESSIONS.
WE WANT YOU TO BE PARTICULARLY
EFFICIENT ABOUT GETTING YOUR
LUNCHES TO CHOOSE A BREAKOUT
GROUP TO JOIN FOR DISCUSSION
DURING THE LUNCH PERIOD.
I WANT TO POINT OUT WE HAVE A
POSTER SESSION STARTING AT 3:30
AND WE'RE PROUD AND EXCITED BY
THIS POSTERS THAT ARE GOING TO
BE PRESENTED AND THERE WILL BE
REFRESHMENTS AVAILABLE AS WELL
AS INCENTIVE TO KEEP YOU LOOKING
AT THE POSTERS AND TALK WITH THE
HARD WORKING INVESTIGATORS WHO
PREPARED THEM.
A LITTLE BIT OF HOUSEKEEPING.
WE'LL BE FOCUSSING ON DOWN
SYNDROME RESEARCH AND BASIC
CLINICAL TRIALS AND WE'LL HAVE
TIME KEEPERS SITUATED LETTING
YOU KNOW WHEN THERE'S THREE OR
FIVE MINUTES LEFT.
IF YOU HAVE QUESTIONS YOU'LL SEE
THE TWO MICROPHONES IN THE
AISLES.
LINE UP BEHIND THOSE TO PROVIDE
YOUR QUESTIONS AND/OR DISCUSSION
ITEMS.
I MENTIONED THE BOX LUNCHES AND
FOOD AND WE APPRECIATE EVERYONE
WORKING TOGETHER TO MAKE SURE IT
WILL BE A GREAT MEETING.
I WANTED TO HIGHLIGHT THE
SPEAKER WHO'S ARE SELF-ADVOCATES
WITH DOWN SYNDROME.
THE FIRST IS MR. ISAIAH LOMBARDO
I'LL INTRODUCE LATER AND MS.
AGUSTA AGWARD AND MR. DAVID
EAGAN AND HE'LL INTRODUCING
DR. ESPINOZA TOMORROW.
WE'RE GRATEFUL FOR OUR
SELF-ADVOCATES WHO HAVE JOINED
US TALKING ABOUT THE CONTINUING
TO OF DOWN SYNDROME SO RELEVANT
TO THEIR LIVES.
FINALLY, I'D LIKE TO THANK OUR
INCLUDE AMBASSADORS.
WHEN YOU JOINED US THIS MORNING
YOU WERE PROBABLY GREETED WITH
PIA AND GABBY AND THEY'RE IT
THREE AMBASSADORS WHO
VOLUNTEERED THEIR TIME TO
WELCOME EVERYBODY TO THE
MEETING.
THANK YOU VERY MUCH TO PIA,
GABBY AND THERESA AS WELL.
ALL RIGHT.
SO WITHOUT FURTHER ADO, I'D LIKE
TO INTRODUCE MY BOSS, DR. DIANA
BIANCHI.
SHE IS THE DIRECTOR OF THE
EUNICE KENNEDY SHRIVER NATIONAL
INSTITUTE OF CHILD HEALTH AND
HUMAN DEVELOPMENT AND OVERSEES
AN ANNUAL BUDGET OF ABOUT $1.6
BILLION AS PART OF NICHD'S
MISSION TO UNDERSTAND HUMAN
DEVELOPMENT, ENHANCE THE CHILD
OF CHILD AND ADOLESCENTS AND
OPTIMIZE ABILITIES FOR ALL.
DR. BIANCHI IS FOR THE CENTER OF
PRECISION HEALTH RESEARCH WHERE
SHE DOES RESEARCH ON PRENATAL
THERAPIES FOR GENETIC DISORDERS
FOR THE AUSPICES OF THE HUMAN
GENOME INSTITUTE.
ANOTHER INSTITUTE HERE AT NIH.
SHE IS A MEMBER OF THE NATIONAL
ACADEMY OF MEDICINE AND HAS A
LONG LIST OF AWARDS AND
ACCOLADES.
I ENCOURAGE TO YOU GO TO THE WEB
SATE FOR THE MEETING TO GET MORE
DETAILS AND IMPORTANTLY CO-CHAIR
OF THE NIH INCLUDE STEERING
COMMITTEE WHERE SHE HELPS GUIDE
THE INCLUDE INITIATIVE.
DR. BIANCHI, YOU'RE UP.
>> THANK YOU FOR THE KIND
INTRODUCTION AND IT'S MY
PARTICULAR TO STEER THE
COMMITTEE WITH DR. HODES THE
DIRECTOR OF THE NATIONAL
INSTITUTE ON AGING AND DR. GARY
GIBBONS THE DIRECTOR OF THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE AND WE'RE SUPPORT
FANTASTIC STAFF, PROGRAM
OFFICIALS, MEDICAL OFFICERS AND
THEY MAKE THIS HAPPEN.
I CAN'T TELL YOU HOW EXCITING IT
IS TO SEE ALL OF YOU HERE AND
PARTICULARLY THE FACT THAT SO
MANY OF YOU HAVE NEVER BEEN TO
THE NIH CAMPUS BEFORE.
SO I FEEL LIKE IN A WAY WE'RE
ACCOMPLISHING OUR GOAL JUST BY
THE FACT THAT YOU ARE HERE WE'RE
CREATING THIS COMMUNITY OF
RESEARCHERS DEDICATED TO
ADVANCING THE HEALTH OF PEOPLE
WITH DOWN SYNDROME.
IN MY BRIEF REMARKS -- I'M JUST
GOING TO REMIND EVERYONE AND
YOU'RE QUITE FAMILIAR WITH THE
PROGRAM AND I'LL REMIND YOU THE
PROGRAM STARTED WITH A
PRESENTATION AND IMPRESSED THEM
THEY GAVE THE MEMBERS OF
CONGRESS GAVE HIM A STANDING
OVATION AND THAT CAUSED AN
INFLEXION IN FUNDING FOR DOWN
SYNDROME RESEARCH.
THAT WAS IN BELIEVE I 2017,
WHICH THEN LED TO DISCUSSIONS IN
THE SPRING OF 2018, I BELIEVE IT
WAS, HOW ARE WE GOING SPEND THIS
MONEY.
AND THAT WAS THE GENESIS OF THE
INCLUDE INITIATIVE.
WHAT WE DISCUSSED AT THE TIME
WAS TO CREATE THREE PROGRAM
COMPONENTS.
ONE WAS TO ADVANCE HIGH RISK,
HIGH REWARD BASIC SCIENCE
RESEARCH ON CHROMOSOME 21.
ONE WAS THE NEED TO ASSEMBLE A
LARGE STUDY POPULATION OF
INDIVIDUALS WITH DOWN SYNDROME
ACROSS THE LIFE SPAN.
OF COURSE THERE HAD BEEN SMA
SMALLIES BUT HAD NEVER BEEN --
SMALL STUDIED BUT NEVER COMBINED
DO CREATE A BIG DATA SET AND
DOWN SYNDROME WAS AN EXCLUSION
FROM MANY CLINICAL TRIALS THAT
INVOLVED MEDICATIONS PEOPLE WITH
DOWN SYNDROME NEEDED SO THE
THIRD AIM WAS PEOPLE TO INCLUDE
INDIVIDUALS IN SKIFTH AND FUTURE
CLINICAL TRIALS.
SUPPORT FROM -- EXISTING AND
CLINICAL TRIALS.
THE SUPPORT CONTINUED TO
INCREASE AND IT'S FLAT THIS YEAR
BUT HAPPY IT WASN'T CUT.
IN FISCAL YEAR '23 NIH INVESTED
$90 MILLION IN DOWN SYNDROME AND
MORE THAN 330 PROJECTS HAVE BEEN
FUNDED.
YOU CAN SEE THAT AT THE WEBSITE.
WE SHOULD THANK CONGRESS FOR
THEIR INCREDIBLE SUPPORT AND OF
COURSE THAT'S PARTLY DUE TO THE
INCREDIBLE ADVOCACY THAT HAS
BEEN DEMONSTRATE A NUMBER OF
GROUPS I'M JUST GOING GIVE BRIEF
SNAPSHOTS.
I OBVIOUSLY CANNOT ACKNOWLEDGE
ALL THE WONDERFUL WORK BY THE
PEOPLE IN THIS ROOM.
I LOOK FORWARD TO THE
PRESENTATIONS AND THE POSTERS.
IF YOU HAVE FANTASTIC BREAKING
NEWS YOU NEED IT TELL US ABOUT,
WE EXPECT TESTIMONIES IN
CONGRESS BY NIH WILL PROBABLY BE
OCCURRING IN MAY.
SO IF THERE'S ANECDOTES WE
SHOULD KNOW ABOUT, PLEASE FEEL
FREE TO SHARE THEM.
WE SELECTED A FEW.
IN AIM ONE, IT'S FOCUSSED ON
BASIC TRANSLATIONAL AND
DISCOVERY SCIENCE.
IT'S FOCUSSED ON BIOMARKERS FOR
EXAMPLE FOR ALZHEIMER'S DISEASE
TO IDENTIFY RISK FACTOR AND TO
CREATE CLINICAL TRIALS.
PART OF THE BASIC SCIENCE WORK
WAS FOR PRE CLINICAL MODELS
INCLUDING ANIMAL MODELS AS WELL
AS PLURIPOTENT STEM CELLS AND
THEY'RE INVESTIGATING CONDITIONS
ACROSS THE LIFE SPAN TO
UNDERSTAND DOWN SYNDROME AND TO
UNDERSTAND IN PARTICULAR WHY
PEOPLE WITH DOWN SYNDROME ARE
MORE PRONE TO CONDITIONS LIKE
ALZHEIMER'S DISEASE BUT
PROTECTED FROM OTHER CONDITIONS
SUCH AS MYO CARDIAL INFARCTION.
ONE HIGHLIGHT THAT WAS SELECTED
IS THIS FROM THE GROUP OF YOUNG
ET AL. CREATED MOLDS OF NEURAL
HUMAN TISSUES THAT HAVE
FUNCTIONAL CONNECTIVITY.
WE NEED BETTER MODELS TO
UNDERSTAND THE NEURAL PATHOLOGY
IN DOWN SYNDROME.
SO THEY DEVELOPED A 3-D BIO
PRINTING PLATFORM THAT ARE ALONG
WITH THE COMMERCIAL BIO PRINTER.
THEY EXHIBIT FUNCTIONAL HUMAN
NEURAL TISSUES WITH NEURAL
CIRCUITS BETWEEN DEFINED NEURAL
SUB TYPES AND FUNCTIONAL
CONNECTIONS BETWEEN CORTICAL AND
T
TRIATAL TISSUE AND DESTRUCTION
OF MYELIN.
THE THINKING IS THAT THIS TYPE
OF BIO PRINTING MODEL MAY BE
EXTREMELY USEFUL IN DOWN SIN
DRO
DROME.
THE MECHANISMS OF AUTO IMMUNITY
HAVE BEEN DEMONSTRATED IN THE
PAPER IN NATURE.
WITH KNOW PEOPLE WITH DOWN
SYNDROME ARE PRONE TO SEVERE IN
TENSIONS AND AUTO IMMUNE
CONDITIONS AND THEY INVESTIGATED
MECHANISMS UNDERLYING AUTO
IMMUNE SUSCEPTIBLE LOOKING AT
THE HAND SCAPE AND SHOWED
PERSISTENT ELEVATION OF UP TO 22
CYTOKINES AT A STEADY STATE.
THIS IS POINTING TOWARDS
POSSIBLE THERAPEUTIC AVENUES
USING BROAD IMMUNOSUPPRESS AND
THEANT -- IMPRESSANTS LIKE JAK
INHIBITERS AND WE LOOK AT
INDIVIDUALS FROM BIRTH TO SENIOR
AGES.
AND IMPORTANT FOR THIS WORK IS
THE ALZHEIMER'S BIOMARKER
CONSORTIUM DOWN SYNDROME ALSO
KNOWN AS ABCDS.
SOME OF THE EXAMPLES OF WHAT
THESE GROUPS ARE DOING NAR
THEY'RE IT LOOKING AT PET
SCANNING OF INDIVIDUALS WITH
DOWN SYNDROME AND ESTIMATING
EMERGENCE OF AMYLOID AND TAU
BURDEN IN DOWN SIN DOME AND
CO-ENROLLING IN THE DOWN
SYNDROME OR TRCDS THAT WILL
RECRUIT FOR CLINICAL TRIALS IN
ALZHEIMER'S DISEASE.
SOMETHING NEW THIS YEAR AIMS
TOWARDS LARGE POPULATIONS OF
PEOPLE WITH ALL AGES WITH DOWN
SYNDROME.
THEY REARE CEUTING PEOPLE WITH
DOWN SYNDROME ACROSS THE LIFE
SPAN COLLECTING BIO SPECIMENS
AND DOING OMICS STUDIES FOR DEEP
PHENOTYPING AND ALL THE DATA
WILL BE PUBLICALLY AVAILABLE TO
THE SCIENTIFIC COMMUNITY.
AND THIS WILL CONSISTENT OF CHIN
CAL SITES, COORDINATING CENTERS
AND A SIMPLED BIO REPOSITORY.
FOR AIM THREE, AGAIN BRIEF
HIGHLIGHTS.
THESE ARE THE CLINICAL TRIALS
INCLUDING PEOPLE WITH DOWN
SYNDROME.
SO TREATMENT WITH JAK INHIBITORS
CAN REDUCE INTERFERON-BASED
INFLAMMATION.
THESE ARE SHOWING POTENTIAL
BENEFITS FOR AUTO IMMUNE AND
OTHER DISORDERS COMMON TO PEOPLE
WITH DOWN SYNDROME WE MAY HEAR
ABOUT LATER IN THE DAY.
AND THE COMBINATION OF ATO
OXYHAS BEEN IDENTIFIED AS A
PROMISING TREATMENT FOR
OBSTRUCTIVE SLEEP APNEA IN
CHILDREN WITH DOWN SYNDROME AND
SPEAKING OF SLEEP APNEA, THE
FEASIBILITY AND PERFORMANCE OF
TESTING AT HOME IS A MAJOR
SUCCESS OF THE INCLUDE
INITIATIVE.
SO NOBODY WANTS TO GO INTO A
HOSPITAL OR CLINIC AND BE TESTED
FOR SLEEP APNEA.
YOU NEVER SLEEP WELL.
I KNOW THAT FOR A FACT.
MY HUSBAND HAS HAD SLEEP STUDIES
AND COMPLAINED NON STOP ABOUT
THEM.
NOT ONLY THAT, AS THE A DEARTH
OF SLEEP LABORATORIES CAPABLE OF
DOING THIS TESTING PARTICULARLY
IN YOUTH WIN NEUROCOGNITIVE
DISABILITIES.
IN THIS STUDY IN THE JOURNAL OF
CLINICAL SLEEP MEDICINE THE ERS
TEST THE FEASIBILITY,
ACCESSIBILITY OF IN HOME LEVEL 2
SLEEP APNEA TESTING VERSUS POLY
SOMNOGRAPHY AND TESTS FEMALES
AND FEMALES AND 41 OF THEM
COMPLETED THE HOME TESTING AND
41 COMPLETED THE OTHER.
40 OF THE PEOPLE UNDER WENT BOTH
TESTS AND THE HOME SLEEP STUDY
WAS DETERMINED TO BE WELL
TOLERATED, RELIABLE AND
PREFERABLE.
WANT TO SLEEP IN YOUR OWN BED IF
YOU CAN TO HOSPITAL SLEEP
STUDIES TO IDENTIFIED SLEEP
APNEA.
THIS IS A MAJOR ADVANCE
PARTICULARLY FOR YOUTH SUSPECTED
TO HAVE SLEEP APNEA.
I FORGOT TO MENTION OWN THE
FIRST SLIDE WHEN I SHOWED THE
VEN DIAGRAM THERE'S TWO OTHER
COMPONENTS OF THE INCLUDE
INITIATIVE.
ONE IS THE CREATION OF NEW
RESOURCES THAT CAN BE USED BY
ALL.
AND THE OTHER IS TO INCREASE THE
WORKFORCE.
WE'LL BE HEARING IF THE INCLUDE
DATA HUB WHICH HAS BEEN A
TERRIFIC RESOURCE.
IT'S CLOUD-BASED.
IT'S BEEN DEVELOPED THROUGH THE
COORDINATING CENTER AND PROVIDES
FREE ACCESS TO LARGE SCALE DATA
RESOURCES.
YOU CAN PULLED CUSTOM COHORT
DATA SETS BASED ON YOUR
PARTICULAR INTEREST AND
PARTICIPANTS, BIO SPECIMENS AND
CLINICAL AND OMIC DATA AND
ENCOURAGING COLLABORATIONS
AMONGST THE INVESTIGATORS.
HERE'S THE WEBSITE.
AND COMING SOON, WE HAVE THE
EXPERIMENTAL MODELS OF DOWN
SYNDROME RESEARCHER PORTAL.
THIS IS A NEW RESOURCE.
IT'S DESIGN TO FACILITATE
SHARING AND ANALYSIS OF DATA
SETS GENERATE FROM EXPERIMENTAL
MODELS OF DOWN SYNDROME
INCLUDING ANIMAL MODELS AND
IPSCs.
THERE'LL BE NEW KEY FEATURES.
A STUDY FINDER.
THERE WILL BE AN INDEX OF
PUBLICATIONS FOR WHAT IS
INCLUDED IN THE PORTAL.
THERE'S AN EX PLORATION PORTAL
FOR ANIMAL MODELS AND FOR GENES,
PROTAENZ --
PROTEINS AND METABOLITES.
AND WE'RE INTERESTED IN THE
ANIMAL MODEL AND IT WILL GIVE
THE ABILITY TO LOOK AT WHICH
GENES ARE TRIPLICATED AND THEN A
LINK TO THE ORIGINAL
PUBLICATIONS.
THEN ANOTHER NEW TOOL WILL BE
THE EXPERIMENTAL MODELS DATA SET
EXPLORATION TOOL TO INTERACT
WITH DATA SETS FROM EXPERIMENTAL
MODELS BY EXPLORING GENES,
PROTEINS AND METABOLITES,
TISSUES, ORGANS AND CELL TYPES
AS I SAID EARLIER.
AND YOU'LL BE ABLE TO USE THIS
IN PORTAL ANALYSIS DASHBOARD TO
RAPIDLY VISUAL THE EFFECTS OF
TRYSOMY 21 AND ALLOWED CREATION
OF THE SHARED RESOURCES.
DEF
WE HAVE AN INFUSION OF YOUNGER
PEOPLE WHO SEE WORK UNDOWN
SYNDROME AS AN IMPORTANT AREA TO
FOCUS THEIR CAREER AND THE
INCLUDE INITIATIVE FUND THE DS3
THE DATA SCIENCE DIVERSE
SCHOLARS IN DOWN SYNDROME
RESEARCH.
INCLUDE DATA COORDINATION COURSE
IN DATA SCIENCE AND YOU CAN SEE
THAT 2023 SCHOLARS HERE IN
COLORADO.
AND THEY LEARN ABOUT THE BASICS
OF GENERATION IDENTIFICATION AND
COLLECTION OF HIGH CONTENT
MULTI-DIMENSIONAL DATA SETS AND
LEARN HOW TO WORK WITH THOSE
DATA SETS INCLUDE PAY FOR THEIR
TRAVEL, THEIR LODGING, AND GIVE
THEM A PER DIEM AND 11 TRAINEES
WERE SUPPORTED AND THERE'LL BE
ANOTHER COURSE IN 2025.
THERE'S THE QR CODE THERE.
THIS HAS BEEN TERRIFIC IN TERMS
AGAIN OF BRINGING TEAM INTO THE
FIELD, GIVING THEM THE TOOLS
THEY NEED TO SUCCEED.
AND THERE'S AN ENORMOUS AMOUNT
OF THAT CAN BE DONE IN THE DATA
HUB, FOR EXAMPLE.
NO IRB PROTOCOLS ARE NEEDED.
YOU DON'T NEED TO GET QUALIFIED
TO WORK WITH ANIMAL MODELS.
YOU CAN START ASKING QUESTIONS
AND TESTING HYPOTHESES RIGHT
NOW.
SO JUST BRIEFLY AS MELISSA SAID,
MY LABORATORY IS ONE OF THE FEW
ON CAMPUS SO WHAT YOU DON'T
REALIZE IS THIS IS LIKE AN
ENORMOUS COLLEGE CAMPUS AND IN
MANY BUILDINGS ARE WET LAB --
LABORATORIES AND THE HOSPITAL
WHICH IS AT THE CENTER OF THE
CAMPUS, ARE ALL DOING RESEARCH.
IN MY LABORATORY AT THE OPPOSITE
END OF THE CAMPUS WE'RE ONE OF
THE FEW LABORATORIES FOCUSSING
ON DOWN SYNDROME AND WE ARE
TAKING THE OPPORTUNITY OF THE
FACT THAT MANY PREGNANT PEOPLE
ARE TESTED FOR DOWN SYNDROME.
WE BELIEVE THIS IS AN
OPPORTUNITY TO ADVANCE THE
HEALTH OF THE FETUS AND PERHAPS
IMPROVED INDEPENDENT LIFE
SKILLS.
SO WE'RE TESTING USING ANIMAL
MODELS AND IPSCs.
THE VARIOUS COMPOUNDS THAT MIGHT
DO THIS SO WE HAVE AN IN VITRO
APOACH AS WELL AS AN IN VIVO
APPROACH AND TO GIVE A SENSE OF
MY PERSONAL COMMITMENT AND MY
LABORATORY IS EXCITED ABOUT
USING SOME OF THE RESOURCES
AVAILABLE THROUGH INCLUDE.
WE HAVE BEEN WORKING WITH FOUR
DIFFERENT MOUSE MODELS OF DOWN
SYNDROME AND THEY'RE CLEARLY
DIFFERENT FROM EACH OTHER WE
KNOW PHENOTYPICALLY HOW
DIFFERENT THEY ARE BUT MORE WE
CAN DO IN TERMS OF GENOMIC AND
TRANSCRIPTOMIC ANALYSES IN TERMS
OF COMPARING THEM.
MY LABORATORY IS NOT FUNDED
THROUGH INCLUDE.
IT'S PURELY EXTRAMURAL.
BECAUSE THE RESOURCES ARE
PUBLICALLY AVAILABLE, WE CAN USE
RESOURCES AS CAN ALL OF YOU.
SO IT'S AN INCREDIBLY EXCITING
TIME.
I WISH YOU ALL WELL WITH YOUR
RESEARCH AND WE LOOK FORWARD TO
PRESENTATIONS AND DISCUSSIONS.
I JUST WANT TO MENTION I
PROVIDED BRIEF SNAPSHOTS OF EACH
OF THE AIMS LOOKING FORWARD TO
HEAR MORE ABOUT YOUR SUCCESSES
AND CHALLENGES AND THEN ON THE
RIGHT HERE PLEASE KEEP IN MIND
THAT THE INCLUDE INITIATIVE HAS
CREATED NEW RESOURCES AND WE ARE
ALSO VERY FOCUSSED ON INCREASING
THE WORKFORCE OF PEOPLE WHO ARE
DEDICATED TO DOING RESEARCH IN
DOWN SYNDROME TO ADVANCE THE
HEALTH OF PEOPLE WITH DOWN
SYNDROME.
THANK YOU VERY MUCH.
>> THANK YOU VERY MUCH FOR YOUR
WELCOMING REMARKS AND INSIGHTFUL
COMMENTS ABOUT SOME OF THE DOWN
SYNDROME RESEARCH BEING
SUPPORTED THROUGH THE INCLUDE
PROJECT, DR. BIANCHI.
NOW IT'S MY PLEASURE TO
INTRODUCE MR. ISAIAH LOMBARDO
HE WORKS FULL TIME AT SHAKE SHAM
SHACK AND PARTICIPATED OVER THE
YEARS IN HORSEBACK RIDING,
BOXING, BASEBALL, BOWLING AND
BOSTON BALLET DANCE CLASS.
I'M EXHAUSTED THINKING ABOUT
THAT.
HE DANCES IN A CLASS WITH ADULTS
AND HAS A FACEBOOK PAGE CALLED
ISAIAH'S ADVENTURES AND LOVE
SPENDING TIME WITH HIS FRIENDS
AND FAMILY.
SO PLEASE JOIN ME IN WELCOMING
MR. ISAIAH LOMBARDO TO GIVE
PERSPECTIVES FROM A
SELF-ADVOCATE.
>> HI.
I WANT TO SAY THANK YOU FOR
INVITING ME HERE TO SPEAK TO
YOU.
I'M VERY EXCITED FOR THE
OPPORTUNITY.
I WANTED TO TELL A STORY TO GIVE
AN EXAMPLE OF HOW I'M HERE
TODAY.
BECAUSE OF RESEARCH I WAS DOWN
TWO MONTHS PREMATURE WEIGHING
ONLY TWO POUNDS AND I WAS BORN
WITH A DISEASE AND IT CAUSED MY
INTESTINES NOT TO POOP OUT OF ME
I WAS SICK AND THEY DAY BIOPSY
AND HAD AMAZING RESOURCES TO PUT
A KOL OF THE MY BAG ON ME --
COLOSTOMY BAG ON ME AND SOME
WITH THIS DISEASE PASSED AWAY
FROM THE DISEASE.
DUE TO RESEARCH SOME FIGURED OUT
WHAT CAUSED IT AND HOW TO TREAT
IT AND HOW TO HAVE BABIES LIKE
ME LIVE AND GROW WHILE HAVING
THIS DISEASE.
MY EXPERIENCE IS ONE EXAMPLE
THAT IMPROVED MY CARE AND PEOPLE
WITH DOWN SYNDROME AND NOW
BABIES BORN AFTER ME WILL HAVE
EVEN BETTER LIVES DUE TO WHAT
YOU HAVE BEEN WORKING ON TODAY.
THAT IS PRETTY COOL.
RESEARCH IS THE REASON THAT
INDIVIDUALS WITH DOWN SYNDROME
HAVE BETTER LIFE STYLES AND
BETTER LEARNING OPPORTUNITIES.
THERE'S A LOT OF RESEARCH AND
THERE'S INDIVIDUALS WITH DOWN
SYNDROME.
MY MOTHER TAUGHT ME TO USE MY
VOICE FROM A YOUNG AGE.
I LEARNED TO SPEAK UP FOR MYSELF
AND SHE SPOKE TO SCHOOLS AND
COLLEGE STUDENTS ABOUT RAISING
ME AND THEN I TOOK OVER AND NOW
I TALK TO THEM ABOUT MY LIFE
LIVING WITH DOWN SYNDROME AND
TALK TO SCHOOLS AND GENETIC
COUNSELING PROGRAMS AND COLLEGES
ABOUT MY LIFE.
BEFORE COVID I USED TO SPEAK TO
EVERY FOURTH GRADE CLASS TO TALK
TO KIDS ABOUT FRIENDSHIPS AND
DIFFERENCES IN HOW WE'RE MORE
THE SAME THAN DIFFERENT.
I LOVE SHARING MY STORY ABOUT
WHAT MY LIFE IS LIKE.
I LEARNED YOUNG THAT MY VOICE IS
IMPORTANT.
WHEN IT COMES TO MY INVOLVEMENT
IN RESEARCH IT'S ASSUMED.
IT'S IMPORTANT TO HAVE
CONFIDENCE AND TREAT PEOPLE AS
INDIVIDUALS.
AND I'M CURRENTLY DOING A
CLINICAL TRIAL IN COLORADO WITH
THE AMAZING DR. ESPINOZA AND I
WAS NERVOUS.
MY MOTHER WANTED ME TO DO IT AND
WAS NOT NERVOUS AT ALL AND I HAD
LOTS OF QUESTIONS AND HE TOOK
THE TIME TO ANSWER EVERY
QUESTION I HAD WHEN I SIGNED UP.
DURING THE SCREENING FOR THE
TRIAL THE RESOURCE TEAM ALSO
ADDRESSED ME AND TOLD ME EXACTLY
WHAT WAS HAPPENING.
YOU CAN SEE PICTURES OF ME IN
THE PROCESS.
AND THEY TALK TO ME AT EVERY
VISIT AND MAKE SURE I UNDERSTAND
WHAT IS HAPPENING AND ANSWERS
ALL MY QUESTIONS.
AND I'M AN ADULT NOW AND THE
WANT PEOPLE TO TALK TO ME AND
GOT MY QUESTIONS ANSWERS AND
IT'S A GREAT EXPERIENCE AND I
JOINED THE STUDY AND I COULD
HELP DR. ESPINOZA'S TEAM LEARN
MORE ABOUT THE MEDICATION AND
HOW IT WORKS.
I GET TO BE PART OF IT AND MY
SKIN IS GETTING BABY SOFT AGAIN.
IT'S ALSO IMPORTANT THE
QUESTIONS OF AREAS OF FOCUS COME
FROM THOSE WHO LIVE WITH DOWN
SYNDROME.
I HOPE WE TALK TO INDIVIDUALS
WITH DOWN SYNDROME TO HEAR THEIR
OPINIONS.
PEOPLE WITH THIS NEED TO BE PART
OF DEVELOPING RESOURCE QUESTIONS
I HOPE THE STUDY IN QUESTIONS
ARE GUIDED BY OUR FAMILIES AND
BY US.
WE HAVE LIVED EXPERIENCES ASKING
US WHAT WE WANT AND WHAT WE HOPE
FOR AND THERE ARE AREAS TO
IMPROVE IN.
I HOPE RESEARCH CONTINUES IN
AREAS SO HELP OUR LIVES IMPROVE.
MORE RESEARCH TO TEACH PEOPLE
HOW WE LEARN AND DEVELOP AND
MORE RESEARCH TO HELP CHILDREN
WHO HAVE BEHAVIORAL OR ANY
MEDICAL CONDITIONS.
MORE RESEARCH ON EMOTIONS AND
HOW IT HELP PEOPLE WITH DOWN
SYNDROME COPE AND HANDLE
DIFFICULT TIMES AND MORE
RESEARCH ON MEDICATIONS OR CARE
TO HELP US AND MORE RESEARCH TO
HELP SCHOOLS ADVOCATE US BETTER
AND EXPECT MORE FROM US.
I'M SURE WE ALL WANT THE PSALM
THINGS.
WE WANT PEOPLE WITH DOWN
SYNDROME TO HAVE THE HIGHEST
QUALITY OF LIFE.
HIGH EXPECTATIONS FOR LEARNING,
THE BEST MEDICAL CARE WE CAN GET
AND WE WANT TO BE ABLE IMPORTANT
MEMBERS OF OUR COMMUNITIES AND
IMPROVE HOW PEOPLE THINK ABOUT
HAVING DOWN SYNDROME AND WANT TO
WORK AND HAVE FRIENDS.
WE WANT TO FEEL IMPORTANT AND
ACCEPTED.
WE WANT TO LIVE LONG AND HAPPY
LIVES.
I HAVE A GREAT LIFE AND I'M
THANKFUL TO ALL THE DOCTORS AND
SCIENTISTS AND RESEARCHERS WHOSE
WORK GOES TO THAT AND I RECEIVED
AMAZING CARE AND I CAN DO BASIC
MATH AND IMPROVED AT READING
AND -- HOLD ON ONE SECOND, I'M
SO SORRY.
AND GOOD AT COMPUTERS AND I'M A
LIFE LONG LEARNER.
I WORK FULL TIME AT A JOB I LOVE
AND I STAY ACTIVE IN RECREATION
ACTION TESTS.
SO, IN CLOSING, I KNOW THAT
EVERYONE HERE IS EXCITED ABOUT
THE FUTURE AND WHAT WE CAN DO.
I HOPE YOU CAN GO HOME EVEN MORE
EXCITED AFTER ATTENDING THIS
CONFERENCE.
FOR THOSE WHO ARE NEW TO THE
WORLD OF DOWN SYNDROME, I SAY WE
ARE A GREAT GROUP OF PEOPLE TO
WORK WITH AND WORK WITH CHILDREN
AND THOSE WIN TOWN SYNDROME.
AND MY MOTHER ALWAYS SAID, AND
STILL SAYS, IF SOMETHING'S WRONG
AND I'M GRATEFUL IT MAKES ME WHO
I AM TODAY.
I AM EXCITED FOR ALL OF YOU TO
GET TO DO AMAZING RESEARCH.
THERE ARE SO MANY AREAS THAT
STILL NEED TO BE ADDRESSED AND
IT'S SO IMPORTANT FOR OUR
QUALITY OF LIFE.
YOU ARE MAKING SUCH A HUGE
DIFFERENCE FOR SO MANY PEOPLE.
YOU ARE MAKING LIFE BETTER FOR
THE PEOPLE WHO ARE ALIVE NOW
LIKE FOLKS MY AGE AND YOU'RE
PREPARING THE WORLD FOR THE
FUTURE BABIES WHO WILL BE BORN.
YOUR RESEARCH WILL IMPROVE THEIR
FUTURES COMPARED TO THOSE WHO
CAME MANY YEARS BEFORE ME.
THANK YOU FOR INVITING ME TO
TALK TO YOU TODAY.
I'M AROUND FOR ANY QUESTIONS IF
YOU SEE ME IN THE HALLWAYS, I
WANT TO THANK YOU FOR COMING TO
THIS CONFERENCE TO LEARN MORE
AND SO YOU GO HOME EMPOWERED AND
READY TO TACKLE IMPORTANT WORK
THAT NEEDS TO BE DONE TO HELP
FOLKS LIKE ME.
THANK YOU.
>> THANK YOU SO MUCH, ISAIAH.
I THINK WE'RE ALL INSPIRED BY
YOUR WORDS AND YOUR CHARGE
LEADING US IN THE CHARGE OF MORE
RESEARCH FOR PEOPLE WITH DOWN
SYNDROME.
THANK YOU.
NEXT I'D LIKE TO INTRODUCE A
CO-PRESENTER -- SOMEBODY DID
THAT FOR ME.
WOW.
OKAY.
SO DR. ANNA MAZUKO WILL GIVE THE
FIRST PART AND AIL GIVE THE
SECOND.
SHE'S A SENIOR ADVISER TO THE
NIH DEPUTY DIRECTOR FOR PROGRAM
COORDINATION, PLANNING AND
STRATEGIC INITIATIVES.
BEFORE JOINING DPCPSI SHE SERVED
AS THE ACTING DEP UTILITIED
DIRECTOR AND ADVISER FOR NIH
WIDE ACTIVITIESTOWN THE OFFICE
OF THE DIRECTOR HOLDING THE
LATTER POSITION SINCE 2022.
SHE'S BEEN WITH THE OFFICE OF
THE DIRECTOR FOR A NUMBER OF
YEARS AND WAS INVOLVED OF THE
STRATEGIC PLAN FOR DIVERSITY,
EQUITY, INCLUSION AND
ACCESSIBILITY AND SEARCHED AS
THE DEPUTY DIRECTOR OF THE NIH
HEAL INITIATIVE HELPING TO END
ADDITION LONG TERM.
SHE'S BEEN VERY INVOLVED IN THE
COORDINATION AND LAUNCH OF THE
INCLUDE INITIATIVE AND ONE OF MY
PARTNERS IN CRIME FOR THE
ACTIVITY AND A WOULD WELCOME
DR. MAZZUCCO TO TELL US ABOUT
THE FIVE YEARS OF
TRANSFORMATION.
>> THANK YOU.
IT'S MY PLEASURE GIVE THIS
PRESENTATION WITH MY DEAR
COLLEAGUE, MELISSA.
WE'VE BEEN PARTNERS IN CRIME
SINCE THE LAUNCH OF INCLUDE WITH
A TEAM OF FOLKS ACROSS NIH
WORKING TOGETHER ON DOWN
SYNDROME.
SO WE'D LIKE TO JUST TAKE THIS
MOMENT TO GIVE YOU JUST A LITTLE
HISTORY AS WE ENTER THE NEXT
PHASE OF INCLUDE AND THINK ABOUT
ITS FUTURE TOGETHER.
SO A LITTLE BACKGROUND ON WHAT
KIND OF STARTED ALL THIS WORK AS
MOST OF YOU KNOW, EACH YEAR
THERE'S ABOUT 6,000 BABIES IN
THE UNITED STATES BORN WITH DOWN
SYNDROME AFFECTING APPROXIMATELY
ONE IN EVERY 700 BABIES.
AND IN PARTICULAR BECAUSE OF
THAT RESULTED IN BETTER
TREATMENT FOR BABIES BORN WITH
DOWN SYNDROME THE AVERAGE LIFE
SPAN DOUBLED FROM 30 TO 60 YE
YEARS.
THEY'RE LIKELY TO ALZHEIMER'S
DISEASE WHILE BEING PROTECTED TO
FORMS OF CANCER.
FOR THIS REASON, AS THE AN
INCREASING NEED AS YOU ALL KNOW
FOR RESEARCH FOCUSSING ON
QUALITY OF LIFE NEEDS FOR
INDIVIDUALS WITH DOWN SYNDROME
ACROSS THEIR LIVES.
SO I WANT TO JUST TAKE A STEP
BACK AND TALK A LITTLE BIT ABOUT
NIH HISTORY AS WE'VE COME TO
LEARN MORE ABOUT DOWN SYNDROME
AND SEE THE RESEARCH GROW OVER
THE YEARS.
THIS IS A LITTLE BIT OF A
SNAPSHOT WHERE WE WERE SIX YEARS
AGO WHEN NIH LAUNCHED THE
INCLUDE PROJECT AND OUR TEAM,
MANY OF WHOM SUCH AS MELISSA
HAVE BEEN WORKING ON INCLUDE
SINCE IT BEGAN.
SO IN 2005, THE NICHD DEPUTY
DIRECTOR LAUNCHED THE FIRST NIH
WIDE DOWN SYNDROME WORKING GROUP
WHICH WAS COMPOSED OF SEVERAL
INSTITUTES FROM ACROSS NIH YOU
SEE LISTED HERE AND THE GROUP
WAS TASKED BY OUR PREVIOUS
DIRECTOR TO DEVELOP A RESEARCH
PLAN FOR DOWN SYNDROME IN FY2007
FOCUSSING ON COGNITION AND OTHER
HEALTH-RELATED ISSUES FOR DOWN
SYNDROME.
THIS IS THE HISTORY OF THE WORK
AT NIH AND WHERE WE STARTED WHEN
INCLUDE FIRST CAME INTO BEING.
YOU CAN SEE NIH HAD A DOWN
SYNDROME RESEARCH PLAN.
THE FIRST ON THE LEFT WAS
LAUNCHED IN OCTOBER 2007 AROUND
THE TIME THAT THE NIH DOWN
SYNDROME WORKING GROUP WAS
STARTED.
AND REALLY THE POINT HERE IS
THAT ACROSS THE YEAR THINKING
ABOUT DOWN SYNDROME RESEARCH AT
NIH WE WANTED TO TAKE A
THOUGHTFUL APPROACH AND
STRATEGIC APPROACH TO ENSURE WE
HAVE A COHESIVE FRAMEWORK FOR
THINKING ABOUT DOWN SYNDROME,
SETTING OUR RESEARCH PRIORITIES
AND MAKE SURE IT'S A
COLLABORATIVE EFFORT THAT BRINGS
TO BEAR ALL OF NIH'S STRENGTHS
AND EXPERTISE IN THIS AREA.
YOU CAN SEE IN THE MIDDLE WE HAD
ANOTHER RESEARCH PLAN IN 2017
AND THEN I'M PLEASED TO SHOW ON
THE RIGHT OUR MOST RECENT DOWN
SYNDROME RESEARCH PLAN WHICH
INCLUDES RESEARCH ACTIVITIES
RELEASED IN 2022.
I WANTED TO MENTION ONE THING
THAT WAS IMPORTANT TO US TO HAVE
PUBLIC INPUT INTO THE RESEARCH
MAN'S TO CAPTURE THE NEEDS OF
THE COMMUNITY AND THOUGHTS OF
RESEARCHERS.
THE 2022 PLAN IS AVAILABLE ON
OUR INCLUDE WEBSITE.
YOU CAN SEE THE LINK RIGHT
THERE.
AND I WANT TO MENTION OF COURSE
SOMETHING WE KNOW.
I THINK AS IS TRUE IN LIFE
GENERALLY, SOMETHING SO
IMPORTANT TO DO TOGETHER.
WE KNOW WE CAN'T DO THIS ALONE.
AND SO NIH HAS BEEN VERY PLEASED
TO TO CONTINUE TO WORK ON DOWN
SYNDROME WITH RESEARCHERS AND
ADVOCACY ORGANIZATIONS TO MAKE
SURE WE UNDERSTAND THE NEEDS OF
THE COMMUNITY AND THAT THEY ARE
REALLY INFORMING WHERE THE
SCIENCE GOES.
SO WE'RE VERY PLEASED THE DOWN
SYNDROME CONSORTIUM WHICH WAS
BEGUN IN 2011 REGULARLY MEETS
WITH 13 NIH INSTITUTES
PARTICIPATING, 17 PROFESSIONAL
ORGANIZATIONS, ADVOCACY GROUPS
AND FOUNDATIONS AND THREE
SELF-ADVOCATES.
YOU CAN SEE ALL THE MEMBERS
LISTED HERE AND THE CONSORTIUM
HAS PROVIDED CRITICAL INPUT INTO
THE DOWN SYNDROME RESEARCH PLANS
AS SHOWN ON THE PREVIOUS SLIDE.
AND THIS SLIDE, THIS ONE SPEAKS
FOR ITSELF, I THINK, BECAUSE
FRANK DID BETTER THAN ANY OF US
COULD IS BUT AS DR. BIANCHI
MENTIONED, IN 2017, IT WAS HIS
TESTIMONY ABOUT CONGRESS WHICH
GAVE US THE RESOURCES WE HAVE
TODAY AND IS WHY WE'RE REALLY
ALL HERE AND INCLUDE WAS ABLE TO
LAUNCH THE FOLLOWING FISCAL YEAR
IN 2018.
SO LASTLY AS YOU HEARD FROM
DR. BIANCHI WHEN WE RECEIVED THE
ADDITIONAL RESOURCES FROM
CONGRESS, THE DOWN SYNDROME
WORKING GROUP WHO HAD BEEN
WORKING TOGETHER ON DOWN
SYNDROME FROM CONGRESS AND WHAT
I HOPE YOU'LL HEAR AS THEMES FOR
TODAY AND TOMORROW'S
DISCUSSIONS, THE GOALS OF THE
INCLUDE PROJECT REALLY ARE TO
INVESTIGATE CONDITIONS THAT
AFFECT INDIVIDUALS WITH DOWN
SYNDROME AND THE GENERAL
POPULATION SUCH AS ALZHEIMER'S
DISEASE, AUTISM, CATARACTS,
CELIAC DISEASE AND CONGENITAL
HEART DISEASE AND DIABETES.
INCREASE THE NUMBER OF
INVESTIGATORS AND TRAINEES
STUDYING DOWN SYNDROME, ENGAGE
WITH THOSE WITH DOWN SYNDROME
AND THEIR FAMILIES FROM DIVERSE
BACKGROUNDS TO PARTICIPATE IN
ONGOING RESEARCH.
INCLUDE APPLIES EXPERTISE AND
RESOURCES FROM ACROSS 18 NIH
INSTITUTES AND CENTER TO
COLLABORATIVELY ADVANCE THE
CURRENT STATE OF DOWN SYNDROME
SCIENCE.
THE INCLUDE PROJECT IS DIVIDED
INTO THREE COMPONENTS INCLUDING
TARGETED HIGH RISK DISCOVERY
SCIENCE FOCUSSING ON THE BIOLOGY
OF CHROMOSOME 21, BUILDING A
LARGE COHORT OF INDIVIDUALS WITH
DOWN SYNDROME FOR COMPREHENSIVE
ANALYSIS AND BIOMARKER
EVALUATION AND INCLUDING
INDIVIDUALS WITH DOWN SYNDROME
AND EXISTING AND FUTURE COHORTS.
-- CLINICAL TRIALS.
I WANT TO JUST MENTION THIS
STARTED FROM ADDITIONAL
RESOURCES FROM CONGRESS AND AS
DR. BIANCHI SAID THE RESOURCES
HAVE CONTINUED TO GROW SO WE'RE
EXTREMELY GRATEFUL FOR THE
SUPPORT FROM CONGRESS AND OUR
COMMUNITY TO CONTINUE TO BUILD
THE RESEARCH AND SEE WHAT
STARTED OFF IN 2018 ONE $23
MILLION OF RESOURCES FROM
CONGRESS HAS GROWN TO WHERE WE
ARE IN 2023 WITH $90 MILLION IN
FUNDING SPECIFICALLY FOR THE
INCLUDE PROJECT.
AT THE NIH TO DATE OVER THE LAST
FIVE YEARS INCLUDE HAS INVESTED
$348 MILLION OVER THE PAST SIX
YEAR ON 330 PROJECTS FOR THE
INCLUDE INITIATIVE ALONE.
WE'VE RELEASED PROJECTS AND THE
MAJORITY OF INCLUDE FUNDS HAVE
SUPPORTED HIGH-RISK DISCOVERY
PROJECTS AND CLINICAL TRIALS AND
THE NUMBER OF CLINICAL STUDIES
AND CLINICAL TRIALS SUPPORTED BY
INCLUDE HAS INCREASED EVERY YEAR
OF THE PROGRAM.
SO LASTLY JUST A FEW MORE
SNAPSHOTS OF WHERE WE ARE BEFORE
I TURN IT OVER TO MELISSA, AS I
SAID, WE'VE NOW FUNDED 330
PROJECTS, 50 FUNDING
OPPORTUNITIES, ALMOST 250
PUBLICATIONS.
WE MAINTAIN 18 INSTITUTES AND
CENTERS ACROSS NIH COLLABORATING
ON INCLUDE.
13 CLINICAL TRIALS, A DATA
COORDINATING CENTER AND 13
INCLUDE HOSTED COMMUNITY
ENGAGEMENT AND OUTREACH EVENTS.
THANK YOU SO MUCH FOR COMING AND
NOW I'LL HAND IT OVER TO MY DEAR
COLLEAGUE, MELISSA, TO TALK MORE
ABOUT THE ACCOMPLISHMENTS OF
INCLUDE YOU HAVE GIVEN US TODAY.
THANK YOU VERY MUCH.
>> THANK YOU, ANNA.
I REALIZE I CAN'T DO ALL THE PJZ
JUSTICE SO IT WILL BE MORE LIKE
A TEASER AND THE PEOPLE WHO HAVE
DOING THE RESEARCH ARE GIVING
PRESENTATIONS TODAY AND TOMORROW
AND GET MORE A VIEW OF THE
ACCOMPLISHMENTS THUS FAR.
WE'RE STILL IN EARLY DAYS BUT
EXCITED ABOUT WHAT WE LEARN AND
LEARN.
THERE'S BEEN STUDIES THAT LOOKED
AT THE IMPACT OF COVID-19 ON
INDIVIDUALS WITH DOWN SYNDROME
ESPECIALLY THOSE WHO HAVE HAD
MORE SEVERE MANIFESTATIONS OF
THE CONDITION.
AS YOU HEARD FROM DR. BIANCHI
HOME SLEEP STUDIES COULD
REVOLUTIONIZE RESEARCH AND
THERE'S A WAY TO MEASURE VISUAL
ACUITY AND THE DOSAGE OF GENES
ON CHROMOSOME 21 AND HOW THEY
IMPACT THE FEATURES ON AN
INDIVIDUAL.
THERE'S BEEN WORKING AT
COGNITIVE MEASURES AND TRYING TO
USE THE NIH TOOL BOX AND OTHER
TOOLS TO BETTER UNDERSTAND
BEHAVIOR AND DEVELOPMENT IN DOWN
SYNDROME INCLUDING THE BEHAVIOR
INVENTORY OR BIDS THAT'S BEEN
DEVELOPED.
WE HAVE ALSO BEEN STUDIES MANY
OF THE GENES ASSOCIATED WITH
CONGENITAL HEART DISEASE IN
INFANTS BORN WITH DOWN SYNDROME
AND FUNDING ONGOING STUDIES
THROUGH THE ALZHEIMER'S
BIOMARKERS CONSORTIUM DOWN
SYNDROME PROJECT YOU HEARD A BIT
ABOUT FROM DR. BIANCHI WITH 92
INVESTIGATORS ACROSS 19
INSTITUTIONS AND SOME RESEARCH
FUNDED BY THE GROUP SHOWN IN THE
PICTURE STARTING TO SHED LIGHT
ON THE NEURAL PATHOLOGY AND
DISEASE PROGRESSION AND
THERAPIES SPECIFIC FOR DOWN
SYNDROME.
YOU KNOW YOU'LL HEAR MORE LATER
ON.
WITH REGARD TO DATA SUPPORT AND
DATA MANAGEMENT, WE'RE VERY
PLEASED WITH THE PROGRESS OF THE
INCLUDE DATA COORDINATING
CENTER, WHICH IS REALLY
DEVELOPING AN ECO SYSTEM TO
SUPPORT DOWN SYNDROME RELATED
RESEARCH.
IN MANY WAYS IT'S SERVING AS A
MODEL FOR WAYS TO PROMOTE DATA
ACQUISITION AND SHARING AND
REUSE ACROSS THE NIH BASED ON
FOCUSSING ON DOWN SYNDROME HAS A
STARTING POINT.
THE DCC IS SUPPORTING DATA
COLLECTED FROM DS CONNECT THE
DOWN SYNDROME REGISTRY.
IT'S SUPPORTING RESEARCH
COLLECTED THROUGH THE TYSOM
EXPLORE AND IT'S A USEFUL TOOL
TO LEARN ABOUT PUBLICATIONS AND
GRANTS FUNDED THROUGH INCLUDE
AND THE DATA HUB ITSELF IS THE
PORTAL THAT GIVES ACCESS TO THE
DATA AND THE DATA ARE FREELY
AVAILABLE WITH REGISTRATION FOR
THE PROEPT MORE SECURE ASPECTS
OF THE DATA.
AND AS YOU HEARD FROM
DR. BIANCHI IT WILL HELP US TRY
TO INTEGRATE HUMAN DATA WITH
DATA FROM MODELS, ANIMAL AND
CELLULAR MODELS AND TISSUE-BASED
MODELS.
WE'RE VERY EXCITE ABOUT ALL THIS
PROGRESS BEING MADE.
THE MULTI-DIMENSIONAL DATA SETS
AND A SAMPLING OF THE 11 STUDY
THAT HAVE THEIR DATA ENTERED IN
THE DCC AND OVER 9,000 RESEARCH
PARTICIPANTS AND OVER 7500 WITH
DOWN SYNDROME AND TRISOM21 AND
HAVE DOWN SYNDROME RELATED
RESEARCH.
THERE'S CLINICAL PROFILES AS
MENTIONED FROM ALL THE
PARTICIPANTS THE HUMAN
PARTICIPANTS AND THERE ARE OVER
4,000 GENOMES AND OVER 1700
TRANSCRIPTOMES AND OVER 470
PROTEOMES AND OVER 400
METABOLOMES.
FOR THOSE IN DATA SCIENCE, THIS
IS A TREASURE TROVE OF TEFRL AND
INFORMATION THAT WILL HELP US
UNDERSTAND IN GREATER DETAIL
WHAT IS ACTUALLY HAPPENING IN
DOWN SYNDROME FOR INDIVIDUALS
AND POTENTIAL THERAPEUTIC
TARGETS FOR HOW TO IMPROVE
QUALITY OF LIFE FOR PEOPLE WITH
DOWN SYNDROME.
STAY TUNED BECAUSE EPIGENOMES
AND IMMUNE MAPS AND WE'LL COVER
ALL THE OMES BY THE TIME WE'RE
DONE.
PIVOTING , I WANT TO HIGHLIGHT
THE IMPORTANT WORK IN THE
TRAINING SPACE FOR THE INCLUDE
PROJECT.
AS DR. BIANCHI MENTIONED WE WANT
TO INCREASE THE NUMBER OF JUNIOR
OR EARLY CAREER INVESTIGATORS
WHO CHOOSE A CAREER IN DOWN
SYNDROME RELATED RESEARCH.
THUS FAR UNDER INCLUDE RELATED
GRANTS AND AWARDS WE SUPPORTED
40 TRAINEES INCLUDING T-32 AND
PEDIATRIC HEART NETWORK FELLOWS
AND INDIVIDUAL F31, KO8 AND K33
AAWARDEES AND THE DOWN SYNDROME
LED BY THE UNIVERSITY OF
COLORADO AND MENTIONED BY
DR. BIANCHI HAS SO FAR SUPPORTED
36 TRAINEES.
IF YOU DO THE MATH, THAT'S OVER
76 TRAINEES AND EARLY CAREER
INVESTIGATORS WHO BENEFITTED
FROM INCLUDE SUPPORT AND WE'RE
LOOKING TO SEE THAT NUMBER GROW
AND SEE SOME OF THOSE TRAINEES
SUCCESSFULLY COMPETE WITH NEW
AWARDS AS INDEPENDENT
INVESTIGATORS.
WE WANTED TO ALSO MENTION DS
CONNECT THE DOWN SYNDROME
REGISTRY.
A RESOURCE START NICHD IN 2013.
TO PROVIDE SECURE AND
CONFIDENTIAL SURVEY THAT WOULD
COLLECT INFORMATION FROM
INDIVIDUALS WITH DOWN SYNDROME
AND OFTEN TIMES FAMILY MEMBERS
WILL HELP WITH INPUTTING THE
DATA.
IT'S ALL WEB BASED AND ON THE
CLOUD.
I'M PLEASED TO ANNOUNCE WE'RE IN
THE PROCESS OF RELAUNCHING THE
WEBSITE AND NEW IMPROVED VERSION
OF THE REGISTRY ON A PLATFORM
HOSTED BY THE UNIVERSITY OF
COLORADO BUT CONTINUE TO BE
SUPPORTED BY THE NIH AND BY THE
INCLUDE PROJECT.
THERE'S SCIENTIFIC PROFESSIONAL
LISTED AS POTENTIAL
PROFESSIONALS FOR FAMILIES WHO
REGISTER AN ACCOUNT AND WANT TO
KNOW IF THEY MAY BE ABLE TO FIND
A PARTICULAR HEALTH CARE
PROVIDER AND FINALLY THE DS
CONNECT REGISTRY HAS HELPED WITH
RECRUITMENT FOR OVER 100
RESEARCH PROJECT.
THE GOAL IS TO CONNECT
INDIVIDUALS WITH RESEARCH
THEY'RE INTERESTED IN, THEY
CHOOSE WHETHER OR NOT THEY WANT
TO PARTICIPATE IN ALL IN A
CONFIDENTIAL MANNER.
WE'RE GOING TO CONTINUE THAT
UNDER ITS NEW HOME.
COMMUNITY OUTREACH AND THIS IS A
ROAD MAP OF 2024 INTO EARLY
2025.
WE HAVE A LOT OF MEETINGS WE
ATTEND OFTEN TIMES WITH RESEARCH
PROJECTS FROM INCLUDE AND THE
INCLUDE DCC.
WE HAVE BEEN ATTENDING A VARIETY
OF PROFESSIONAL ORGANIZATIONS,
INTERNATIONAL ORGANIZATIONS AND
WE WILL HAVE A STRONG PRESENCE
AT THE TRISOM RESEARCH SOCIETY
HELD IN ROME IN JUNE AND
HOPEFULLY WILL SEE SOME OF YOU
THERE AS WELL.
DIVERSITY, EQUITY, INCLUSION AND
ACCOUNTABILITY ARE ALSO A KEY
COMPONENT OF THE INCLUDE
INITIATIVE.
AND REALLY FORM A CORNERSTONE OF
WHAT WE'RE TRYING TO DO BOTH
WITH REGARD TO RESEARCH
PARTICIPANTS AND ALSO WITH
REGARD TO INVESTIGATORS.
WE'VE BEEN TRYING HARD TO
ESTABLISH POSITIVE RELATIONSHIPS
WITH THE COMMUNITY.
WE HAVE HOSTED A NUMBER OF DEIA
WEBINARS THAT HAVE INFORMATION
AND SPEARHWE HAVE PARTICIPATED
MEETINGS FOR EARLY STAGE
INVESTIGATORS PARTICULARLY THOSE
WHO MAY BE FROM UNDER
REPRESENTED COMMUNITIES SUCH AS
THE SOCIETY FOR THE ADVANCEMENT
OF CHICANOS AND THE BIOMEDICAL
RESEARCH CONFERENCE AND WE MET
WITH A GROUP IN PUERTO RICO AND
LINDA GARCIA WHO IS NOT ABLE TO
BE WITH US HERE TODAY
PARTICIPATED IN A CONGRESS IN
COSTA RICA AND WE'RE EXCITED
WITH OUR INTERNATIONAL
PARTNERSHIPS AND EFFORTS TO
INCREASE DIVERSITY WITHIN THE
INCLUDE INITIATIVE.
SPEAKING OF DEIA WEBINARS, I
WANT TO ENCOURAGE EVERYBODY TO
SIGN UP FOR THE NEXT UPCOMING
WEBINAR MAY 30, 2024.
THIS IS FREE, OPEN TO EVERYBODY.
IT'S ALL VIRTUAL THROUGH THE NIH
VIDEOCAST AND THOSE DOING
RESEARCH INVOLVING INDIVIDUALS
WITH DID DOWN SYNDROME MAY FIND
THIS SOMETHING.
P CORI HAS A GREAT DEAL OF
EXPERIENCE IN PATIENT-FOCUSSED
RESEARCH ARE.
I'M WINDING DOWN BUT I WANTED TO
INTRODUCE TO YOU A NEW
INITIATIVE THAT IS PART OF
INCLUDE THAT WE'RE VERY EXCITED
ABOUT.
THE DOWN SYNDROME INCLUDE COHORT
DEVELOPMENT PROGRAM ALSO KNOWN
AS DSCDP.
THIS IS GOING TO BE A
PROSPECTIVE STUDY THAT IS
INVOLVING AND GATHERING A LARGE
COHOST PEOPLE WITH DOWN SYNDROME
TO UNDER GO COMPREHENSIVE DEEP
PHENOTYPING UNDER A COMMON
PROTOCOL.
WE'RE WE ARE IN THE PROCESS OF
COMPETING THE AND THESE ARE THE
YELLOW CIRCLES ON THE LEFT AND
WE'LL BE SXEHARING AND COLLECTI
THE DEMOGRAPHIC AND CLINICAL
DATA AND ALLOWING FOR DISCOVERY
AND VALIDATION OF POTENTIALLY
NEW BIOLOGICAL TARGETS.
AND THEN FINALLY WE WILL HAVE A
BIO SPECIMEN ACQUISITION AND
SHARING INITIATIVE WHICH IS THE
SQUARE DOWN BELOW BE COMPETED
THIS SUMMER AND A FEDERATED
EFFORT TO BRING TOGETHER BIO
SPECIMEN BANKING EFFORTS FOR THE
AUSPICES OF ONE ENTITY TO HELP
COLLECT THE SAMPLES FROM THE
LARGE COHORT DEVELOPMENT
PROGRAM.
AND ALL THESE PIECES WILL BE
INTEGRATED WITH THE INCLUDE DCC
SO THE DATA WILL BE HARMONIZED
AND AVAILABLE FOR BROAD DATA
SHARING.
SO STAY TUNED FOR MORE ABOUT
THIS AND WE'RE VERY EXCITED
ABOUT IT.
SO I JUST WANT TO CLOSE BY
THANKING OUR INCLUDE
INVESTIGATORS MEETING PLANNING
TEAM SOME OF WHOM ARE SITTING
DOWN HERE, SOME OF WHOM ARE
SCATTERED ELSEWHERE.
WE COULDN'T HAVE DONE THIS
WITHOUT YOU AND GRATEFUL FOR OUR
PARTNERS AND SPECIAL THANKS TO
ISAIAH AKBAR AND KEYLA FOR
SUPPORTING OUR EFFORTS.
THANK YOU DMOR JOINING US ON THE
LOVELY NIH CAMPUS AND PLEASE
ENGAGE IN ALL OF THE ACTIVITIES
YOU CAN AND WE HOPE YOU ENJOY
THE REST OF THE MEETING.
THANK YOU.
>> I'M CHARLENE TRAM I'M A
PROGRAM DIRECTOR AT THE
NATIONAL, HEART, LUNG, BLOOD.
SO USED TO ACRONYMS I FORGET THE
FULL NAME.
I'M A MEMBER OF THE INCLUDE DOWN
SYNDROME WORKING GROUP AND I AM
HERE TODAY BECAUSE I HAVE THE
PRIVILEGE OF BEING THE LEAD
MEMBER OF OUR WORKING GROUP FOR
THE BASIC SCIENCE COMPONENT OF
THE INCLUDE PROJECT.
NAEFRT PRIF
PART OF THE PRIVILEGES ARE TO
INTRODUCE THE SPEAKER FOR THE
NEXT WE'LL HEAR THREE TALKS AND
GET IN THE SCIENCE RIGHT NOW.
WE'LL HAVE THREE TALKS AND THEN
I'LL ASK THE THREE SPEAKERS TO
COME TO THE FRONT AND WE WILL
HAVE 15 MINUTES AVAILABLE FOR
QUESTIONS AND DISCUSSION.
AFTER THAT WE'LL HAVE A SHORT
BREAK AND THEN WE WILL CONTINUE
THE DISCUSSION OF PARTICULARLY
OF AVAILABLE MODEL SYSTEMS FOR
BASIC SCIENCE AND OTHER
SCIENTIFIC ASPECTS.
WE'LL HAVE ANOTHER PANEL I'LL
TELL YOU ABOUT AFTER THE BREAK
AND START WITH SCIENTIFIC TALKS
AND THEN GET A CHANCE TO TALK A
LITTLE BIT MORE ABOUT THE
SPECIFIC CHALLENGES THAT COME
WITH BASIC SCIENCE AND STUDYING
DOWN SYNDROME.
OUR FIRST SPEAKER IS MICHAEL
YEAGER.
THE THEME OF THE FIRST SESSION
IS USE OF A VARIETY OF
EXPERIMENTAL MODELS.
WE'LL INDICATE HOW MUCH TIME IS
LEFT.
WE HAVE LIGHTS BUT CAN'T MAKE
THEM WORK.
>> THANK YOU FOR THE
INTRODUCTION AND I THINK WE'RE
OFF TO A GREAT START.
I JUST WANT TO SAY THANKS TO THE
ORGANIZA
ORGANIZERS AND THE CHANCE TO
TALK ABOUT WHAT OUR LAB IS
DOING.
FOR SEVERAL YEARS NOW AND IT'S A
LITTLE BIT DIFFERENT THAN THE
THRUSTS OF WHAT YOU MIGHT HEAR
THROUGHOUT THE MORNING IN TERMS
OF DATA SCIENCE WE'RE MORE
PATHOPHYSIOLOGISTS.
I WANT TO MAKE A PLUG FOR THAT
TOO AS WE GO.
WITHOUT FURTHER ADO, I HAVE NO
CONFLICTS OF INTEREST TO DECLARE
AND I ALWAYS LIKE TO HAVE A FEW
LEARNING OBJECTIVES.
I WON'T READ TO YOU, I PROMISE.
HOPEFULLY AFTER THIS 10, 15
MINUTES YOU'LL HEAR MORE THAN
YOU KNEW BEFORE ABOUT CARDIO
PULMONARY DISEASE.
MY BACKGROUND AND TRAINING IS IN
PULMONARY HYPERTENSION AND WANT
YOU TO BE MORE FAMILIAR WITH THE
BIOLOGICAL MECHANISMS WE THINK
ARE INVOLVED IN INCREASING
SUSCEPTIBILITY FOR PERSONS TO
RESPIRATORY INFECTION AND THEN
GO INTO NEW AVENUES TO WHAT
WE'VE BEEN DOING.
AS WE HEARD THE GOAL IS TO
IMPROVE THE QUALITY OF LIFE AND
AGREE WITH OUR ESTEEMED FIRST
SPEAKER.
THERE'S MANY DATA SETS.
WE ONLY HAVE 15 MINUTES SO I
PICKED A FEW.
THIS IS FROM YANG ET AL. ABOUT
20 YEARS AGO BUT FOLLOWED UP IN
SEVERAL STUDIES.
I PUT AN ARROW IN CASE LASERS
DON'T WORK BUT IF YOU THINK
ABOUT HIGH LUNG MORBIDITY AND
MORTALITY, WHAT ARE THE NUMBERS
THAT BACK THIS UP?
AS A PLUG, THIS IS SOMETHING
WE'VE BEEN WORKING ON ABOUT FIVE
YEARS.
NO OFFENSE TO THE EARLIER
SPEAKERS BUT ALWAYS IN THE LIST
OF THINGS THAT ARE PROBLEMS FOR
PEOPLE WITH DOWN SYNDROME IT'S
ALWAYS ALZHEIMER'S, LEUKEMIA AND
THEY'RE PROTECT FROM OTHER
THINGS.
IN THE NEXT SLIDES I'LL TRY TO
CONVINCE THE MAJOR PROBLEM FOR A
MAJOR PROBLEM IS RESPIRATORY
TRACT INFECTION.
AND I PUT A PLUG FOR CONGENITAL
HEART DEFECTS BUT YOU LOOK AT
THIS AND IT'S A DIFFERENT WAY TO
REPRESENTATIVE THE DATA.
IF YOU LOOK AT ASPIRATION OR
INFLUENZA AND PNEUMONIA AND GO
ACROSS THE LIFE SPAN AND I'VE
HIGHLIGHTED THIS FOR YOU, AT THE
DECADES IN WHICH YOU'D EXPECT
HIGH LEVELS OF DEMENTIA, THE
DOMINANT COMORBIDITY HERE IS
RESPIRATORY TRACT INFECT.
-- INFECTION.
I WOULD BE REMISS IF I WERE HERE
AND WE DIDN'T TALK A LITTLE BIT
ABOUT SARS, COV2, COVID-19 AND
ALL REPRESENTATIONS OF THE SAME
IDEA.
THIS FROM THE COVID-19
INITIATIVE PUBLISHED BACK IN
2021.
AND WHAT YOU CAN SEE IS IN
PURPLE INDIVIDUALS WITH DOWN
SYNDROME ARE MORE SUSCEPTIBLE TO
DEATH FROM SARS COV2.
I PUT SOME LISTS ON HERE ABOUT
SOME OTHER THINGS MIGHT THINK
ABOUT.
WHAT I'D LIKE TO SAY ABOUT THIS
THOUGH AS A LUNG RESEARCHER FOR
A LONG TIME THE COVID BLOCK OF
DATA FROM 2020 TO NOW IS VERY
MURKY.
AND AS THE PEOPLE WHO JUMPED IN
THE SPACE AND DID QUICK STUDIES
AND THE DATA IS DIFFICULT TO
WORK THROUGH.
FOR EXAMPLE, WHO DIED IN
COVID-19 VERSUS WHO DIED WITH
COVID-19 AND THIS IS A BIG
PROBLEM FOR US IN THE LUNG
COMMUNITY RIGHT NOW.
FOR EXAMPLE, IT'S UNKNOWN
SPECIFIC FACTORS, OBESITY AND
OTHERS WERE AS CONTRIBUTORY OR
MORE CONTRIBUTORY THAN THE
CONDITION OF HAVING DOWN
SYNDROME.
I WAS INVITED TO TALK ABOUT THE
NEWER STUFF WE'VE BEEN DOING IN
THE MOUSE AND RAT MODELS.
WE MADE AN ARNO 20 AND WE'LL
PUBLISH OUR FIRST DATA IN ARNO
20 IN A MONTH AND THESE ARE
SEQUENTIAL DUPLICATION AND WHERE
SEGMENTS OF HSA21 ARE
DUPLICATED.
THERE'S IMPORTANT
CONSIDERATIONS.
THERE'S OTHER DIFFERENCES BUT
YOU GET OVERSUPPRESSION OF THE
GENES ON 16, 17 OR 10 DEPENDING
ON WHICH MOUSE YOU DO.
WE TOOK THE SAME APPROACH TO
MAKE ARNO 11 AND 20 AND WERE
SUCCESSFUL.
I WON'T TALK ABOUT THESE TODAY
BUT I'LL BE AROUND AND SHOW WHAT
YOU WE HAVE AVAILABLE FOR YOU
AND HAVE THE LIST OF GENES.
INVOLVED IN THIS CASE, RATS ARE
SIMPLER.
IT'S SPREAD ON TWO CHROMOSOMES
NOT THREE AND LESS INDIVIDUAL
RAT GENES DUPLICATED NOT PRESENT
IN HUMAN.
THERE'S LESS OF THAT.
SO WE THINK THAT IN CONJUNCTION
WITH THE IDEA THAT RATS ARE
GENERALLY BETTER AT BEHAVIORAL
STUDIES AND THEIR STRUCTURE
LARGER.
FOR US TO LOOK AT HEART AND LUNG
ARE EASIER.
THIS SIDE IS BODY WEIGHT AND ALL
THIS ON THE DP16 MICE BUT WANT
TO FOCUS YOUR ATTENTION HERE.
THIS AT 11 WEEKS A COHORT OF
MICE WE LOOKED AT IN TERMS OF
HOW WE ANESTHETIZE THEM TO DO
THE THINGS WE DO.
IT TURNS OUT THERE'S BROAD
VARIABILITY IN THE DP16 MOUSE TO
GET THEM TO COME DOWN TO WORK
WITH THEM AND I KNOW SOME HERE
ARE INTERESTED IN RESPONSE TO
ANESTHESIA AND IF YOU GET THEM
UNDER AND DO DIFFERENT THINGS,
ONE THING WE LOOKED AT WAS
MOLECULAR ANALYSIS.
WHAT WE FIND IS BROAD
VARIABILITY IN INTERFERON
RECEPTOR EXPRESSION.
THIS IS ACROSS THE BOARD.
WE LOOKED AT THIS IN MANY WAYS.
WE USED FIVE DIFFERENT
ANTIBODIES AND ASKED OTHER
PEOPLE FOR THEIR PROTEINS.
WE PUT THEM ON TE GELS AND THIS
IS CONSISTENT.
THE CONSISTENT, INCONSISTENTLY
PARALLELS WHAT WE HEARD FROM
ISAIAH THIS MORNING, THESE ARE
INDIVIDUALISTIC DP16 MICE IN
TERMS OF THE EXPRESSION.
THE EXPRESSION IS QUITE
VARIABLE.
WE DON'T SEE AT THE PROTEIN
LEVEL OVEREXPRESSERS AND DIDN'T
SEE DIFFERENCE IN PATH RECEPTOR
WHICH FACILITATED BACTERIAL
ADHESION AND YOU CAN SEE WHERE
I'M GOING WITH THAT.
SO TO CONCLUDE ON THIS SLIDE, AT
LEAST A PROTEIN LEVEL INTERFERON
DOESN'T SEEM TO BE PRESENT IN
THE MOUSE LUNG.
NOT TO SAY THERE'S NOT AN FE
FEARONOPFEARON
-- INTERFERONOPATHY AND THE
LUNG APPEARS TO ABBE
ACCOMMODATING THIS IN SOME WAY
AND WE HAVE QUANTITATIVE DATA
AND SOMETHING LIKE USP18 IF
YOU'RE INTERESTED IN INTERFERONS
GENERALLY COMES UP AS A RESPONSE
TO INTERFERON ENGAGEMENT AND
TENDS TO ATTENUATE THE SIGNAL.
WE DEFINITELY SEE THAT AND IT'S
BEEN SHOWN IN MANY PUBLICATIONS
GOING BACK 20 YEARS IN WHICH
THERE'S A SHORT TERM, MEDIUM YUM
AND LONG-TERM ACCOMMODATION THE
SYSTEM SEEMS TO ESTABLISH.
WHAT WE'RE PROPOSING WITH THE
MODEL IS THERE'S AN
INTERFEROPATHY AND PROBABLY ONE
AT THE EARLY LEVEL BUT IT
ATTEMPTS TO TURN THIS DOWN AT
THE PROTEIN LEVEL.
AGAIN, WE LIKE OMICS BUT WE'RE
PATHOPHYSIOLOGISTS AT HEART.
THIS IS JUST TO SHOW YOU BY
DIFFERENT MEASURES CONDUCTED AT
DIFFERENT PRESSURES THAT THE
ELASTIN OF THE LUNGS, HOW STIFF
IT, ALSO OF THE AIRWAYS, HOW ARE
THEY WORKING TO BRING IN AIR AND
SOMETHING CALLED INSPIRATORY
CAPACITY YOU CAN BREATH NORMAL
AND THE TIDAL VOLUME AND THE
RESERVE YOU CAN DRAW IN IS
RESPIRATORY CAPACITY.
WE SAW DIFFERENCES IN GENERALLY
THE LUNG IS NOT VENTILATING
PROPERLY.
IN ADDITION, AND WE FOUND IN
MICE THE INCREASED SIZE OF WHAT
WE CALL THE MEAN LANEIAR
INTERCEMENT WHERE WE LOOK AT
ALVEOLI AND THIS IS EQUIVALENT
TO AN EMPHYSEMA AND FINALLY MORE
TOWARDS THIS AREA WE FIND
PROMINENT LYMPHOID TISSUES THAT
CONTROL LOCAL LUNG IMMUNITY.
TO SUMMARIZE, THERE'S CLINICALLY
MEANINGFUL LUNG CAPACITY IN MICE
THAT MAY BE LINKED TO INCREASES
IN THE STRUCTURAL DIFFERENCES
AND SOME OF THOSE STRUCTURAL
DIFFERENCE IMMUNOLOGICAL GUIDES
THE LUNG USES WE THINK ARE
PROBABLY DIFFERENT IN PEOPLE
WITH DOWN SYNDROME.
IF WE GO TO HEARTS REAL QUICK I
HAVE THREE MINUTES.
THESE ARE MEASURES HOW THE RIGHT
VENTRICLE IS DOING WHEN WE HAVE
SEPTAL DEFECTS BETWEEN THE RIGHT
AND LEFT VENTRICLE AND LOOK AT
CARDIO GRAPHY AND INVASIVE CATH
AND LOOK IF THERE'S
COMMUNICATION AND LOOK AT IF
THERE'S INCREASED FLUID ON THE
RIGHT VENTRICLE OR GROWS IN SIZE
AS YOU EXPECT A MUSCLE HAVING TO
WORK HARDER DOES.
DON'T SEE ANY REAL CHANGE
THERE'S.
ALSO DIDN'T SEE OVER EXPRESSION
OF INTERFERON RECEPTORS.
BUT IMPORTANTLY, WHEN WE GET TO
THE PATHOPHYSIOLOGY THIS NUMBER
THE MEAN PRESSURE IS IMPORTANT.
IT'S NORMALLY ABOUT 15 AND IT IS
15 IN CONTROLS IN DP16 AND THIS
SUGGESTS IN DP16 MICE AND THIS
IS 10 FEMALES AND 10 MALES AND
WE HAVE THE SAME DATA FOR ECHO
CA
CAR
CARDIOGRAPHY AND IN WERE
DIFFERENCES IT WOULD BE HIGHER.
THAT'S SUMMARIZED HERE.
WE HAVE TO GET TO THE ANSWER
HERE BECAUSE CHD AND 16 MICE THE
INITIAL REPORTS WERE 33 TO 22%
AND THERE'S BEEN REPORTS WHERE
TWO-THIRDS OF ANIMALS ARE HAVING
THIS AND OUR DATA DOESN'T SHOW
CLINICAL OR MEANINGFUL BY ECHO
AND CATH AND NOT MUCH OVER
EXPRESSION AT THE PROTEIN LEVEL.
THIS IS WHAT PNEUMONIA LOOKS
LIKE IN DP16.
IT'S HORRIBLE.
AND WHAT IT LOOKS LIKE IN
CONTROLS.
VERY DIFFERENT.
WE DON'T SEE EFFECTS LIKE
ENDOCARDITIS.
IN AREAS NOT CONSOLIDATED AND
HEAVILY CONSOLIDATED WITH
PNEUMONIA YOU SEE THE LYMPHOID
TISSUES MORE PARENT.
WE PUBLISHED -- MORE A PAIR ADID
APP
APPARENT AND MY BOSS ALWAYS TOLD
ME IF YOU GET TWO THINGS ACROSS
YO
YOU'RE YOUR NAME, MY NAME IS
MICHAEL YEAGER AND INFECTION
WITH A VARIETY OF BUGS IN THE
LUNG RELEASES LUNG TAU WHEN GOES
TO THE BRAIN AND REDUCES
COGNITION.
OUR STUDY WASN'T POWERED TO SEE
IT IN THE BRAIN BECAUSE WE
DIDN'T COLLECT BRAINS THAIN THA
WAY BUT IN THE HEART, LUNG AND
PLASMA OF CONTROLS ANIMALS WE
WEREN'T EMPOWERED BUT WE SEE
RELEASE OF LUNG TAU.
AND SO WHAT THIS SUGGESTS AND I
DON'T READ TAKE-HOME MESSAGES
I'LL SKIP TO THE END BECAUSE I
ALREADY HIGHLIGHTED THIS.
THIS RAISES THIS INTRIGUING
POSSIBILITY THAT RECURRENT LUNG
INFECTION AND DOWN SYNDROME
COULD CONTRIBUTE TO DECREASED
COGNITION.
MANY STUDIES SHOW IN RECURRENT
RESPIRATORY TRACT INFECTION WITH
PEOPLE WITH DOWN SYNDROME THEY
ALL SCORE LOWER IN COGNITIVE
ASSAYS.
THERE'S A STUDY FROM DENMARK
ABOUT 10 YEARS AGO THAT SHOWS
THIS.
THE OTHER THING I'D LIKE TO
POINT OUT, I DIDN'T HAVE TIME TO
TALK ABOUT THE ARNO RAT MODELS
BUT WE WERE CLEVER I THOUGHT AND
MADE THOSE IN TWO DIFFERENT
STRAINS.
WE SEE STRAIN DIFFERENCE IN THE
RATS.
I'D LIKE TO TO POINT OUT
ANYTHING DIFFERENCES OBSERVED IN
THE DP16 MICE MAY BE DEPENDENT
TOO.
THE MESSAGE WE GOT FROM OUR
GREAT FIRST SPEAKER IS THERE'S A
LOT OF INDIVIDUALISM IN DOWN
SYNDROME.
I'D LIKE TO THANK MY TEAM, AND
ESPECIALLY KELLY CALDWIN AND MY
SISTER, AMY AND HOW TO EVERYBODY
WHO DOES THIS AND ALL OUR
FUNDERS.
THANK YOU.
>> IF YOU HAVE QUESTIONS FOR HIM
YOU'LL GET TO ASK QUESTIONS AT
THE END OF THE PRESENTATIONS.
OUR NEXT SPEAKER IS DR. JENNIFER
LAWRENCE.
>> TO CONTINUE TO LOOKING AT THE
SCIENTIFIC QUESTIONS RELATED TO
DOWN SYNDROME.
DR. LAWRENCE.
>> THANK YOU.
I DO WANT TO THANK THE INCLUDE
ORGANIZERS FOR INVITING ME AND
FOR THEIR WHOLE GROWTH AND
SUPPORT IN THIS AREA OF RESEARCH
WHICH HAS BEEN PHENOMENAL.
I'M GOING TO TALK TO YOU TODAY
ABOUT KIND OF A VERY DIFFERENT
TYPE OF APPROACH THAN A LOT OF
STUDIES IN DOWN SYNDROME BUT ONE
THAT I HOPE IN DISCUSSION WE'LL
HAVE TIME TO TALK ABOUT COULD BE
COULD BE MAYBE EMPLOYED MORE AND
MY GROUP WILL BE HAPPY TO HELP
PEOPLE WHO MIGHT WANT TO
INTRODUCE THIS INTO THEIR OWN
RESEARCH.
WE'RE TRYING TO USE FUNDAMENTAL
EPIGENETIC MECHANISM OF EXIST
RNA WHICH SILENCING ONE X
CHROMOSOME IN FEMALES.
WE'RE TRYING TO TAKE THAT AND
APPLY IT TO TRISOMY 21 AND GROW
THE IDEA IT'S BROADLY APPLICABLE
TO CHROMOSOMAL IMBALANCES.
WE BASICALLY SHOWED THAT WAS THE
CASE AND EVERYTHING I'M GOING TO
SHOW YOU IS FUNDED THROUGH THE
INCLUDE OR NICHD NOW.
THIS WAS ORIGINALLY SUPPORTED BY
AN EUREKA GRANT FROM THE NIGMS.
SO THIS IS THE RNA CODING ONE OF
THREE CHROMOSOMES 21 AND IT
SILENCING IT AND IF YOU CAN
SILENCE AND IF YOU CAN SILENCE
IT FROM AN INDIVIDUAL WITH DOWN
SYNDROME WHAT CAN YOU DO WITH
THAT?
AND THIS IS DESCRIBED IN AN
ARTICLE AND OUR FIRST THING IS
WE'RE TRYING TO USE THIS AS AN
EXPERIMENTAL SYSTEM TO
MANIPULATE CHROMOSOME 21 AND
UNDERSTAND THE ROOT CAUSES OF
PHENOTYPES AND ALSO HAS A
REVOLUTIONARY POTENTIAL THAT CAN
BE DEVELOPED INTO A THERAPEUTIC.
OR CELLS THAT ARE BASICALLY
CHROMOSOME SILENCED OUTSIDE THE
BODY COULD BE INTRODUCED AS A
THERAPEUTIC.
I WANT TO SAY A LITTLE BIT ABOUT
WHY AN INDUCIBLE SYSTEM IS HAS
ADVANTAGES OVER CELL LINES EVEN
IF THEY'RE ISO GENIC.
I'M AN EPIGENETICISTS AND I'VE
KNOWN THE CELLS CHANGE IN
CULTURE.
AND SO THERE'S DIFFERENCES AND
WHAT IS DUE TO OVEREXPRESSION OF
CHROMOSOME 21.
I APPRECIATE THE PRIOR TALK BY
DR. YEAGER TALKING ABOUT VARIANT
-- VARIABILITY AND JUST TALK
ABOUT CHROMOSOME 21 AND THE
PAPER DISCUSSES ORGANOIDS AND
THE APPLICATION OF THAT TO
DIFFERENT CELL LINES AND YOU CAN
LOOK AT THAT.
SO WE'RE LOOKING FOR MORE DIRECT
INFECTS AND INDUCIBILITY ALLOWS
YOU TO INDUCE THE CORRECTION
LATER IN DEVELOPMENT TO SEE WHAT
THE EFFECTS ARE OF THAT.
IT ALLOWS YOU TO LOOK AT
DEVELOPMENTAL TIMING.
AND THE FIRST THING WE DID WAS
SAY, OKAY, IF YOU CAN SILENCE
ONE CHROMOSOME 21, DOES THAT
CORRECT THE CELL FUNCTION IN
DEVELOPMENT.
IN ORDER TO ADDRESS THAT WE DID
IT IN THE HEMATOPOINT --
HEMATOPOIETIC SYSTEM AND IT
FORMS A NEURON.
THIS WAS SHOWN IN MULTIPLE WAYS
IN THIS PAPER.
THIS PAPER ALSO SHOWED YOU CAN
INTRODUCE SILENCING LATER IN
DEVELOPMENT WHICH WAS NOT KNOWN
AT THE TIME AND WE THOUGHT TO
NOT BE THE WAY IT WAS.
AND ANOTHER STUDENT IF THE LAB
STUDIED WHAT HAPPENS AND IT LED
HER TO ANGIOGENESIS AND THE
PREVIOUS TALKED ABOUT
HYPERTENSION AND WE THOUGHT THE
ANGIOGENIC PHENOTYPE WAS NOT
NECESSARY AND WE WERE DOING
TABLEAU ROSA WHICH WE SEE.
WE DETECTED THIS.
SO AND THIS WAS PUBLISHED AND I
WAS TRANSITIONED TO THINGS THAT
AREN'T.
SO THE GENE PATHWAYS THAT WE SAW
AFFECTED ARE SHOWN HERE.
AND THE TWO CELL TYPES AFFECTED
ARE THESE.
I WANT TO POINT OUT THAT IN ALL
OF OUR DATA NOT SIGNALLING SEEMS
TO BE INCREASED IN THE TRISOMIC
CELLS AND WHEN WE SILENCE THE
CHROMOSOME IT DECREASED.
IF WE SILENCE THE ANGIOGENIC
RESPONSE IN FORMATION OF
MICROVESSELS GOES UP AND
NON-SIGNALLING GOES DOWN.
NOW I'LL SORT OF GIVE YOU A
TASTE OF THREE DIFFERENT NOVEL
EXTENSIONS OF THIS APPROACH.
WE'RE CURRENTLY WORKING ON THAT
ARE UNPUBLISHED.
FIRST, IS TO IDENTIFY A MINI
GENE, A SMALL GENE THAT SILENCES
PART OF CHROMOSOME 21.
THE OTHER IS TO I WANT TO
MENTION WE THINK THIS APPROACH
COULD CONTRIBUTE TO THE STUDY OF
POLYMORPHISMS BY SELECTIVELY
SILENCING DIFFERENT HOMO LOGS
AND WE'RE WORKING ON PUTTING
THIS INTO A MOUSE.
WE CREATED A MOUSE WITH SOME OF
THIS.
SO THE GOAL OF THIS WAS TO
REDUCE THE SIZE EXIST 14RNA AND
IF YOU WANT TO USE IT
THERAPEUTICALLY IT CAN'T BE USED
IN THAT FORM AND WE MADE A MINI
GENE OUT OF THE REPEAT AND
MAKING OTHER MINI GENES WITH
OTHER MROPROPERTIES AND WHAT YO
SEE IS THE MINI GENE RNA DIDN'T
COAT THE CHROMOSOME.
BOTTOM LINE IT LOCALIZE TO THE
DOWN SYNDROME CRITICAL REGION
BECAUSE WE INSERTED IT AND IN
THE DOESN'T INCREASE THE UNLESS
WE INCREASE THE RNA.
WHAT WE'RE DOING IS STUDIES THE
EFFECTS OF THAT MINI GENE ON
OTHER -- OTHER GENES AND HERE
IT'S REPRESSED AND OTHER GENES
NEAR IT WERE REPRESSED AND WE
WERE TRYING TO MAKE THE MINI
GENES AND WE'RE CURRENTLY
WORKING ON RNA SEQ AND ERIC
LARSON IN MY LAB IS LEADING
THAT.
THIS IS JUST AN EXAMPLE OF THIS
IS THE REGION WITH THE WHOLE
CHROMOSOME AND THIS IS JUST THE
MINI GENE.
YOU SEE THAT IT'S EFFECTING A
REGION WE THINK IS AROUND 2 TO 5
MEGA BASIS.
TO SHOW EXAMPLES OF WHAT THE
DATA LOOKS LIKE, THIS ISO GENIC
IS A CONTROL.
IF WE PUT DOCKS ON THE CELLS IT
HAS A LITTLE AFFECT BUT WE HAVE
TO DO THAT BECAUSE IT DOES
AFFECT SOME GENES.
HERE'S THE APP GENE FAR AWAY
FROM THE DOWN SYNDROME CRITICAL
REGION AND WHEN WE DO A
FULL-LENGTH SILENCING, OR MINI
GENE IT DOESN'T.
AND HERE'S A DIFFERENT GENE.
THIS IS DSCR3 AND THAT'S
REPRESSED BECAUSE IT'S IN THE
REGION.
THESE ARE COMPARING OTHER GENES
AND THIS GOES DOWN WITH OTHER
MINI GENES AND THIS ONE GOES
DOWN MORE MODESTLY 1.5 MEGA
BASES AND THIS ONE DOESN'T GO
DOWN AT ALL.
THERE MAY BE SOME THAT DON'T GO
DOWN IN THE REGION.
NOW WE'RE USING THIS APPROACH TO
SAY HOW DOES REPRESSION OF JUST
GENES IN THE DSCR REGION IMPACT
GENOME-WIDE PATHWAYS?
I'LL SHOW A FEW EXAMPLES.
SO SOME CHROMOSOME 21 GENES IF
WE SILENCE JUST THAT REGION IT
LOOKS SIMILAR TO THE DATA IF YOU
SILENCE THE WHOLE CHROMOSOME.
HERE'S FULL CHROMOSOME AND TWO
MINI GENES.
AS I MENTIONED, NOT SIGNALLING
IS A THEME THAT KEEPS COMING UP
IN OUR WORK.
THIS GENE'S IMPORTANT IN NOT
SIGNALLING.
THIS IS OUR CONTROL FOR THE
DOCKS AFFECTS OTHERS WILL REDUCE
IN THE MINI GENES BUT NOT AS
FULLY AS THE FULL LENGTH.
THIS APPROACH IN ALL THESE GENES
ARE INVOLVED IN NOT.
WE FIND SURPRISINGLY A FEW
NON-CHROMOSOME 21 GENES DECREASE
MORE IF YOU SILENCE JUST THAT
PART OF THE CHROMOSOME THAN IF
YOU SILENCE THESE ARE OF THE
CHROMOSOME 21 GENES AND THIS MAY
REFLECT DISRUPTION OF THE
BALANCE OF GENES ON CHROMOSOME
21.
NOW WE'VE -- THEY'RE NOT AN
EQUAL DOSAGE ANYMORE.
OKAY.
SO YOU CAN THEN APPLY THIS
APPROACH TO DIFFERENT PATHWAYS
TO SAY WHAT PATHWAYS ARE
AFFECTED IF WE REPRESS THE WHOLE
CHROMOSOME VERSUS THE TWO MINI
GENES.
YOU CAN SEE CARDIAC SEPTUM
COUPLES AND ANGIOGENESIS COMES
UP AND INTERESTING RIBOSOME ARE
FAR FROM OUR MINI GENE.
I WANT TO MENTION THE IDEA -- I
DON'T KNOW HOW MANY TIME I HAVE
BUT WE THINK THE APPROACH CAN BE
EXTENDED TO AT LEAST BE A
COMPLIMENT TO GENOME STUDIES OF
POLYMORPHISMS.
AND EXPRESSION POLYMORPHISMS ON
CHROMOSOME 21 MAY BE
PARTICULARLY IMPORTANT.
WE CAN SILENCE THE CHROMOSOMES
WHICH ARE GENETICALLY DISTINCT
AND WE HAVE A PANEL OF CELLS
THAT SILENCE DIFFERENCE ONES.
BY LOOKING AT DIFFERENT DATA
FROM SILENCING DIFFERENT
CHROMOSOME 21s, WE DISCOVERED A
GENE THAT STRONGLY IS GOVERN A
POLYMORPHISM BY ONE OF THE
CHROMOSOME AND THAT IS STRONG
AND I WON'T TALK ABOUT IT TODAY
BECAUSE ERIC STILL WORKING ON
THAT BUT WE'RE LOOKING TO SEE
WHETHER THIS APPROACH COULD BE
APPLIED TO OTHER POLYMORPHISMS
THAT MAY HAVE A MILDER EFFECT.
AND WE THINK IF IT'S JUST
EXPANDING BECAUSE WE JUST DID
THIS IN OUR EXISTING DATA, IF
YOU EXPAND THIS TO A LITTLE BIT
MORE POWERFUL, YOU CAN TELL THIS
OFF GENES AND THIS AFFECTS IT
DIFFERENTLY THAN THESE.
THAT'S JUST AN EXAMPLE.
I WANT TO END -- I'M NOT SURE
MUCH TIME I HAVE BUT WE'RE
WORKING TO TRANSFER ALL THIS
INTO A MOUSE IN VIVO MODEL AND
WE'RE WORKING IN TWO WAYS.
ONE IS WITH THE EXIST MINI GENES
AND ONE IS WITH THE FULL-LENGTH
EXIST.
AND WE MADE A WHOLE TS65DN MOUSE
AND IT'S IN JACKSON LABS.
IT'S GOT A TECHNICAL ISSUE I'LL
TELL YOU ABOUT IF YOU WANT TO
ASK BUT THAT MOUSE IS FREELY
AVAILABLE.
THE GOAL WAS TO TEST FULL LENGTH
EXIST AND WE HAVE CREATED A MINI
GENE MOUSE AND THAT RNA IS
EXPRESSED AND REPRESSING PART OF
THE CHROMOSOME SO WE'RE
CURRENTLY STUDYING THAT MOUSE.
MICE WILL BORN IN UNEXPECTED
RATIO AND BRED THEM OVER A YEAR.
WE ALSO GENERATED CHIMERIC MICE
AND BREEDING THOSE FOR
FULL-LENGTH EXIST.
SO I'M GOING STOP THERE AND CAN
TELL YOU MORE DURING THE
DISCUSSION.
THANK YOU VERY MUCH.
>> THANK YOU, DR. LAURENCE.
OUR THIRD SPEAKER IS COMING UP
THE STAIRS.
I'M GOING INTRODUCE DR. I'LL LET
YOU SAY YOUR OWN NAME.
I'M SORRY.
>> WE'RE NOT GOING MAKE THIS AT
THE END.
THANK YOU FOR YOUR TIME.
I WANT TO THANK YOU THE INCLUDE
TEAM AND THE OPPORTUNITY TO BE
HERE AND PRESENT OUR WORK.
WHAT I WANT TO PRESENT IS ON THE
PRECLINICAL MODELLING OF DOWN
SYNDROME AND HAS SOME DIFFERENT
ANGLE TO SOME OF THE EARLIER
PRESENTATIONS.
WHAT WE ARE INTERESTED IN PART
OF OUR EFFORTS IS UNDERSTANDING
WITH PEOPLE WITH DOWN SYNDROME
HAVE A HIGH RATE OF RECURRENT
INFECTIONS AND PNEUMONIAS AND
GOING TO THE CARDIO VASCULAR
PROBLEMS.
DR. YEAGER PRESENT THE THIS
EARLIER SO I WON'T GO DOWN THAT
BUT SPECIFICALLY WHAT IS THE
IMPACT OF DOWN SYNDROME ON
BIOLOGY AND FUNCTIONING OF THE
LUNG AIRWAY.
THIS IS PRODUCTION AND CAPTURE
INHALED PARTICLES TO TAKE IT OUT
THEIR BODY AND WHAT ABOUT THE
IMMUNE REGULATION AT THE SITE OF
THE LUNG AND THE PULMONARY
TISSUE AND THE IMPACT OF DOWN
SYNDROME ON THE CROSS TALK OF
ORGANS AND THE CROSS TALK
BETWEEN LIKE BONE MARROW AND THE
LUNGS.
THE TUMORAL SYSTEMS ARE DP6 AND
ORGAN AND CHIP TECHNOLOGY.
SO WE STARTED USING THIS WORK I
GOT PULLED INTO DOWN SYNDROME
WORK BY DR. ESPINOZA AND STUDY
THE PATHOLOGIES THAT HAPPENS IN
DOWN SYNDROME.
AND THE FIRST THING WAS THAT WE
STARTED ISOLATING CELLS FROM THE
LUNGS OF DP16 MICE BECAUSE THEY
CARRY A LARGE PORTION OF THIS
CORRESPONDING TO 21 AND
DIFFERENTIATE THEM AND BECOME
CD8 EPITHELIA AND IT TAKES WEEKS
BUT YOU CAN KEEP THEM LONGER IN
VITRO.
INITIALLY WE WANTED TO COMPARE
THE PROCESS WITH GENERATION
CAPABILITY IN TERMS OF
FUNCTIONALITY WHEN THE TISSUE'S
MATURE.
IN TERMS OF THE BARRIER FUNCTION
THEY ARE RELATIVELY SIMILAR
BETWEEN THE DOWN SYNDROME AND
MODEL AND WILD TYPE.
WHEN WE HOOK AT THE FREQUENCY OF
CILIAATED CELLS AND THE CELLS
HAVE LESS NUMBER OF THE CELLS
THROUGHOUT THE CULTURE.
WE VALIDATED THIS BY
IMMUNOFLUORESCENT STAINING AND
IT WAS WHAT WE WERE SEEING.
WHAT ABOUT THE ABILITY AND
PATTERN OF CILIA AND WE COULD
SEE IN THE ONE TYPE HAVE YOU A
DISTRIBUTION AND THIS RANGE HERE
BUT IN THE DP16 MODEL IT'S
SKEWED TOWARDS THE LEFT AND WHEN
YOU LOOK AT THE NUMBERS OF THE
CILIATED BEATING IS TWO LESS
THAN WHAT IS YOU HAVE COMPARED
TO THE WILD TYPE AND THE
CILIATED GOES UP TO 27 TIMES A
SECOND AND ONE DP16 IT'S 25.
AND WE LET THE CELLS PROPEL THAT
TO SEE WHAT HAPPENS.
AND IF YOU LOOK AT THE NUMBERS
THEY'RE RELATIVELY SIMILAR BUT
IN TERMS OF THE ABILITY AND WHAT
IS THE RATE IN MICROMETERS PER
SECOND YOU CAN SEE IT'S
STATISTICALLY LESS ABILITY
BETWEEN THE WILD TYPE AND THE
DP16.
IN OTHER WORDS, THE DP16 HAVE
LESS CILIATED CELLS AND LESS
ABILITY TO BEAT AND THE BEATING
RATE IS ACTUALLY COMPARED TO AN
INHALED PATHOGEN IS LESS IT THAN
THE WILD TYPE.
WHAT'S IT LOOK LIKE IN IMMUNITY?
WE COMPARED THE DNA SEQ AND THE
TRANSCRIPTOME OF THE WILD TYPE
VERSUS THE DP 16 AND LOOKED AT
THE CELLS ARE DIFFERENT AND WHEN
WE LOOK AT THE ENRICHED SETS WE
FOUND THE GENES RELATED TO
IMMUNE RESPONSE ARE ACTIVATED.
NOW, WE SAW THAT AND WERE NOT
SURPRISED BECAUSE WE EXPECTED TO
SEE AN IMMUNE OVERACTIVITY IN
THE CELLS SIMILAR TO THE IMMUNE
CELLS.
WHEN WE STUDIED AFFECTING THEM
WITH THE INFLUENZA VIRUS AND
USED THE PR8 INFLUENZA VIRUS
MODEL WE LOOKED AT A DIFFERENT
SET AND MULTIPLES OF COLORS IS
BIOLOGICAL REPLICATES AND WE ADD
THE VARIOUS AND AFTER TWO HOURS
WE REMOVED THE INNOCULIN AND
THERE'S NO WAY TO TAKE THE VIRUS
OUT.
YOU DON'T HAVE THE FLOW TO WASH
OUT THE VIRUS AFTER THE SYSTEM.
AND WE LOOKED AT THE IMMUNE GENE
EXPRESSION AND I DON'T KNOW HOW
CLEAR IT IS, THE GENES INVOLVED
IN THE IMMUNE ACTIVATION WERE
INDUCED ONE THE INFLUENZA
INFECTION IN WILD TYPE AND DP16
AND WHAT IS DIFFERENT IS THE
MAGNITUDE OF RESPONSE INDUCTION
OF THE GENE EXPRESSION AND WHEN
WE LOOKED AT THE PROTEIN LEVEL
THIS CORRESPONDS BECAUSE FOR
SOME PROTEINS WE COULD SEE THE
CHANGE IS HIGH AND IT'S THE
MAGNITUDE COMPARED TO THE
NON-INFECTED THAT MAKES A
DIFFERENCE.
SOMETIMES YOU HAVE THE CCLs,
2,3, 4 AND 7 WHICH DON'T GET
INDUCED TREMENDOUSLY OR AT ALL
AND WHEREAS THEY HAVE A SEVERE
INDUCTION AND THEY'RE
HYPERINFLAMMATORY WHEN THEY GET
INFECTED.
WE TRIED TO COMPARE THIS IN
VIVO.
THIS IS A COLLABORATION WITH NEW
YORK MOUNT SINAI AND THEY INFECT
THE MOUSE THROUGH THE NOSE AND
DELIVERED THE VIRUS A SUB LETHAL
OF INFLUENZA INFECTION AND THE
NUMBER OF INFLAMMATORY CELLS
MONOCYTES AND NEUTROPHILS HAVE
MORE IMMUNE CELLS IN THE LUNGS
AND IF YOU LOOK AT THE PROTEIN
LEVELS WHAT IS SECRETED INSIDE
THE BRONCHIAL FLUID AS THE
HIGHER LEVELS COMPARED TO THE
WILD TYPE.
THIS IS INTERESTING AND CAN
PARTLY EXPLAIN THE HYP
HYPERINFLAMMATORY TISSUES AND
ONE WAY TO GO IT MICE IS TO USE
ISOLATED CELLS OF PEOPLE WITH
DOWN SYNDROME AND SOMETIMES WE
CANNOT GET ENOUGH SOURCES OF
CELLS.
SO WE BROUGHT IN TECHNOLOGY OF
ORGAN AND CHIP TECHNOLOGY AND
THIS IS A TECHNOLOGY THEY'RE
MORE MACRO FLUIDIC CELL DEVICES
AND CAN MODEL MORE COMPLEX
MODELLING OF HUMAN FUNCTIONING
IN VITRO.
SO OUR LAB HAS DEVELOPED THREE
MAJOR ORGAN AND CHIP SYSTEM
WHICH IS REPRODUCIBLE AND
RELEVANT TO THE STUDY THE FIRST
IS WHAT WE CALL LUNG SMALL I'D
ANDTHE IDEA IS TO HAVE THEM FROM
HUMAN CELLS AND INTERROGATE THE
BIOLOGY AND FUNCTION.
THE SECOND IS A MODEL FOR
LOOKING AT MACRO VASCULATURE
THAT ARE IN THE LUMEN AND TRAP
THE MATRIX AND STROMAL CELLS AND
STUDY WITH THE STROMAL AND
ENDOTHELIAL CELLS AND CONTROL
THE STIFFNESS AND MATRIX AND THE
THIRD IS TO STUDY HEMATOPOIESIS
AND SMALL AREAS IN HUMANS ARE
DEFINED BY A DIAMETER OF 2
MILLIMETER OR SO AND IT'S A SITE
OF EXACERBATION FOR PULMONARY
DISEASE AND GENESIS OF A RANGE
OF PULMONARY COMPLICATION.
WE HAVE A MODEL THAT LOOKS LIKE
THIS.
IT HAS AN AIR XANL AND HAS A
BLOOD XANL.
THE AIR CHANNEL HAS A HEIGHT OF
1 MILLIMETER THAT'S RADIUS OF A
SMALL MEMBRANE.
ON THE TOP WE ADD THE MUCUS
CELLS AND ON THE BOTTOM WE HAVE
THE ENDOTHELIAL CELLS AND THEY
CAN FORM A PACK AND THE DEPTH OF
THE BLOOD CHANNEL IS 100, TO 200
MICRON AND YOU CAN MIMIC THE
POST-
POST-CAPU LATED CELLS AND THESE
ARE THE CILIATED CELLS AND THEY
FORM OTHER SUB TYPES SUCH AS
MUCUS PRODUCING CELLS AND WE
HAVE BASAL CELLS AND THE BARRIER
FUNCTION AND THIS IS WHAT YOU
SEE THE ENDOTHELIAL CELLS AND
HAVE CD31 AS WELL AS THE
MACHINERY AND IMPORTANT FOR
CAPTURE OF CIRCULATING IMMUNE
CELLS.
THE OTHER MODEL IS THE EXTRA
CELLULAR MATRIX CHIP THAT ALLOWS
US TO HAVE THE MODEL AND I DON'T
WANT TO BORE YOU WITH THE DATA
BUT I WANT TO EMPHASIZE ONE IS A
LOT OF PEOPLE WHEN THEY ARE WANT
TO STUDY THE CELLS THEY CALLED
IT ON THE MICROFLUIDIC SYSTEM OR
CREATE SQUARE SHAPED OR R
RECTANGULAR CHANNELS BUT IT'S
NOT PHYSIOLOGICAL.
WE HAVE A ROUNDED OVAL SHAPE AND
THE IMPORTANCE OF THIS IS IF YOU
DON'T HAVE THE RIGHT SHAPE
CIRCULAR OR OVAL YOU WON'T HAVE
A UNIFORM DISTRIBUTION AND
THAT'S IMPORTANT.
IN THIS CASE FOR EXAMPLE THE
RECTANGULAR HAS SQUARE SHAPE AND
YOU HAVE HUGE ISOLATION OF SHEER
STRESS SENSING IN THE
ENDOTHELIAL LEVEL.
THEY DON'T SEE THE SAME THING
BUT IN THE SECULAR HAVE YOU MORE
OR LESS THE SAME SENSING
THOUGHT.
THE SECOND THING IS THE LENGTH
OF THE CHANNEL IS VERY
IMPORTANT.
IF SOMEONE SAID WHAT IS THE
FORMAT AND I HAVE IT EIGHT MI
MILLIM
MILLIMETER.
THERE'S AN AREA FROM THE
BEGINNING OF THE FLOW COMING TO
THE CHANNEL UNTIL THE FULLY
DEVELOPED HERE IS PRESENT AND
THAT'S CALLED LIKE DEVELOPING
FLOW.
IF YOU DON'T CORRECT FOR THAT
YOU WON'T SEE THE SHEAR STRESS
AND IF YOU WANT TO SEE THE
PATHOLOGY IN THE B CELLS OR T
CELLS IT'S IMPORTANT TO CORRECT
FOR THAT.
THE FIRST THING I WANT TO SAY IN
OUR MODEL WE CAN CONTROL FOR THE
COMPOSITION OF MATRIX AND
STIFFNESS.
WE MIMIC IN THIS CASE BOTH
NORMAL AND STIFFNESS WHICH IS
ABOUT 1 TO 2 STIFFNESS AND IN A
FIBROTIC YOU GROUP TO 30 PILO
AND WHEN YOU PUT THEM IN THE
MATRICES YOU DON'T HAVE THE
NATURAL STIFFNESS YOU HAVE IN
THE BODY.
SO THIS IS HOW THE MODEL LOOKS
LIKE.
YOU CAN SEE THE ENDOTHELIAL
CELLS AROUND THE ROUNDED CHANNEL
AND YOU SEE A MATRIX AND SEE THE
FIBROBLASTS.
THEY WANT TO HAVE IT DISPERSE
THE THROUGHOUT THE MATRIX.
THE LAST MODEL IS A MODEL FOR
HEMATOPOIESIS AND WE BRING IT IN
BEFORE THE CORD BLOOD AND MIX
THEM WITH THE MESENCHYMAL STEM
CELLS AND WE CAN DISPERSE THE
CELLS THREE DIMENSIONALLY AND
LET THEM DO THE JOB AND THEY
FORM THE POPULATION AN BECOME
MYELINATED AND WE CAN STUDY
LEUKOCYTE EGRESS.
THIS IS DATA HOW IT LOOKS LIKE
AS EARLY AS AT SEVEN DAYS AND
THESE ARE ENDOTHELIAL CELLS AND
TO SHOW IT COMPARED TO THE OTHER
CULTURES AND LASTLY IS WHAT
WE'RE ABLE TO DO.
WE INTRODUCED IN THE VASCULATURE
A CHEMOKINE A LIPID MEDIATOR AND
LOOK AT CELLS AFTER HOW YOU
WOULD DO IT OTHERWISE IN AN
IMMUNE CONTEXT AND PUT IN YOUR
MONOCYTES AND NEUTROPHILS AND
SEE WHAT DROPS OUT.
SECOND, YOU GET THE DROPS AND IT
STAYS THERE AND IN THE BODY
CELLS ARE PRODUCED AND LIVE.
IN OUR SYSTEM THEY COME AND GO.
SO WHAT WE DISCOVERED IS THAT
THERE'S NO LINEAR RELATION
BETWEEN THE TYPE OF THE HEMOTAX
ISIS STARTS AND THE CELLS NEED
TO BE REPLENISHED.
NOW, I MENTIONED THIS -- I KNOW
I'M OUT OF TIME BUT ONE SLIDE I
WANT TO SHOW IS YOU DEVELOP THIS
WITHIN A PRIMARY CELLS AND HOW
TO APPLY THEM WITH THE IPSC
CELLS.
THAT'S WHERE WE ARE.
THIS IS COLLABORATION WITH KELLY
SULLIVAN.
WE OBTAIN THE CELLS FROM WILD
TYPE AND TRISOMIC SUBJECTS AND
WE'RE ABLE TO PUT THEM HERE.
YOU CAN SEE THE CROSS SECTION AS
WE GO THROUGH THE CHANNEL AND
IT
IT'S CILIA AND THEY'RE
MUCOCILIATED CELLS.
THIS IS SOME OF WHAT I JUST
MENTIONED AND HOPE IT OPENS UP
THE PATH FOR ENABLING IT AS A
CHIP ING AND WITH THE
MODERNIZATION ACT 2.0 THERE'S
MORE INTEREST IN THE TECHNOLOGY
TO ACCELERATE DRUG DEVELOPMENT
AND TAKING THERAPEUTICS INTO
CLINIC AND EVEN CLINICAL TRIAL
IN CHIP.
WITH THAT I'D LIKE TO THANK YOU
FOR LISTENING AND THESE ARE OUR
COLLABORATORS AND FUNDING
AGENCY.
THANK YOU.
>> THANK YOU.
I'D LIKE TO ASK ALL THE SPEAKER
TO TAKE A SEAT AT THE TABLE AND
WHILE THEY DO THAT, IF ANYBODY
HAS QUESTIONS THERE'S MICS IN
THE AISLE AND I DO ASK ANYBODY
WHO ASKS A QUESTION, PLEASE
IDENTIFY YOURSELF AND ASK YOUR
QUESTION.
>> I'M FROM NATIONWIDE
CHILDREN'S HOSPITAL THANK YOU
FOR THE TALK.
A QUESTION FOR DR. LAWRENCE.
YOU ASKED AXIS TO SILENCE THE
ADDITIONAL CHROMOSOME 21.
AND FEMALES ALREADY ACCESS THE
MECHANISM OVER THERE.
I GUESS YOUR PAPER YOU USED THE
MER LINE.
DO YOU HAVE THOUGHTS ON
SILENCING CHROMOSOME 21 IN
FEMALE.
>> WE'RE CURRENTLY DOING THAT
RIGHT NOW BUT IT WOULD WORK FINE
BECAUSE IN NATURAL PEOPLE THERE
ARE PEOPLE WITH THREE X
CHROMOSOMES AND MANY DON'T KNOW
THEY HAVE THREE X CHROMOSOMES.
THE SYSTEM WOULD NOT BE
EXCLUSIVE TO MALES.
WE DID THAT INITIALLY BECAUSE
IT'S EASIER FOR US TO LOOK AT
THE RNA AND WHERE IT IS AND NOT
HAVE TO WORRY ABOUT LOOKING AT
THE NATURAL X BUT THE SYSTEM
WORKS EITHER WAY.
>> THERE'S ALSO A PAPER USING
CRISPR CAS 9 TO REGENETICALLY --
GENETICALLY REMOVE THAT.
DO YOU HAVE THOUGHTS ON THAT?
>> I COULD BE AN ALTERNATIVE
APPROACH BUT I WOULD BE AFRAID
THE PIECES YOU CUT COULD STICK
TO OTHER CHROMOSOMES BECAUSE
WHEN YOU HAVE A TELOMERE BUT I'M
NOT SURE EXACTLY WHAT'S BEEN
DONE.
>> THANK YOU.
>> A QUESTION OVER HERE.
>> YOU WERE MENTIONING GENETIC
BACKGROUND AS BEING A POSSIBLE
VARIABLE HERE.
I'M WONDERING IF YOU HAVE MOVED
YOUR XIST SYSTEM AND IF THE
PATHWAYS ARE DEPENDENT ON WHAT
YOU'RE SILENCING IN?
>> WHAT I SHOWED WAS WE'RE
SILENCING DIFFERENT CHROMOSOME
21s IN THE SAME GENETIC
BACKGROUND WHICH I THINK IS A
POWERFUL APPROACH.
>> I AGREE.
>> WE STARTED DOING THAT.
WE RECENTLY PUT OUR SYSTEM --
WE'RE JUST NOW DOING THE CLONES
FOR ANOTHER INDIVIDUAL WHO IS A
FEMALE, BY THE WAY.
SO PRETTY MUCH EVERYTHING WE'VE
DONE WAS IN THE BACKGROUND WHICH
I UNDERSTAND IS A CONSIDERATION.
BUT WE'RE JUST TRYING TO SEE
WHAT HAPPENS WHEN YOU MANIPULATE
21 AND GET RID OF ALL THE
VESSELS.
>> YOU CAN'T DO IT ALL.
>> I WENT PAST MY
ACKNOWLEDGEMENT SLIDE.
I WANT TO THANK ERIC LARSON AND
MY COLLABORATOR IN THE MOUSE AND
I WANT TO THANK NIGMS.
SORRY, NICHD.
>> I'M FROM TEXAS UNIVERSITY.
I HAVE A QUESTION ABOUT THE
TRISOMIC RATS.
I THINK IT'S A NICE EXTENSION OF
OUR INFORMATION AND CURIOUS IF
YOU IDENTIFIED ANY CRANIOFACIAL
ABNORMALITIES OR TOOTH ERUPTION
ISSUES OR ANY OTHER PHENOTYPIC
DIFFERENCES?
>> THANKS NOR QUESTION.
-- FOR THE QUESTION.
IN TERMS OF ONE OF THE RATS
WE'VE MADE, ONE IS AN ARNO 20
AND THE OTHER IS 11.
THERE'S NO CRANIAL DIFFERENCES
AT 50 BONY LANDMARKS, HOWEVER,
IN THE ARNO 20 RATS THEY'RE
READILY APPARENT COGNITIVE
DIFFERENCES AND DO ALL THE MAZES
DIFFERENCE.
WHILE THERE'S NO STRUCTURAL
DIFFERENCE IN CRANIAL OR TEETH
ARE DIFFERENT.
>> HAVE YOU DONE MRI OR DONE AN
CT OF THE SPINE OR LONG BONES?
>> HAVE NOT.
THANK YOU FOR THE QUESTION.
>> LARRY BASER, NATIONAL HEART,
LUNG AND BLOOD INSTITUTE.
IN PEOPLE WITH COVID IS THERE AN
AREA OF ACTIVE INVESTIGATION?
YOU SHOWED AND WE KNOW THE ACUTE
EFFECTS ARE MORE PROFOUND AND
MORE FATAL IN PEOPLE WITH DOWN
SYNDROME.
I'M WONDERING ABOUT THE
LONG-TERM EFFECT OF PEOPLE WITH
THAT.
DO YOU KNOW?
>> DON'T KNOW.
GREAT QUESTION.
THERE'S IN THE LITERATURE SOME
DOUBT IN SOME PEOPLE'S MIND
THERE'S A LONG COVID.
>> I THINK WE KNOW THERE IS.
>> WE CAN TALK AFTER.
THERE'S PLENTY OF DEBATE THAT
SUGGESTS THE SEQUELAE ARE
RELATED TO COVID BUT I'M NOT
FAMILIAR WITH ANY SPECIFIC DATA
ABOUT LONG-TERM EFFECTS.
>> DOWN SYNDROME PEOPLE HAVE
INCREASED SUSCEPTIBILITY TO
CARDIO AND PULMONARY EFFECT.
>> AS FAR AS I KNOW, NO.
>> THANKS.
>> BEFORE I DO MY QUESTION,
JOAQUIN HE ESPINOZA COLORADO.
AND THERE WAS A REPORT OF A
DOCTOR WHO CARES FOR ADULTS WITH
DOWN SYNDROME AND LONG-TERM
SEQUELAE AND RELATED QUESTION,
SO FIRST OF ALL, YOU'RE RIGHT,
WE SHOULD HAVE LUNG INFECTIONS
OF THE TOP OF EVERY SLIDE AND
ALZHEIMER'S AND OTHERS THINGS
ARE RIGHT.
PEOPLE WITH DOWN SYNDROME ARE
DYING AT A DISPROPORTIONATE RATE
OF PEOPLE WITH DOWN SYNDROME AND
THE IMMUNE RESPONSE IS GOING
BANANAS.
THE GRAPHS YOU WERE SHOWING
THREE AND THREE FOUR TIMES
KRAOF
GREATER CYTOKINES.
IS THAT HOW WE PROTECT ADULTS BY
TONING DOWN THE CYTOKINE STORM
ARE YOU SEEING THAT AS A
THERAPEUTIC OPPORTUNITY?
>> IT CAN BE A PATH TO
DEVELOPING THERAPEUTIC.
ONE AREA WE HAVE NOT EXPLORED OF
SECRETION OF INNATE
ANTIMICROBIAL DIVERSE OF MUCOSA.
ANY SORT OF PROTEINS THAT ARE
SECRETED CAN ADHERE TO THE VIRUS
BEFORE THEY EVEN SIMULATE THE
CELLS TO CAUSE IMMUNE
ACTIVATION.
HAVE THEY CHANGED OR NOT?
THAT COULD POTENTIALLY BE ONE
PATH.
IF I PUT MY BET BASED ON THE
CURRENT DATA I WOULD SAY THEY'RE
TARGETING THE IMMUNE PATH IS
LIKELY FRUITFUL IN AMELIORATING
THE SYMPTOMS.
>> THANK YOU.
>> WE HAVE ONE FOR ONE MORE
BRIEF QUESTION.
>> ARE YOU GUYS GOING TO WORK
TOGETHER TO DO PRIMARY,
SECONDARY INFECTION MODELS?
>> I DON'T KNOW IF WE'LL WORK
TOGETHER ON THAT BUT WE'RE
WORKING SEPARATELY TO DO THAT.
>> GREAT, I'LL ASK YOU LONG
QUESTIONS LATER.
>> I JUST WANT TO MENTION THAT
WE STARTED TO DO A TEST WHETHER
VIRAL SUSCEPTIBLE WAS DONE WITH
SILENCING THE CHROMOSOME 21 AND
WERE WORKING WITH ROBERT
FINCHBERG WHO UNFORTUNATELY DIED
DURING THE WORK BUT THE
PRELIMINARILY RESEARCH SHOWED
THE VIRUS DID REPLICATE MORE
WITHOUT SILENCING SO THERE MAY
BE DIRECT EFFECT.
>> JOIN ME IN THANKING THE
SPEAKERS.
WE'LL NOW TAKE A SHORT BREAK AND
WE'LL START AGAIN AT 10:45.
FOR THOSE MEMBERS OF THE PANEL
WHO WILL BE JOINING ME ON THE
STAGE AT 10:45, IF YOU CAN COME
TO THE FRONT AS EARLY AS AS
POSSIBLE.
MANY THANKS.
>> WE'RE READY TO START OUR
FIRST PANEL OF THE MEETING
FOCUSSED ON BASIC AND
TRANSLATIONAL RESEARCH SCIENCE.
SO THE STRUCTURE OF THESE PANELS
IS AS YOU SEE WE HAVE A NUMBER
OF OUR COLLEAGUES JOINED ME AT
THE TABLE.
EACH WILL GIVE A SHORT
PRESENTATION AND THEN WE'LL HAVE
THE REMAINDER OF OUR HOUR TO
TAKE QUESTION.
WE WOULD LIKE TO SEE THIS BE
MORE OF A DISCUSSION PLATFORM.
A DISCUSSION SESSION.
WITH A FOCUS ON IDENTIFYING THE
CHALLENGES OF USING MODEL
SYSTEMS FOR BASIC RESEARCH AND
POSSIBLE SOLUTION.
OUR FIRST SPEAKER IS RANDAL
ROPER.
>> WHEN WE TALK ABOUT MOUSE
MODEL OR ANY MODEL WE WANT TO
UNDERSTAND HOW DOES THE MODEL
RECAPITULATE THE CONSTRUCT OR
THE GENETICS WE MIGHT SAY?
THE NEXT IS THE FACE OR HOW WELL
THE MODEL MIMICS THE MEC LAR OR
PHENOTYPES WE SEE IN THE MODEL
AND THE THIRD THING WE WANT ASK
ABOUT IS WHAT IS THE PREDICTIVE
VALUE OF THE MODEL AND HOW WILL
THE MODEL HELP US PREDICT WHAT
WE MIGHT FIND IN HUMANS?
SO THERE'S A NUMBER OF DIFFERENT
MOUSE MODELS OF DIFFERENT
SYNDROME AND WE HAVE MOUSE
MODELS WITH A SEGMENTAL TRISOMIC
AND TRANS CHROMOSOMIC AND GENE
MODELS AND I LISTED THEM DOWN
BELOW.
THIS IS A SCHEMATIC OF HUMAN
CHROMOSOME 21.
WE HAVE TWO TRANS CHROMOSOMIC
MOLDS AND MANY ARE REPRESENTED
ON THREE MICE CHROMOSOMES AND A
NUMBER WHICH ARE DUPLICATION
MODELS.
WE'RE FORTUNATE IN DOWN SYNDROME
TO HAVE A PLETHORA OF SO MANY
MODE
MODELS E SPECIALLY MOUSE MODELS
WITH ZEBRAFISH OR CELL LINES.
IF YOU'RE ABLE TO ATTEND THE
T21RS MEETING WE HAVE A SESSION
DEVOTED TO THE OTHER MOUSE
MOLDS.
I OFTEN GET THE QUESTION, WHICH
MOUSE MODEL IS THE BEST ONE?
I HAVE THE ANSWER.
IT DEPENDS.
WHAT DOES IT DEPEND ON?
WELL, WE'RE GOING TALK ABOUT A
NUMBER THESE THINGS.
YOU KNOW, YOU WANT TO LOOK AT
WHAT OTHERS HAVE DONE AND WHAT
OTHERS ARE USED AND YOU WANT TO
SEE WHAT THE LITERATURE SAYS
ABOUT THE DIFFERENT MOUSE
MODELS.
IF THERE'S NEW ONES AND WHAT ARE
THE IMPROVEMENTS AND IF YOU LOOK
AT THE PHENOTYPE IF THERE'S NO
INFORMATION I WOULD ENCOURAGE
THAT YOU USE AT LEAST TWO
DIFFERENT DOWN SYNDROME MOUSE
MODELS.
SO YOU NEED TO KNOW YOUR MOUSE
AND NEED TO KNOW THINGS LIKE THE
GENETIC CONTENT, WHAT ARE GENES
ARE COPIED AND WHAT OTHER
INFORMATION INHERITED AND SOME
ARE NOT HOMOLOGOUS TO CHROMOSOME
21.
DOES IT HAVE PHENOTYPES YOU
EXPECT AND WHAT ARE THE
DIFFERENCES?
PART OF MY LAB STUDY PHENOTYPES
ASSOCIATED WITH DOWN SYNDROME.
SEE A FEMUR MUCH A MOUSE AND AT
THE DISTAL END THE TRABECULAR
BONE AND THE TRIPLICATED MOUSE
AND HAVE YOU THE GRAY LINES ARE
GREATER THAN UPLOID AND YOU SEE
THAT IN CORTIC CAL BONE MALES
AND FEMALES HAVE THE SAME
CORTICAL BONE.
WE GET SEX DIFFERENCE AND
THERE'S THE TS69 AND DP16 THIS
THE TRABECULAR BONE.
WE SEE MALES HAVE REDUCED
TRABECULAR BONES AND TRISOMIC
MICE DO AND FEMALES DON'T BUT IN
THE CORTICAL BONE WE SEE A
DIFFERENCE WE SEE A REDUCTION ON
THE STRAINS.
THE LAST POINT I'D LIKE TO MAKE
IS A LITTLE BIT ABOUT SEX
DIFFERENCES.
WE JUST PUBLISHED THE DATA.
WHAT WE SEE HERE IS WE'RE
LOOKING AT DIRK 1A EXPRESSION.
THIS IS PROTEIN EXPRESSION AND
WE'RE LOOKING AT POST NATAL DAY
SIX AND THE DIRK 1A EXPRESSION
IS UPREGULATED IN THE
HIPPOCAMPUS AND CEREBRAL CORTEX
AND CEREBELLUM AND IN P15 IT'S
UPREGULATED IN MALES BUT NOT
FEMALES AND FROM CONCEPTION WE
SEE IT'S LOWERED AT P6 MALES AND
FEMALES BUT IN OUR FEMALES WHERE
DIDN'T SEE UP REGULATION WE CAN
KNOCK DOWN ONE COPY OF DYRK1A
EXPRESSION.
VERY IMPORTANT TO LOOK AT WHAT'S
GOING ON IN MALES AND FEMALES.
IN WORKING WITH MOUSE MODELS WE
HAVE TO UNDERSTAND THE
DIFFERENCES BETWEEN MOUSE
MODELS.
WE WANT TO USE THE BEST MODEL
FOR GENETIC AND PHENOTYPIC
HYPOTHESIS THAT HOPEFULLY
PREDICT WHAT'S GOING ON IN
HUMANS.
IT'S BEST TO USE TWO OR MORE
MOUSE MODELS IN EVALUATING
DIFFERENCES BETWEEN THE SEXES.
THIS WORK WAS DONE WITH THE LAB,
LONG TIME COLLABORATOR CHARLIE
GOLET AND I HOPE YOU'LL VISIT
THEIR POSTERS TO TALK WITH THEIR
WORK.
THANK YOU AND I THINK WE'LL GO
TO THE NEXT PRESENTATION FROM
THERE.
>> OUR NEXT PRESENTER IS TIFFANY
GLASS.
>> THANKS FOR THE OPPORTUNITY TO
SHARE THOUGHTS TODAY.
I'M FROM THE UNIVERSITY OF
WISCONSIN-MADISON IN THE
DEPARTMENT OF SURGERY,
DEPARTMENT OF LARYNGOLOGY.
I'LL GIVE A QUICK INTRODUCTION
TO THE PREMISES BEHIND SOME OF
THE AND SHOW A FEW EXAMPLES MUCH
THE TYPES OF DATA SETS WE USE
USING THE EXPERIMENTAL PARADIGMS
AND SHARE THOUGHTS ON AREAS TO
TRANSLATING BASIC RESEARCH TO
BENEFIT PEOPLE WITH DOWN
SYNDROME.
FOR SOME INDIVIDUALS, DOWN
SYNDROME CAN ENTAIL DIFFICULTIES
IN FEEDING AND SWALLOWING AND
CAN MANIFEST IN DIFFERENT WAYS
DELVE DEPENDING ON THE
DEVELOPMENT STAGE.
DYSPHASIA WILL LOOK DIFFERENT
FROM EATING AND DRINKING IN
SWALLOWING AT OTHER OLDER
RELATED TO COMORBIDITIES RELATED
TO AGING.
WE KNOW THE CHALLENGING WITH
EATING, DRINK AND SWALLOWING CAN
INVOLVE A WIDE VARIETY OF
COMORBIDITY.
CONSIDERING DIFFERENCE IN
DEVELOPMENT OR LIFE STAGE AND
THE VARIETY OF CO-MORBIDITY.
THESEERS CAN CAN LOOK VERY
DIFFERENT BETWEEN DIFFERENT
INDIVIDUALS WITH DOWN SYNDROME.
TO THE SWALLOWING IS IMPORTANT
AND WE STUDY THE TONGUE MUSCLE
SYSTEM AND WE LOOK AT LARGE HIGH
RESOLUTION MICROSCOPY OF TONGUE
TISSUE SECTION FROM THE DN MOUSE
MODEL OF DOWN SYNDROME AND CAN
STAIN THE SECTION FOR DIFFERENT
MARKERS OF TONGUE MUSCLE BIOLOGY
AND THIS LETS US ANALYZE EIGHT
OF DIFFERENCES IN TONGUE MUSCLE
MYOFIBERS AND CAN STUDY
MICROANATOMICAL STRUCTURE AND WE
USE A PARADIGM TO STUDY TONGUE,
MUSCLE PHYSIOLOGY AND WE FOUND
IT DEMONSTRATES EARLY ONSET OF
TONGUE MUSCLE FATIGUE AND U
EUPLOID CONTROLS AND WE QUANTIFY
AND EVALUATE SWALLOWING
FUNCTIONS OF MOUSE MODELS AND
VIDEO FLUOROSCOPY IS CONSIDERED
ONE GOLD STANDARD METHOD TO
EVALUATE SWALLOWING FUNCTIONING
IN HUMANS AND HAVE BEEN ABLE TO
ADAPT THEM TO QUANTIFY ASPECTS
OF SWALLOWING FUNCTION IN THE
MOUSE MODEL.
AS WE CONTINUE TO WORK ON THE
STUDIES WE STARTED TO
DEMONSTRATE WAYS TO SHARE THE
DATA SETS WITH THE RESEARCH
COMMUNITY.
SO I'M SO GRATEFUL TO HEAR THE
INCLUDE PROJECT STARTING TO HELP
US DEVELOP THE INFRASTRUCTURE TO
SHARE THE TYPES OF DATA SETS.
NEXT I'LL COMMENT ON CHALLENGES
FOR TRANSLATABILITY OF BASIC
DOWN SYNDROME RESEARCH.
MY SON MAX HAS DOWN SYNDROME.
HE'S 13 YEARS OLD.
HE'S NON SPEAKING BUT
COMMUNICATING USING ELECTRONIC
AUGMENTATIVE COMMUNICATION OR
AAC.
I SHOWED SOME SLIDES TO MAX AND
ASKED HIM IF IT'S OKAY IF WE
SHARE SOME INFORMATION ABOUT HIM
TO HELP SCIENTISTS AND HE USED
CHAT POWER TO SAY YES, THIS IS
OKAY WITH HIM.
SO MAX IS AUTISTIC AND HAS DOWN
SYNDROME AND AUTISM AND INFANT
AS TODDLER HAD DELAYS IN WEANING
OR TRANSITION FROM DRINKING FROM
A BOTTLE TO BE ABLE TO DRINK OUT
OF AN OPEN CUP.
IT TOOK HIM A LONG TIME TO BEGIN
TO TRANSITION TO TOLERATE A
RANGE FOODS AND NOT MANY FOODS
HE'S ABLE TO EAT AND CAN CHEW
BUT MAY SPIT WITHOUT SWALLOWING.
HE'S NOT ABLE TO EXPLAIN TO US
WHAT HIS EXPERIENCE IS LIKE WHY
IS HE SPITTING IT OUT RATHER
THAN SWALLOWING IT.
HE HAS COMMUNICATION
DISABILITIES AND SEVERAL OTHER
SUPPORT NEEDS.
SO OUR EXPERIENCE HAS BEEN THAT
SOME ASPECTS OF VIDEO FLEUR OWE
SCOPIC STUDY STUDIES AND ROUTINE
EXAMS AND DENTAL CLEANINGS ARE
NOT STRAIGHTFORWARD FOR HIM AND
WHAT IS A REGULAR OFFICE VISIT
MAY REQUIRE SEDATION IN THE O.R.
FOR MAX.
HE'S PERCEIVED BY OTHERS AS
UNABLE TO FOLLOW ONE-STEP
INSTRUCTIONS OR COMMUNICATE AND
UNABLE TO REPORT SIDE EFFECTS
AND ADD TO EXPERIENCES THAT ARE
ASSOCIATED WITH MEDICAL
PROCEDURES.
WE FOUND OVER THE PAST 10 YEARS
THAT DAYCARES IN SCHOOLS IN OUR
COMMUNITY WERE CONSISTENTLY
UNABLE TO PROVIDE SOME OF THE
APPROPRIATE ACCOMMODATIONS WE
NEEDED TO SUPPORT MAX'S
COMMUNICATION DISABILITIES AND
FEEDING CHALLENGES.
THESE TYPES OF BARRIERS TO
DISABILITY ACCOMMODATIONS CAN BE
DEVASTATING FOR HEALTH AND
DEVELOPMENT.
AND THESE ARE DISABILITY
ACCOMMODATIONS FEASIBLE AND MAY
BE REQUIRED IN THEORY BUT IN
SOME COMMUNITIES MAY NOT BE PLUM
-- AVAILABLE DUE TO FUNDING OR
COMPLICATED SOCIAL, STRUCTURAL.
THESE BARRIERS WE MIGHT THINK
ABOUT WITHIN THE FRAMEWORK OF
THE SOCIAL MODEL OF DISABILITY
RATHER THAN THE MEDICAL MODEL OF
DISABILITY.
BECAUSE OF THESE BARRIERS SOME
INDIVIDUALS WITH DOWN SYNDROME
MAY NOT ABLE TO FULLY ACCESS THE
BENEFITS OF TREATMENT OPTION AND
IF THE BARRIERS AREN'T
ADDRESSED, SOME INDIVIDUALS WITH
DOWN SYNDROME MAY NOT BE ABLE TO
ACCESS THE BENEFITS OF THE
FUTURE OR EMERGING KNOWLEDGE OR
TREATMENTS WE'RE ALL WORKING ON
NOW WITH OUR RESEARCH.
AND I THINK THIS MIGHT IMPACT
THE RESEARCH.
WE WANT RESOURCES AND DISCOVERY
WE GENERATE WITH OUR RESEARCH TO
BE ABLE HELP EVERYBODY
REGARDLESS OF THEIR SUPPORT
NEEDS.
WE WANT TO HELP PEOPLE WITH LOW
SUPPORT NEEDS AND ALSO PEOPLE
WITH HIGH SUPPORT NEEDS.
SOME CONCLUDING THOUGHTS, BASIC
RESEARCH IS SO ESSENTIAL BECAUSE
IT HELPS US REFINE IDEAS AND
HYPOTHESES AS MUCH AS POSSIBLE
ABOUT BRINGING THEM TO THE
CLINIC.
AND THIS VERY VALUABLE IF ACCESS
TO CLINICAL CARE MAY BE COMPLEX
FOR SOME PEOPLE WITH DOWN
SYNDROME.
I THINK INFORMATION AND
SUPPOR
SUPPORTING VARIABILITY WILL BE
NEEDED TO TRANSLATE BASIC
RESEARCH TO BENEFIT INDIVIDUALS
WITH DOWN SYNDROME.
AND THESE ARE OUR
ACKNOWLEDGEMENTS.
THANK YOU.
>> THANK YOU.
OUR NEXT PANEL TO SPEAK WILL BE
LAU
LAURA DERUISEAU.
>> THANK YOU TO THE ORGANIZERS
FOR RUNNING A SMOOTH MEETING AND
FOR THE TOWN HAVE THESE
DISCUSSIONS TODAY.
OF IT -- THE OPPORTUNITY TO HAVE
THESE DISCUSSIONS TODAY.
I WANT TO START WITH OVER ALL
CONSIDERATIONS IN VARIABILITY IN
MOUSE STUDIES.
I'LL TALK ABOUT SOME SOURCES.
CAGE STYLE GROUP VERSUS SINGLE
HOUSING, AMBIENT TEMPERATURE OF
HOUSING AND OF COURSE CIRCADIAN
DIFFERENCES DEPENDING ON THE
PHYSIOLOGICAL VARIABLE YOU'RE
INVESTIGATING.
I WANT TO PLANT A SEED THAT MICE
ARE NOT SMALL RATS.
SOME INVESTIGATIONS MAY NEED
SOME TWEAKING BEFORE BEING
IMPLEMENTS IN MICE.
AND BRIEFLY MANY IN SYSTEMS USE
THE SYSTEM ON THE LEFT THE
VENTILATED CAGE SYSTEM AND MAYBE
THE MORE TRADITIONAL MODEL WOULD
BE THE WIRE TOPPED CAGE WHERE
MICE CAN CLIMB.
AND ONE SOURCE OF VARIABILITY
THAT CAN BE AGAIN DIFFERENT
LABORATORIES AND THEY OBSERVED
LOWER BODY WEIGHT AND HIGHER
CORE TEMPERATURE IN THE ANIMALS
THAT HAD ACCESS TO THE WIRE
TOPPED CAGE AND MORE THAN HALF
THEIR MICE HAD TO BE SEPARATED
DUE TO FIGHTING.
SO HALF OF THEIR ANIMALS WERE
SINGLY HOUSED AND GROUP HOUSED.
THAT'S ANOTHER SOURCE OF
POTENTIAL VARIABILITY.
THERE'S MORE PUBLICATIONS ON
GROUP VERSUS SINGLE HOUSING BUT
WE STILL HAVEN'T SOLVED THE
PROBLEM AND IT'S ESPECIALLY
IMPORTANT FOR AGING STUDIES OF
MICE HAVE TO BE SEPARATED FOR
FIGHTING AT SOME POINT.
AND IT'S OFTEN RECOMMENDED TO
GROUP HOUSED MICE BECAUSE
THEY'RE SOCIAL ANIMALS HOWEVER,
MALE GROUPED MICE HAVE HIGHER
CORTISOL LEVEL AND HAVE TO BE
SEPARATED AT A LATER TIME POINT.
THE PAPER WITH GROUP HOUSING IN
FEMALE MOUSE AND ANOTHER
RECOMMENDATION IS THEY CAN
HUDDLE TO MAINTAIN BODY
TEMPERATURE AND HIS GROUP
OBSERVED THAT WASN'T THE CASE.
THAT WAS WITH FEMALE MICE.
HIS GROUP HAS DONE WORK WITH
AMBIENT TEMPERATURE AND
AUTONOMIC FUNCTION.
THIS DATA SHOWS AS TEMPERATURE
GOES DOWN, FROM 30 TO 20 THE
DOTTED LINE AND ON THE OTHER
SIDE FROM 20 TO 30, HEART RATE
IS ADVERSELY RELATED.
SO AS TEMPERATURE GOES FROM 30
TO 20, HEART RATE GOES UP AND
FROM 20 TO 30 HEART RATE GOES
DOWN AN IT'S AUTONOMICLY
MEDIATED SO IT'S IMPORTANT TO
REPORT THE TEMPERATURES.
WE CHOSE THE MID POINT BETWEEN
20 AND 30 AND THESE ALL WERE
PERFORMED WITH THE WIRE TOP
CAGES.
WE HAVE SHOWN BLOOD PRESSURE IS
LOWER IN DS69DN AND DID NOT
CHANGE BETWEEN 6 AND 12 MONTHS
AND IN WILD TYPE THERE'S AN
INCREASE IN BLOOD PRESSURE AS
THEY MATURE DUE TO ARTERIAL
STIFFNESS AN THERE'S A STRAIN
AND AGE EFFECT AND INTERACTIONS.
SO IT'S IMPORTANT WE ARE ABLE TO
STUDY THE ANIMALS AT VARIOUS
TIME POINTS BECAUSE SOME THINGS
WILL NOT MANIFEST UNTIL A
DIFFERENT AGE POINT AND HIGH
POXEMIA IS ANOTHER TIME POINT
AND THEY'RE DEVELOPING THEIR
BREEDING AND HAVE AS MANY HIGH
POXEMIA AND IT'S IMPORTANT WE
CONTINUE TO STUDY THEM AND
OBSERVED THE SAME PHENOMENON IN
MORE ELABORATE STUDY OF B6
ANIMALS.
AND LASTLY, WE DON'T SEE
DIFFERENCES IN GAS EXPOSURES.
WITH HYPERCAPNIA AND SEE THE
RESPIRATORY SYSTEM AN DON'T SEE
DIFFERENCES BETWEEN 12 MONTHS
BETWEEN TS65DN AND WILD TYPE BUT
THERE'S A BLUNTED RESPONSE AT 12
MONTHS.
THE DATA TO THIS POINT WERE
PERFORMED IN THE LIFE CYCLE BUT
IT'S IMPORTANT TO RECOGNIZE
THERE'S DIFFERENCES ACROSS THE
CIRCADIAN CYCLE AND THEY'RE
LOWER IN THE LIFE CYCLE COMPARED
TO THE LIGHT AND LOWER IN TS65DN
COMPARED TO WILD TYPE.
AND WHEN WE COMPARE BREEDING
WE'RE ABLE TO OBSERVE
DIFFERENCES AND WILD TYPE
ANIMALS HAVE AN INCREASE IN THE
RESPONSE TO BOTH HYPOXIA AND IN
THE DARK CYCLE COMPARED TO THE
LIGHT CYCLE AND THE TRISOMIC
ANIMALS THE 65DN HAVE NO
DIFFERENCE BETWEEN LIGHT AND
DARK CYCLE RESPONSES AND WE'RE
ABLE TO RECOGNIZE THESE EARLIER
WHEN COMPARING ACROSS THE LIGHT
AND DARK CIRCLES.
BRIEFLY, CAGE STYLE SINGLE
VERSUS GROUP HOUSING AND AMBIENT
TEMPERATURE AND TIME OF DAY ARE
ALL POINTS OF DISCUSSION WE CAN
TALK ABOUT LATER AND OF COURSE
MULTIPLE OTHER CONSIDERATIONS
THAT I WON'T HAVE A CHANCE TO
TALK ABOUT TODAY.
VERY BRIEFLY I WANTED TO TALK
ABOUT BASELINE CONSIDERATIONS
AND CONSCIOUS EXPERIMENTS.
WHEN WE FIRST STARTED STUDYING
DS65DN WE HAD TO BE MORE
FLEXIBLE ABOUT HOW WE WERE GOING
TO COMPARE BASELINE BECAUSE
TYPICALLY WE'D PUT AN ANIMAL IN
THE CHAMBER OVER HERE.
AND EITHER PUT IT ON MULTIPLE
DAYS LIKE THREE OR FOUR DAYS AND
EVENTUALLY ACCLIMATE OR HA B
HABITU
HABITUATE.
WE DID NOT FIND THE CASE FOR
TS65DN AND HAD TO FIND ANOTHER
ALTERNATIVE AND LOOKED AT A
SMALLER SEGMENT OF BASELINE
INSTEAD OF A 10 OR 20 MINUTE
BASELINE AND FOUND A SEGMENT
CALM BREATHING IN THE LIGHT AND
DARK CIRCLE AND FELT THAT WAS
APPROPRIATE BECAUSE WHEN WE
COMPARE GAS CHALLENGES OVER HERE
HOPEFULLY YOU CAN SEE FROM THE
TRACING THAT THERE'S STUDY
BREATHING COMPARABLE TO THE CALM
BREATHING.
IT'S IMPORTANT TO RECOGNIZE
WHATEVER OUR BASELINE MEASURES
ARE TO FULLY CLARIFY THEM AND
COMPARE ACROSS GROUPS THE DATA
ARE SHOWING WITH THE CALM
BREATHING RATE IS LOWER COMPARED
TO THE LARGER 10-MINUTE BASELINE
AND IT'S MORE VARIABLE AND WHEN
WE COMPARE GAS CHALLENGES SUCH
AS HYPOXIA COMPARED TO THE
BASELINE STARTING AT A LOWER
BASELINE THAT PERCENT CHANGE IS
GREATER AND OBSERVED CIRCADIAN
S.
I WANT TO END WITH NORMALIZATION
CONSIDERATIONS.
HEAR THE RATE AND BLOOD PRESSURE
AND MANY OF THESE ARE DIFFERENT
IN ANIMAL MODELS OF DOWN
SYNDROME AND INDIVIDUALS WITH
DOWN SYNDROME.
USING THE METRICS AS A TYPICAL
NORMALIZE EVER -- NORMALIZER
ACROSS MAY SHOW DIFFERENCES AND
WHEN WE NORMALIZE HERE TO THE
LOWER BLOOD PRESSURE OF COURSE
IT'S INVERTED.
I THINK IT'S IMPORTANT WE
DISCUSS THE RAW AND POTENTIAL
NORMALIZERS.
WE'VE ALSO SHOWN SMALLER HEARTS
IN TS65DN THROUGH ECHO AND LESS
VENTRICULAR ANTERIOR WALL
THICKNESS AND POSTMORTEM AND IF
WE NORMALIZE TO BODY WEIGHT I
WOULD FIRST OFFER I THINK THAT
WAS APPROPRIATE SINCE THIS WAS A
BODY WEIGHT BY STRAIN
INTERACTION.
THESE TWO WERE CHANGING
DIFFERENTLY.
BUT ALSO THERE'S A LOT TO
CONSIDER IN THE SCENARIO.
IF THE MICE ARE BORN SMALLER AND
STAY SMALLER THEIR WHOLE LIVES
MAYBE IT'S TYPICAL TO HAVE
SMALLER HEARTS AND SOME HAVE
SIMILAR WEIGHTS AT YOUNG AGES
AND THEN LOSE WEIGHT OVER TIME
SO POTENTIALLY THEIR PHYSIOLOGY
AFFECTING THE WEIGHT LOSS AND
POTENTIALLY MUSCLE MASS LOSS AND
OTHER LEAN MASS ISSUES.
WE'RE NOT THE ONLY GROUP
CONCERNED ABOUT NORMALIZING FOR
CARDIOVASCULAR VARIABLES.
THIS IS AN EXTENSIVE
PUBLICATION.
I RECOMMEND IT FOR NORMALIZING
FOR WEIGHT AND THIS FOR SICKER
ANIMALS AND A LOT OF THEIR WORK
WAS DONE IN HEALTHY YOUNG
ANIMALS.
AND THEY RECOMMEND USING TIBIAL
LENGTH CUBED AS A MODEL IN
HEALTHY YOUNG MICE TO HELP
NORMALIZE ACROSS HEART WEIGHT.
SO SUMMARIZE, MOUSE MODELS OF
WEIGHTS AND ANY WAY TO
STANDARDIZE CAN HELP WITH
REPORTING INFORMATION AND
HOUSING CONDITIONS CAN HELP
COMPARE ACROSS GROUPS AND THE
CHOICE OF BASELINE CAN INFLUENCE
HOW THE RESPONSE IS QUANTIFIED
AND PERHAPS LATER WE CAN TALK
ABOUT POTENTIAL APPROPRIATE
NORMALIZERS FOR PHYSIOLOGICAL
DATA SETS IN DOWN SYNDROME.
AND I'D LIKE TO THANK MANY OF MY
COLLABORATORS AND MOST OF THE
WORK WAS PERFORMED BY
UNDERGRADUATES AS WELL SO THANK
YOU.
>> WE'LL HAVE OUR NEXT PANELIST.
>> THANK YOU SO MUCH.
SORRY FOR THE TROUBLE FOR THE
SLIDES.
IT MADE SENSE FOR THIS TO GO
AFTER THE MODELS HAVE BEEN
EXPLAINED ALREADY.
AND SO I AM VERY HAPPY TO TALK
TODAY ABOUT OUR EXPERIENCE WITH
DIFFERENT MOUSE MODELS OF DOWN
SYNDROME AND I THOUGHT I'D START
WITH A CHEESEBURGER FIRST.
THE McDONALD'S CHEESEBURGER IS
KNOWN FOR BEING THE SAME EVERY
TIME YOU BUY ONE.
AND NOR A LONG TIME THAT'S HOW I
CONSIDERED AND I THINK MANY
OTHERS CONSIDERED MOUSE MODELS
OF DOWN SIN -- SYNDROME AND WE
CONSIDERED THEM TO BE LIKE THE
PREVIOUS SHIPMENT OF MICE THAT
WE HAD RECEIVED AND WHAT I WILL
TELL YOU ABOUT TODAY ARE A
COUPLE STORIES WHERE WE FOUND
THIS NOT TO BE THE CASE.
THERE IS PHENOTYPIC WE
IDENTIFIED OVER TIME AND THEN I
WILL SHOW YOU ALSO THIS IS TRUE
IN TV MAC 21 WE THINK AND THEN
GO FROM THERE TO TELL YOU ABOUT
NEW DATA WE'VE DEVELOPED IN THIS
NEWER MOUSE MODEL OF DOWN
SYNDROME.
TS65DN WAS CREATED IN 1990 AND
IN 2007 WE PUBLISHED A PAPER
THAT DEMONSTRATED THE PRENATAL
BRAIN CHARACTERISTICS OF THIS
MOUSE MODEL OF DOWN SYNDROME.
ONE OF THE BIGGEST PHENOTYPES
WAS THIS VERY APPARENT DELAY IN
GROWTH OF THE CEREBRAL WALL
COMPARED TO CONTROL ANIMALS OVER
THE COURSE OF NEURO GENESIS WITH
PRENATAL DEVELOPMENT.
YOU CAN SEE THIS CLEARLY HERE.
AFTER THAT POINT THE TS65DN WAS
SPLIT INTO TWO.
THE ORIGINAL WAS THE 1924 LINE
AND A NEW LINE, 5252 WHICH HAD
BEEN CORRECTED FOR A GAIN
MUTATION THAT CAUSED RETINAL
BLINDNESS IN TS65DN.
THE 5252 LINE WAS ABLE TO BE
USED EFFECTIVELY FOR BEHAVIOR
AND THINGS LIKE THAT.
ONE OF THE THINGS WE NOTICE THE
BY CHANCE HAVING GONE BACK AND
LOOKING AT PRENATAL BRAIN GROWTH
IN THE ANIMALS AFTER THEY HAD
BEEN MAINTAINED FOR QUITE SOME
TIME IS WE HAVE LOST THIS BRAIN
DEVELOPMENTAL PHENOTYPE.
AND YOU CAN SEE THIS HERE THE
MEASUREMENT OF PORTIONS OF THE
NEOCORTICAL WALL IN THE 5252
LINE AND THICKER THAN THE
EUPLOID CONTROL.
SOMETHING DRASTIC CHANGED IN THE
MOUSE AND WE ASKED THEM TO
RECOVER SOME FROZEN EMBRYOS THEY
BANKED WHEN THEY MADE THE 5252
LINE AND THIS IS THE BLUE BOX
THE CRYO 2010.
YOU CAN SEE THE CORTICAL
DEVELOPMENTAL PHENOTYPE WAS
PRESENT IN THOSE ANIMALS THAT
HAD BEEN FROZEN AT THE ORIGINAL
STATE.
OVER THIS TYPE THERE HAS BEEN A
CHANGE IN THIS VERY MAJOR BRAIN
DEVELOPMENTAL PHENOTYPE.
THAT'S POINT NUMBER 1.
THE FACT THIS CAN HAPPEN.
AND MORE RECENTLY WE'VE BEEN
EVALUATING BRAIN DEVELOPMENT IN
MAC 21 AND THERE'S AGAIN A LONG
ARM OF HUMAN CHROMOSOME 21 IN
THE CELLS AND ALSO HAS A NIFTY
GFP LOCUS ADDED AND YOU CAN SEE
THE GREEN FLUORESCENT TRISOMIC
ANIMALS HERE.
WE HAVE BEEN CHARACTERIZING
THESE ANIMALS FOR EARLY BRAIN
DEVELOPMENT UP TO ADULTHOOD
MEASURING BRAIN GROWTH AND
DIFFERENT ASPECTS OF CELL
PROLIFERATION AND SUCH.
WHAT WE HAVE FOUND FROM OTHER
ANIMAL MOUSE MODELS IS THERE'S
NO CHANGE IN SIZE OF THE EMBRYOS
OR IN GROWTH OF THE BRAIN OVER
TIME.
IN FACT, IF YOU LOOK AT CORTICAL
WALL THICKNESS HERE DURING
PRENATAL DEVELOPMENT THERE'S NO
DIFFERENCE BETWEEN TRISOMIC AND
OOUP -- EUPLOID CONTROLS AND
THIS IS DIFFERENT FROM A RECENT
PAPER THAT CAME FROM THE GROUP
IN JAPAN WHO HAVE ANALYZED
DEVELOPMENT IN TC MAC 21 AND
THEY SEE DIFFERENCES IN NEURONAL
PRODUCTION IN PRENATAL
DEVELOPMENT AN THERE'S DIFFERENT
FINDINGS IN LABS AROUND THE
WORLD STUDYING THE SAME MOUSE.
ONE OF THE THINGS THAT MAY PLAY
A ROLE IN THIS IS THAT THE
ANIMAL WAS FIRST GENERATED IN
JAPAN AND HAD A PERIOD OF TIME
WHERE TRANSFER TO THE UNITED
STATES WAS A BIT DIFFICULT AND
SO WHAT HAPPENED IN THE END THE
JAPANESE TEAM CREATED A BUNCH OF
FROZEN EMBRYOS FROM FEMALES AND
TRANSLATED THEM TO JACKSON LABS
AND THOSE WERE RECOVERED AND
DISTRIBUTED OUT TO INVESTIGATORS
IN THE UNITED STATES.
THIS IS POTENTIALLY AN AREA
WHERE THE ANIMALS MAY HAVE
DIVERGED TO CREATE DIFFERENCES
IN THE PHENOTYPES BETWEEN THOSE
THAT ARE HOUSED IN JAPAN NOW AND
THOSE BEING SUPPLIED IN THE
UNITED STATES.
SO IT'S JUST SOMETHING TO BE
AWARE OF.
TO MAKE SURE WE STUDY THESE
ANIMALS CAREFULLY ENOUGH TO
QUANTITATIVELY UNDERSTAND WHAT'S
HAPPENING AND COMPARE THEM TO
OUR COLLEAGUES.
THE ANIMALS ARE NOT ALL VARIABLE
IN ALL DIFFERENCE.
IN FACT IT TURNS OUT THERE'S
SOME VERY IMPORTANT SIMILARITIES
SEEN IN ALL MOUSE MODELS OF DOWN
SYNDROME AND REPLICATED IN HUMAN
POSTMORTEM SAMPLES AS WELL.
THAT HAS TO DO WITH THE CELLULAR
PROLIFERATION OF THE NEURAL
PRECURSORS AS THE BRAIN
DEVELOPS.
AS YOU ALL PROBABLY KNOW IN THE
DEVELOPING BRAIN PARTICULARLY IN
THE CORTEX, THE MAIN STEM CELL
IS CALLED THE RADIO GLIAL CELLS
AND DIVIDE TO CREATE THE
EXCITATORY NEURONS DURING
PRENATAL DEVELOPMENT.
THEY DON'T DO THIS ALONE THEY
HAVE OTHER BASAL AND
INTERMEDIATE PROGENITORS THAT
ALSO DIVED TO MAKE THESE AND
IT'S THE SUITE OF CELLS CREATING
CELLS DURING PRENATAL
DEVELOPMENT.
WHAT WE FOUND IN TS65DN THE
INTERMEDIATE PROGENITORS WITH
THE MARKER DIVIDING OUT HERE
AWAY FROM THE SURFACE OF THE
VENTRICLE IS DRASTICALLY REDUCED
THIS BRAIN COMPARED TO EUPLOID
AND THEY EXPRESS THE
TRANSCRIPTION FACTOR T BRAIN 2
OR TBR2 RED IN THE IMMUNOSTAIN.
YOU CAN SEE THE NUMBERS OF THESE
PROGENITORS IS DECREASED IN
TS65DN CORTEX ALSO WITH THIS
MARKER AND THE QUANTIFICATION IN
THE RIGHT.
YOU SEE THE DECREASE IN THE
INTERMEDIATE PROGENITORS AND THE
MITOTIC FIGURES OF THE CELLS IN
C2.
THE SAME PAPER I WAS REFERENCING
MEASURED THIS AND THEY SHOW A
SIGNIFICANT DIFFERENCE OR
DECREASE IN THESE BASAL
PRECURSORS DURING PRENATAL
DEVELOPMENT AND YOU SEE THAT
QUANTIFICATION HERE.
TOGETHER THE TWO MOUSE MODELS
AND DP16 AND OTHER AS WELL HAVE
DEMONSTRATED ABNORMALITIES IN
PRECURSOR DEVELOPMENT AND THIS
MAY BE A COMMON THEME IN
PRENATAL BRAIN DEVELOPMENT ALSO
IN PEOPLE WITH DOWN SYNDROME.
TO LOOK MORE CAREFULLY AT THE
BASAL PRECURSORS WE'VE USED IN
UTERO ELECTROPROLIFERATION TO
DELIVER TOOLS TO LOOK AT THE
BASAL INTERMEDIATE CELLS AND
CONTRAST THEM FROM THE STEM
CELLS.
AND SO THIS TECHNIQUE INVOLVED
GENERATING GENE CONSTRUCTS
INJECTING THEM DIRECTLY INTO THE
FETAL BRAIN AND TRANSFECTING
THEM IN THE NEOCORTICAL WALL IN
THE C2.
IF WE ADD THE CELLS WE FIND THE
RADIAL GLIAL CELLS WILL HAVE
BLUE REPRESENTED IN GREEN HERE
IN THE SLIDES WE CAN DETERMINE
THE NUMBER OF PRECURSOR CELLS.
WHAT WE FOUND QUICKLY IS IN THE
CONTROL BRAINS WE FIND ABOUT 60%
ARE PROGENITORS AND IN TC MAC 21
IT'S OPPOSITE THERE'S 60% RADIO
GLIA AND FEWER INTERMEDIATE
PROGENITOR CELLS.
IN THE NEXT SLIDE I'LL SHOW
ANOTHER EXPERIMENT.
WE USED THE SAME TECHNIQUE TO
ASK IF THE TC MAC HAD FEWER OF
THE BASAL PROGENITORS WHAT'S
THIS MEAN IN TERMS OF PRODUCTION
OF THE NEURONS THEY'RE IT
GENERATE IN THIS EXPERIMENT SAME
TOOLS AND WENT TO POST NATAL DAY
21.
WE FOUND IN THE CONTROL BRAINS,
THE NUMBER OF NEURONS DERIVED
FROM THE RADIO GLIAL CELLS IS
50% AND 50% FROM THE IMMEDIATE
PROGENITORS AND IN THE TRISOMIC
FEWER COME FROM THAT TYPE OF
PROGENITOR.
MOST COME FROM THE RADIO GLIAL
CELLS.
THE CORTEX IS BUILT GENERALLY
THE SAME WAY BUT ENDS UP WIN
NEURONS WITH A SLIGHTLY
DIFFERENT MIX OF PRODUCTIONAL
STREAMS AND WE THINK THIS MAY BE
VERY IMPORTANT IN HOW THE
CIRCUITRY DEVELOPS AFTER THAT.
QUICKLY, TAKE HOME MEASURES.
SOME TAKE-HOME MESSAGES.
MOUSE MODELS OF DOWN SYNDROME
SHOULD NOT BE CONSIDERED STABLE
BY DEFAULT THEY SHOULD BE
CRITICALLY ANALYZED IN THE LAB
WHEN THEY'RE RECEIVED.
AND ALSO IT SEEMS LIKE THERE'S
BEEN POTENTIAL RESTRICTION
EVENTS IN TERMS OF THE TC MAC 21
LINE COMPARED FROM THOSE
EXISTING IN JAPAN AN THOSE THAT
ARE NOW PRODUCED IN THE USA.
THIS CLEARLY IDENTIFIES THE NEED
FOR HIGH AMOUNT OF RIGOR WHEN
USING THE ANIMALS FOR
EXPERIMENTS.
AND LASTLY, SOME OF THE NEWER
DATA ON NEURO PROGENITOR ON
PROLIFERATION SUGGESTS INDIRECT
NEURAL GENESIS FROM THE BASAL
CELLS IS DECREASED IN THE ANIMAL
MODELS OF DOWN SYNDROME AND
WE'RE INTERESTED HOW THE
SPECIFIC CHANGE DURING EMBRY ON
IC DEVELOPMENT CAN CHANGE --
EMBRYONIC DEVELOPMENT CAN LEAD
TO CHANGES IN BRAIN STRUCTURE
AND I'LL STOP AND THANK TRISH,
JENNY AND JOE FOR THEIR GREAT
WORK AND NICHD FOR THEIR GREAT
FUNDING.
>> TESTING THE MIC.
SO NOW IT'S THE OPPORTUNITY IF
ANYONE IN THE AUDIENCE HAS SOME
OF THEIR LIVED EXPERIENCES THAT
YOU WANT TO ADD TO THE
DISCUSSION OR HAVE QUESTIONS FOR
ANY OF THE PANELISTS, PLEASE
COME UP TO THE MIC AND WHILE
WE'RE WAITING FOR PEOPLE TO COME
UP, DO ANYTHING PANELISTS HAVE
QUESTIONS FOR EACH OTHER?
>> I THINK THIS IS A GREAT THING
TO HAVE DONE BECAUSE MANY OF US
IN THE AUDIENCE ARE EXPERIENCING
WHATEVER END ORGAN WE MIGHT BE
LACKING AT AT THE SAME KIND OF
THING.
I'M A SIMPLE BONE HEAD SO WHAT
SHOULD WE BE DOING?
SHOULD WE BE BOTHERING TO BREED
THESE MICE BUT I THINK THERE'S
ISSUES ON JAX AS WELL AND
CURIOUS WHAT ANYONE THINKS OR
SHOULD WE JUST KEEP ADDING TO
THE DIVERSITY AND PHENOTYPIC
VARIATION FROM TEXAS TO WHEREVER
THE HELL ELSE THE MICE ARE.
>> IT BRINGS UP ANOTHER ISSUE
THAT OUR SAMPLE SIZE HAS TO BE
LARGE ENOUGH TO DETECT THESE
TYPES OF VARIATION.
WHEN I SEE SAMPLE SIZE OF THREE
AND FOUR I CRINGE.
THERE'S VARIABILITY.
>> IT'S RELATED TO THE SIZE OF
THE DIFFERENCE, RIGHT?
>> THAT'S RIGHT.
AND DO WE HAVE ENOUGH POWER TO
DETECT THE DIFFERENCE AND HAVE
TO BE CAREFUL WHAT WE'RE DOING
THERE.
NOT WITHSTANDING THE OTHER
ISSUES WITH YOU CAN HAVE 20 OF
THE TC MAC 21 MOUSE THAT NOW
YOU'RE GETTING FROM JACKSON MAY
BE DIFFERENT FROM THE ONES THEY
ORIGINALLY BRED IN JAPAN.
>> THANK YOU.
>> HELLO.
KELLY SULLIVAN THE SERNIC
INSTITUTE.
THANK YOU FOR THE EXPERIMENTAL
CONDITIONS BUT GIVEN THE
INTEREST IN THE TC MAC 21
WONDERING WHAT YOU THINK OF THE
TRISOMIC UTERINE DEVELOPMENT IN
EARLY DEVELOPMENTAL PHENOTYPES?
>> I TRY NOT TO THINK ABOUT IT
AT ALL.
IT'S A BIG FACTOR AND SOMETHING
WE HAVE TO KEEP IN THE
BACKGROUND AS A FEATURE OF HOW
RELEVANT WHAT WE'RE DOING
ACTUALLY IS FOR PEOPLE THAT DID
NOT DEVELOP TRISOMIC.
GOOD POINT.
>> I THINK IT ALSO DEPENDS ON
WHAT PHENOTYPE YOU'RE LOOKING
AT.
WE LOOKED AT SIZE OF EMBRYOS AND
SHOWED THE UTERINE ENVIRONMENT
DIDN'T HAVE A DIFFERENT
INFLUENCE BUT THAT WAS SAMPLING
A SIMPLE PHENOTYPE.
>> I JUST WANTED TO MENTION THAT
WE RECEIVED SOME DIRECTLY FROM
JAPAN SO THE MICE WE RECEIVED
MAY BE THE ORIGINAL.
IT'S A LONG STORY.
WE PUT XIST INTO THOSE AND THE
ONES WE DID PUT IT INTO ARE
STILL BREEDING.
THE OTHERS STARTED HAVING
TROUBLE BREEDING BUT WE'VE HAD
TO FREEZE SOME AND HAD TO
RECONSTITUTE IN CASE THAT'S
HELPFUL TO ANYONE.
AND SORRY TO PUSH THE IDEA BUT I
WISH SOMEBODY ELSE WOULD HELP DO
IT.
IF YOU HAD THE ABILITY TO
SILENCE THE CHROMOSOME MAYBE
EVEN INDUCIBLY IN THE SAME MOUSE
MODEL, THEN YOU WOULD KNOW THAT
WHATEVER CHANGE YOU SAW WAS DUE
TO THE CHROMOSOME AND IF ANYONE
WANTS TO TRY THAT, I'LL HELP
THEM.
>> I SECOND THAT.
I THINK THAT'S AN EXCELLENT
SUGGESTION.
I'M FROM UNIVERSITY OF CHICAGO
AND I'VE BEEN A HEART DISEASE
PERSON FOR DECADES AND THE
STRUCK BY THE VARIABILITY IN THE
LITERATURE OF PEOPLE REPORTING
THE SAME WITH DIFFERENT
PHENOTYPES AND DIFFERENT
EXPRESSIVITY.
WE LIKE TO DO QUALITATIVE
SCIENCE.
AND MAYBE DOWN SYNDROME WE NEED
TO THINK OF AS A SUBTLE CHANGE
GENETICALLY ONLY 50% INCREASE IN
THE GENES THAT ARE THERE.
THIS IS A KNOCKOUT.
WE SHOULDN'T EXPECT SIMILAR
PENETRANT OR EXPRESSIVITY AND IF
WE CHANGE OUR VIEW TO A MORE
QUANTITATIVE VIEW AND
COMMUNICATE MORE OPENLY ACROSS
BOUNDARIES TO ASSESS MODELS BY
MULTIPLE GROUPS MAYBE WE CAN
CORRECT SOME PROBLEMS IN THE AND
STOP PUBLISHING VARIABILITY.
>> I'M FROM PAKISTAN AND THIS IS
MY SERVICE VISIT TO NIH SO I'M
EXCITED TO BE PART OF THE
CONFERENCE.
FIRST, I THINK I ENJOY THE
SESSIONS FROM THIS MORNING AND
MY QUESTION IS FROM TIFFANY.
THANK YOU FOR HIGHLIGHTING THE
BIO MEDICAL MODEL VERSUS THE
SOCIAL DETERMINATES OF HEALTH
MODEL AND COMING FROM PAKISTAN
WHERE THE RESOURCES ARE STRAINED
AND THE DISEASE BURDEN OF DOWN
SYNDROME IS HUGE AND THERE'S
DEVELOPMENTAL GOALS.
WE ALL AIM FOR ATTAINING IT BY
2030 OR SO AND WE'RE FACING
STRUGGLES AND CHALLENGES.
SO WHEN WE TALK ABOUT DOWN
SYNDROME AND I'M HEARING
RESEARCH FOR DOWN SYNDROME AND
HOW DO WE FORESEE INCLUSIVENESS
OF DOWN SYNDROME FROM THE LMICs
AND FROM THE RESEARCH SPECTRUM
WHERE WE HAVE LIMITED RESOURCES
FOR RESEARCH AND CONSIDERING WE
HAVE OF COURSE LIMITED RESOURCES
BUT TO A CERTAIN EXTENT WE DO
HAVE AT NIH.
HOW DO WE FORCE INCLUSIVENESS OF
DOWN SYNDROME FROM THAT PART OF
THE WORLD WHERE WE CAN
CONTRIBUTE TO ONE-THIRD OF THE
WORLD'S POPULATION.
>> THANK YOU FOR THAT QUESTION.
IT'S A BIG, BIG, BIG, QUESTION.
AND THE COMPLEXITY OF ENGAGING
WITH ALL OF THE DIFFERENCES AND
THE TYPES OF RESOURCES AVAILABLE
TO SUPPORT DIFFERENT INDIVIDUALS
AROUND THE WORLD, IT'S A
STAGGERING PROBLEM.
I DON'T HAVE IDEAS ABOUT
SOLUTIONS BUT I THINK WHAT WE
WOULD LIKE TO SEE IS MAKING SURE
INPUT FROM ALL THE STAKEHOLDERS
ACROSS THE WORLD AND THE
DIFFERENT CIRCUMSTANCES IS
ACCESSED AND TAKEN INTO
CONSIDERATION.
I THINK THE THING THAT WORRIES
ME A LOT IS FOR THE INDIVIDUALS
WHO HAVE THE LEAST ACCESS TO
RESOURCES AND MAYBE TO THE
HIGHEST SUPPORT NEEDS MAY HAVE
THE FEWEST OPPORTUNITIES TO
CONTRIBUTE THEIR VOICE TO THE
CONVERSATIONS ABOUT WHAT SHOULD
BE RESEARCH PRIORITIES AND HOW
DO WE IDENTIFY FUNCTION LEVELS
WHEN WE'RE WANTING TO INCLUDE
INDIVIDUALS WHO COME FROM SO
MANY LIFE EXPERIENCES WITH SO
MANY LEVELS OF SUPPORT THAT WILL
ULTIMATELY IMPACT HOW PEOPLE
PERCEIVE THEIR FUNCTIONING
LEVELS?
IT'S A BIG CONVERSATION AND I
LOOK FORWARD FOR THE COMMUNITY
TO CONTINUE TALKING ABOUT THIS
IN THE COMING YEARS.
>> GREAT TALKED.
I'M FROM NYU SCHOOL OF MEDICINE.
MICE SHOULD ALL BE BRED BACK TO
A BLACK 6 TO KEEP IT ISO GENIC
AND DIVERSITY ISN'T BAD AND
HUMANS ARE DIVERSE.
SHOULDN'T WE TRY TO MAP THE
MODIFIERS BETWEEN THE DIVERGENT
THINGS THAT ARE HELPFUL AND
STRAINS AND IT'S AN OPPORTUNITY
TO LOOK AT THE MODIFIERS?
>> I THINK THE FIRST THING WE
HAVE TO THINK ABOUT IS NOT ALL
THESE MICE ARE ON AN INBRED
BACKGROUND AND IT OFFERS
ADVANTAGES AND DISADVANTAGES.
LIKE WE SAID BEFORE WE NEED TO
THINK ABOUT THIS MORE AS A
QUANTITATIVE TRAIT THAT IS NOT
PRESENT OR ABSENCE AND I THINK
WHEN YOU START LOOKING AT THAT
AND START THINKING ABOUT WHAT
ARE THE MODIFIER GENES ON THE
CHROMOSOME AS WELL AS DIFFERENT
CHROMOSOMES.
>> I WOULD LIKE TO ADD FIRST
THAT I THINK JAX IS AMAZING.
I THINK WHAT THEY DO IS
DIFFICULT AND I THINK THEY
EXPERIENCE MANY OF THE
CHALLENGES THAT WE DO AND TRYING
TO DO IT IN A CONTROLLED WAY AND
WANTED TO PUT THAT OUT THERE.
IN TERMS OF THE VARIABILITY,
IT'S A DOUBLE-EDGED SWORD.
IT'S GREAT FOR WET LAB SCIENTIST
TO STUDY SOMETHING CONSTANT OVER
TIME AND DEVELOP A QUANTITATIVE
INFORMATION OF IT.
THE FACT THAT MANY OF OUR MODELS
ARE NOT THAT ARE THAT'S AN
IMPORTANT FEATURE.
WE NEED TO BE ABLE TO DO OUR
WORK CAREFULLY ENOUGH SO WE CAN
DO THAT WELL.
>> I'M THERE THE JACKSON LAB,
CHING RALPH --
[APPLAUSE]
BUT I HAVE NOTHING TO DO WITH
THE PRODUCTICTION OF THE MICE WE
TALKING ABOUT.
>> DID I SAY IT RIGHT.
>> I'LL BRING THIS BACK.
I'M ACTUALLY A PEDIATRIC
ONCOLOGIST STUDYING TAM IN DOWN
SYNDROME.
I HAVE A QUESTION FOR THE PANEL.
IS THERE EXISTING DATA COMPARING
THE HEMATOLOGIC PROFILE OF THE
MOUSE MODELS FOR DOWN SYNDROME?
BECAUSE THAT MAY BE VERY
CRITICAL FOR US TO USE THEM AS A
STARTING POINT TO STUDY TAM.
>> WE'VE RECENTLY SHOWN HE MATIC
CONCENTRATIONS ARE LOWER AND WE
FOLLOWED THAT UP IN A POPULATION
MEDICAL RECORD REVIEW AND FOUND
ANEMIA IS ALSO VERY COMMON IN
INDIVIDUALS WITH DOWN SYNDROME
BUT WE HAVE SHOWN IT IN MT65DN
THE LEVELS ARE LOWER.
>> WHEN YOU START COMPARING THE
DIFFERENT DOWN SYNDROME MOUSE
MODELS, THEY'RE ALWAYS
GENERATING NEW MODELS.
THERE'S A COUPLE MODELS WE'RE
EXCITED ABOUT TC MAC WE'RE
TRYING TO GENERATE THE DATA AND
COMPARE THEM WHERE WE HAVE THE
DATA.
I THINK WE HAVE BONE PHENOTYPES
FROM PROBABLY 12 DIFFERENT MOUSE
MODEL.
THE STUDY I SHOWED YOU WAS NINE
DIFFERENT MOUSE MODELS.
WE'RE STARTING TO MAKE THOSE
TYPES OF COMPARISONS BETWEEN THE
MODELS.
>> JULIE CORNBERG UNIVERSITY OF
UTAH.
THANK YOU FOR THE WONDERFUL
PRESENTATION.
AS A GENETICIST VARIATION IS OUR
FRIEND NOT OUR ENEMY AND WE
EXPLAINED THIS IN TERMS OF
EXPRESSIVITY AND VARIATION OF
THINGS.
IN FACT, I THINK THERE MAY BE
EQUAL OR GREATER VARIABILITY IN
HUMANS AND THEREFORE THIS MAKES
ME FEEL VERY GOOD ABOUT MOUSE
MODELS TO SEE WE HAVE SUCH
VARIATION.
AND I'D LIKE TO KNOW YOUR
THOUGHTS AND PERHAPS YOU'VE
ADDRESSED THIS MOST STRIKINGLY.
HOW CAN WE USE THIS OR
STANDARDIZE IT OR PROVIDE
INFORMATION IN PAPERS ABOUT WHAT
THE TEMPERATURES OR GENDERS AND
VARIOUS THINGS THAT WERE
DISCUSSED TO USE VARIATION IN
THE MOUSE MODELS TO UNDERSTAND
AND POSE TOWARDS HUMANS.
>> THANK YOU FOR ALL YOUR KIND
COMMENTS ABOUT OUR
PRESENTATIONS.
YEAH, I THINK FINDING A WAY TO
STANDARDIZE OR AT LEAST
STANDARDIZE WHAT IS REPORTED IN
A METHODS SECTION.
>> THAT'S THE ISSUE.
WE'LL NEVER STANDARDIZE, THANK
GOD.
>> BUT WHAT IS REPORTED I THINK
WOULD BE VERY VALUABLE TO THE
COMMUNITY SO WE COULD COMPARE
ACROSS GROUPS.
>> I AGREE.
I THINK WE NEED TO THINK ABOUT
PROVIDING AS MUCH DETAIL AS
POSSIBLE IN OUR PUBLICATIONS
INCLUDING WHEN WE RECEIVED
ANIMALS FROM WHOM, HOW MANY
TIMES THEY WERE BRED, THE
GENERATION STATUS OF THE ACTUAL
SAMPLES THAT ARE IN THE GRAPHS.
WIRE CAGES FOR -- THERE'S SO
MUCH THAT WE NEED TO I THINK
ABLE TO CAREFULLY AND COMPLETELY
DISSEMINATE ALONG WITH THE DATA
SO THAT BECAUSE ALL OF THAT
INFORMATION ALTOGETHER WILL BE
KNEADED TO COMPREHENSIVELY
REPEAT THOSE STUDIES.
>> IF I CAN JUST MAKE A COMMENT
HERE THAT IT'S VERY EXCITING TO
SEE THAT PERHAPS THE KIND OF
VARIATION YES, HEART DISEASE,
NO, HEART DISEASE, SMALL, LARGE,
WHATEVER IS REALLY -- GIVES A
GREAT HOPE FOR OUR HUMAN STUDIES
BECAUSE IT MEANS THAT WITH VERY
SMALL CHANGES, PERHAPS
ENVIRONMENTAL IN SOME CASES, WE
MAY BE ABLE TO PREVENT, TREAT,
ETCETERA HUMANS INSTEAD OF THINK
OH, MY GOD THERE'S A GENE 80% X.
I THINK IT'S VERY IMPORTANT WE
UNDERSTAND THESE KINDS OF THINGS
IN THE MOUSE AND PERHAPS TRY TO
UNDERSTAND THEM A LITTLE BIT IN
HUMANS.
>> I'M HAVE THE UNIVERSITY OF
TEXAS SOUTHWESTERN MEDICAL
CENTER.
I'M HERE TO CONFESS MY SINS AND
I'M TRYING TRYING -- TO LOOK AT
F1s AND WONDERING WHAT YOU THINK
ABOUT THAT.
>> I THINK IT CERTAINLY HAS
MERIT AS LONG AS YOU'RE TRACKING
THE VARIABILITY YOUR E INTRO
INTRODUCING AND WOULD MORE
CLOSELY MODEL THE SYSTEM AND HOW
MANY MICE YOU'D NEED TO SEE THE
PHENOTYPE --
>> WE WERE CONCERNED INITIALLY.
AS LONG AS WE'RE MAINTAINING THE
DP16.
WE MAINTAIN THOSE AS RELATIVELY
DP16 PURISH AND MAKE THEM TO A
CD 1 AND LOOK AT THOSE
PHENOTYPES AND STILL MAINTAINED
PHENOTYPE.
JUST THROWING IT OUT THERE.
>> THANK YOU FOR THE PANEL.
I'M CONTINUING ON THE THEME OF
DIVERSITY ACTUALLY BEING A GOOD
THING.
I WANT TO PUT A NOTE OF OPTIMISM
HERE AND THERE'S SOME PHENOTYPES
VERY REPRODUCIBLE.
DP16 MICE HAVE COGNITIVE
DEFICITS.
HALF OF THOSE HAVE ISSUES AND
THERE'S VARIABILITY BUT I THINK
WE CAN AGREE ON CORE PHENOTYPES
OF RELEVANCE TO THE HUMAN
CONDITION THAT ARE SEEN TIME AND
TIME AGAIN.
START FROM THAT POINT WHAT DO
YOU THINK SHOULD BE THE KEY BIG
VARIABLES WE SHOULD TRY TO MODEL
IN THE LAB AND LOOKING AT A MORE
SOCIAL ENVIRONMENT.
IS THAT THE FIRST THING WE NEED
TO UNDERSTAND AND SOMETHING THAT
COMES TO MIND IS DIET.
PEOPLE WITH DOWN SYNDROME DON'T
EAT THE BIG MACS.
AND WHAT OTHER VARIABLES SHOULD
WE TRY TO BRING IN IN A
SYSTEMATIC FASHION TO UNDERSTAND
THE IMPACT ON THE CORE
PHENOTYPES.
IF YOU ASK ME I'LL SAY WE NEED
TO TRACE THE MICE WITH REAL LIFE
PATHOGENS.
I WANT TO HEAR YOUR IDEAS.
>> SO AS A GENETICIST MOST
PEOPLE WITH DOWN SYNDROME HAVE
AN EXTRA CENTROMERE.
THERE'S ONE VARIABLE WE HAVE AND
THERE'S WORK THAT SHOWS THERE'S
AN EFFECT OF THAT.
SO AND MY COLLEAGUES HERE HAVE
INSIGHT IN THE ENVIRONMENTAL
EFFECTS.
>> WE START WITH THE ARRIVE
GUIDELINES, I THINK ACRONYM
A-V-R-E AND REPORT TIME OF DAY
IN OUR EXPERIMENTS.
I FEEL DIET WOULD HAVE A HUGE
IMPACT OF THE COMPOSITION OF THE
DIET AND TEXTUAL ASPECTS OF THE
FOOD PELLET AND TEMPERATURE AND
HOUSING AND SOMETIMES MICE CAN
BE CO-HOUSED AND SOMETIMES NEED
TO BE SINGLY HOUSED.
ISSUES LIKE SOCIAL STRESS SEEM
TO HAVE A HUGE IMPACT ON
OUTCOMES FOR THE TS65DN AS THEY
START TO AGE AND GET VERY OLD.
SOCIAL STRESS CAN IMPACT THEM
HEAVILY TO KNOW WHAT OTHER --
>> I AGREE WITH TO THE HOUSING
CONCERNS.
ANY WAY TO REPORT WHAT WE CAN DO
IN OUR STUDIES TO COMPARE ACROSS
GROUPS IS HELPFUL.
WE FIND THE SAME THING WITH
AGING TO65DN AS THEY GET OLDER
THE SOCIAL STRESS SEEMS TO BE
MORE PROBLEMATIC.
WE SEPARATE THEM AT THE END
POINT HOW DOES THAT INTRODUCING
VARIABILITY BUT THERE'S SOME
THINGS YOU CAN'T CHANGE.
IF YOU'RE AT AN FACILITY WITH
IVE SYSTEM YOU CAN'T GO TO A
WERE TOP CAGING SYSTEM AN
THERE'S SOME ISSUES OUTSIDE OF
OUR CONTROL IN CERTAIN
SCENARIOS.
THERE'S A LOT TO CONSIDER AND AS
A COMMUNITY WE CAN THINK ABOUT
SOME THINGS THAT ARE THE MOST
IMPORTANT AND I'LL ECHO THE DIET
CONCERNS AND TALK ABOUT IN UTERO
AND WHEN DOES A NEW DIET GET
INTRODUCED.
THERE'S ALL KINDS OF DIETS THAT
CAN INFLUENCE OUTCOMES AND THE
TYPICAL CHOW DIET IS LOW FAT NOT
NECESSARILY DIRECTLY COMPARABLE
TO HUMAN DIET.
AT LEAST AN AMERICAN DIET.
>> WE'LL HAVE TO BRING THE PANEL
TO A CLOSE AND APOLOGY FOR THE
QUESTIONS WE DIDN'T HAVE TIME TO
ADDRESS.
THE NEXT ITEM IN OUR AGENDA IS
TO INTRODUCE THE BREAKOUT
SESSIONS.
>> MY NAME IS MEGAN O'NEAL.
I'M A NEW PROGRAM OFFICER,
MEDICAL OFFICER FOR THE INCLUDE
PROJECT.
FOR THE DEVELOPMENT AND
DISABILITIES BRANCH.
I'M TRAINED AS A NEURAL
DEVELOPMENTAL PHYSICIAN AND
CHILD NEUROLOGIST.
I PROMISE NOT TO KEEP YOU TOO
MANY LONGER FROM YOUR LUNCH.
I'LL TALK BRIEFLY ABOUT BRINGING
ALL TOGETHER WITH BREAKOUT
SESSIONS HAPPENING DURING LUNCH
TODAY.
TODAY WE HEARD ABOUT THE
DIFFERENT COMPONENTS OF THE
INCLUDE PROJECT.
AND LATER WE'LL HEAR MORE ABOUT
COMPONENT 2, THE COHORT
DEVELOPMENT PROJECT THROUGH THE
LENS OF THE INCLUDE DATA
COORDINATING CENTER.
TOMORROW WE'LL HERE MORE ABOUT
THE CLINICAL TRIALS AS WELL.
I THINK THE IDEAS THAT ALL OF
THESE COMPONENTS ARE WORKING
TOWARDS SOME COMMON GOALS AND WE
WANT TO GENERATE RESEARCH TO
IMPROVE TREATMENTS AND
INTERVENTIONS FOR PEOPLE WITH
DOWN SYNDROME.
WE WANT TO IMPROVE THE QUALITY
OF LIFE FOR PEOPLE WITH DOWN
SYNDROME.
AND ULTIMATELY WE HOPE TO
IMPROVE INFORMATION OF VARIOUS
DISEASE STATES TO BENEFIT THE
GENERAL POPULATION AS WELL.
SO HOW DO WE BEST ACHIEVE
SUCCESS?
WE'LL TRY TO CONVINCE YOU CROSS
COLLABORATION WILL HELP
TRANSLATE FROM BENCH TO BEDSIDE
AND WANT TO CLOSE THE GAP TWO
SOMETIMES DIFFERENT WORLDS,
LABORATORY, BASIC SCIENCE
RESEARCH AND CLINICAL CLINICAL
MED SPIN WE HOPE TO CONNECT
RESEARCHERS ACROSS FIELDS THAT
ARE RELEVANT AND DO THIS THROUGH
SOME BREAKOUT SESSIONS.
THIS MEETING IS AN OPPORTUNITY
TO COME TOGETHER.
WARE ALL IN THE SAME PHYSICAL
ENVIRONMENT AND WE WANT TO GET
YOU GUYS TALKING.
WE WANT TO SHARE CHALLENGES AND
LESSONS LEARNED AND IDEAS TO
HELP FIGURE OUT THE FUTURE
DIRECTION FOR THE INCLUDE
PROJECT.
WE'LL HAVE BREAKOUTS AND WE'LL
HAVE NEURAL DEVELOPMENTAL 1 AND
THE SECOND GROUP IS COGNITION,
REGRESSION AND AUTISM AND ADHD
AND STRUCTURAL AND BIRTH DEFECTS
AND FOR THE IMMUNE SYSTEM
DYSREGULATION AND ONE FOR
ALZHEIMER'S DISEASE AND ONE FOR
SLEEP.
ACROSS THESE DIFFERENT AREAS, WE
WANT TO TALK ABOUT GAPS IN
SUPPORT STRATEGIES AND
DIRECTIONS TO ADVANCE THE FIELD,
WAYS TO HARNESS ARTIFICIAL
INTELLIGENCE AND EMERGING
TECHNOLOGIES AND PROMISING AREAS
OF INTEREST.
IN TERMS OF THE SESSION FORMAT
THERE WILL BE INVESTIGATOR LEADS
MODERATING THE DISCUSSION USING
PROMPTS AND QUESTION TO HELP
GUIDE THE DISCUSSION AND HAVE A
REPRESENTATIVE FROM THE NIH TEAM
IN EACH SESSION TO HELP KEEP
THINGS ON TRACK AND YOU GUYS AS
INVESTIGATORS SHOULD SELF-SELECT
TO THE TOPIC AREA THAT BEST FITS
YOUR RESEARCH INTERESTS.
WE'LL HAVE DISCUSSIONS
THROUGHOUT THE LUNCH PERIOD AND
THEN THOSE WILL ULTIMATELY BE
SUMMARIZED BY THE GROUP LEAD AND
WE'LL DO FIVE-MINUTE REPORT OUTS
TOWARD THE END OF THE MEETING.
OUR GOALS ARE TO UNDERSTAND GAPS
AND CHALLENGES THAT GET A BETTER
GRASP OF THE RESEARCH LANDSCAPE
AND WORK ON NETWORKING,
PROFESSIONAL GROWTH AND
HOPEFULLY MAKE NEW CONNECTS
BETWEEN INVESTIGATORS TO HELP
GUIDE NEW DIRECTION FOR
RESEARCH.
WE WANT TO HEAR OPINIONS ACROSS
THE BOARD.
THIS IS A LISTING OF THE
DIFFERENT ROOMS.
SO PLEASE TAKE A LOOK AT THIS
AND FIGURE OUT WHAT TOPIC BEST
REPRESENTS YOUR RESEARCH AND
WHERE YOU'LL BE GOING.
THERE WILL BE BOX LUNCHES THAT
HAVE BEEN ORDERED YOU'LL PICK UP
AND TAKE TOE -- TO THE ASSIGNED
ROOM.
ALL THESE ROOMS YOU CAN EAT AND
DRINK UNLIKE THE CURRENT ROOM.
WITHOUT FURTHER ADO I THINK
WE'RE READY TO GO.
THANK YOU, EVERYBODY.
GOOD AFTERNOON
AND I'M WITH THE NATIONAL HEART,
LUNG, BLOOD, INSTITUTE.
WE HAVE A PRODUCT SCIENTIST FOR
THE DATA DISEASE COORDINATE
CANNING CENTER.
IT'S BEEN A PRIVILEGE TO AGREE
TOGETHER WITH A GREAT TEAM AND
IT'S MY GREAT PLEASURE AND HONOR
TO INTRODUCE THE OUTSTANDING
INCLUDE DATA LEARNING CENTER
TEAM.
TODAY WE HAVE SIX SPEAKERS WE'LL
INTRODUCE ALL OF THEM TO SAVE
TIME FOR TRANSITION.
THE FIRST SPEAKER IS ESPINOZA
WHO IS FROM THE CERNIC INSTITUTE
AND DR. HANDEL FROM UNIVERSITY
OF NORTH CAROLINA AND TODAY'S
HER FIRST OFFICIAL DAY AT UNC
AND DR. ALFROTI FROM MONTREAL
AND DR. SAHA ON BEHALF OF OTHERS
AND THE LAST BUT NOT LEAST
DR. RESNIK FROM CHILDREN'S
HOSPITAL OF PHILADELPHIA.
WELCOME ALL OF THEM AND
MR. DAVID EAGAN WILL INTRODUCE
THE TEAM.
WE MAY NOT HAVE TIME FOR Q&A
HOWEVER, WE HAVE A NIGHT
RECEPTION AT THE HYATT HOTEL.
HOW'S EVERYBODY DOING?
I'M DAVID EAGAN A MAN WITH DOWN
SYNDROME TO ADVOCATE FOR
RESEARCH AND IT'S AN HONOR TO
INTRODUCE DR. ESPINOZA AND HIS
TEAM IN THE DATA COORDINATING
CENTER.
THE DCC IS A CRITICAL CENTER AND
IMPORTANT PIECE TO ENSURE ALL
THE RESEARCHERS COULD HAVE
MEANINGFUL PROJECTS WITH REAL
DATA.
AS MANY KNOW ME I'M AN ADVOCATE
AND SUPPORTER OF RESEARCH.
ESPECIALLY WHEN IT'S RELATED TO
DOWN SYNDROME ISSUES.
HAVE I BEEN INVOLVED IN RESEARCH
STUDIES FOR A LONG TIME AND
CONTINUE TO BE ENGAGED AS A
PARTICIPANT AND HOPEFULLY A
BENEFICIARY OF THE FINDINGS AND
RECOMMENDATIONS IN THE NEAR
FUTURE.
I WOULD LIKE TO ENCOURAGE TO YOU
PARTICIPATE AND SHARE YOUR DATA
WITH A DATA COORDINATING CENTER.
RESEARCH IN THE PAST 40 YEARS
HAVE MADE IT POSSIBLE FOR US TO
LIVE LONGER.
MANY QUESTIONS STILL HAVE NO
ANSWERS AND MORE RESEARCH AND
BREAKTHROUGHS ARE NEEDED TO
IMPROVE THE QUALITY OF OUR
LIVES.
IN THE PAST TWO YEARS, AFTER
COVID I'VE BEEN VERY SICK AND
LOST 85 POUNDS.
IT WAS A VERY SHORT TIME.
I WAS IN THE HOSPITAL THREE
TIMES.
ENDING UP IN THE INTENSIVE
CARDIAC UNIT WITH A COLLAPSED
LUNG.
I FEEL BETTER NOW AND I'M ON THE
ROAD TO RECOVERY.
I HAVE TO TELL YOU THAT MANY OF
THE HEALTH PROFESSIONALS DID NOT
KNOW WHAT WAS HAPPENING TO ME.
AND WE NEED MORE DATA TO UNVEIL
SOME OF THE UNIQUE HEALTH ISSUES
WE FACE.
WHY SHOULD I CARE IN DOWN
SYNDROME INCLUDE PROGRAM?
I STRONGLY PLAY RESEARCH CAN
PLAY A CRITICAL ROLE IN OUR WELL
BEING.
GOOD RESEARCH IS THE BEST
INVESTMENT.
MAYBE A LONG PROCESS AS OUR
PARENTS WHO ARE RESEARCHERS
EXPLAIN TO ME DISCOVERIES DO NOT
TRANSLATE IMMEDIATELY INTO
REMEDIES.
IT TAKES TIME AND A TEAM TO TAKE
SCIENCE FROM THE LAB INTO THE
MARKET AND IN THE HOMES OF THOSE
WHO NEED IT.
WHEN I TURNED 40 SIX YEARS AGO,
I WONDERED WHAT THE FUTURE WOULD
LOOK LIKE.
WHILE WE MADE SOME PROGRESS AND
ACCEPTED PEOPLE WITH
INTELLECTUAL DISABILITIES,
EFFORTS HAVE BEEN IMPROVED AND
THERE'S STILL BARRIERS TO
HEALTHY LIVING.
WE HAVE NOT YET EXPLORED HOW TO
GROW NEURONS IN THE BRAIN,
IMPROVE MEMORY, COGNITION,
LEARNING AND INCREASE OUR WELL
BEING.
WE ALL NEED TO BE ACTIVE
PARTICIPANTS IN THAT PROCESS.
RESEARCH HAS ALWAYS BEEN
IMPORTANT TO ME AND MY FAMILY.
IVE I'M INVOLVED IN THE NIH
EFFORTS AND PARTICIPATED IN THE
PROJECT.
RESEARCH IN THE HUMAN CONDITION
IS AN AMAZING SUBJECT.
IT'S A FIELD THAT IS OF HIGH
INTEREST TO ME AND ALL OF US AS
WE THRIVE FOR A BETTER QUALITY
OF LIFE.
IT MATTERS TO ALL OF US WITH OR
WITHOUT A DISABILITY.
IN MY BOOK, MORE LIKE I HAVE A
FULL CHAPTER HIGHLIGHTING HOW
RESEARCH INPART HAS SHAPED MY
LIFE.
AND HOPEFULLY IT WILL IMPROVE
ALL OF OUR LIVES AND THAT OF OUR
LOVED ONES.
IN FACT OUR QUALITY OF LIFE THAT
MANY OTHERS WITH AND WITHOUT
DOWN SYNDROME COULD BE IMPROVED
WITH FURTHER RESEARCH FROM THE
WOMB TO THE GRAVE.
OTHER RESEARCH IS NEEDED AND THE
CHROMOSOME MAY UNLOCK NOT ONLY
THOSE WITH DOWN SYNDROME BUT ALL
OF US.
I'M NOT ASKING SCIENTIST TO
CHANGE ME.
I'M COMFORTABLE WITH WHO I AM.
ANYTHING THAT CAN GIVE US AN
EDGE TO LIVE FULFILLING LIVES IS
WORTH PURSUING.
I WANT YOU TO JOIN ME AND
DR. ESPINOZA IN THESE EFFORTS.
WE'RE HOPING TO GETTING YOU
FIRED UP AND READY TO
PARTICIPATE.
REMEMBER WE THE PEOPLE WITH DOWN
SYNDROME DO MATTER AND WE NEED
YOUR PARTICIPATION.
AND THIS IS A QUAL TO ACTION.
ARE YOU READY TO ENGAGE AND
SHARE?
ARE YOU?
JUST CHECKING.
AND NOW IT'S MY PLEASURE TO
INTRODUCE DR. ESPINOZA, THE
LEADING SCIENTISTS IN OUR
COMMUNITY TO GIVE US MORE
INSIGHT INTO THE RESEARCH
EFFORTS AND KEY CONTRIBUTIONS
FROM THE NIH DATA COORDINATING
CENTER.
IN THE NAME OF ALL INDIVIDUALS
WHO SHARE WITH ME IN EXTRA
CHROMOSOMES AND ALL OF THEIR
FAMILIES.
I'D LIKE TO THANK DR. ESPINOZA
AND HIS TEAM.
PLEASE JOIN ME IN WELCOMING THE
LEADER OF THE DATA COORDINATING
CENTER AND MY FRIEND,
DR. ESPINOZA.
>> OUR FRIENDS IN THE BACK OF
THE ROOM HELP US GET THE SLIDES
GOING, I WANT TO I'M VERY HAPPY
YOU'RE BACK.
WE WERE VERY WORRIED ABOUT YOU
WHEN YOU WERE FIGHTING WITH
RECOVERY.
HE DIDN'T SAY HE GOT COVID IN
THE LINE OF DUTY HE WAS IN
CONGRESS ADVOCATING, INSPIRING
AND ADVANCING AND THAT'S HOW WE
GOT COVID AND HE WAS IN A BAD
PLACE.
BUT MOM NEVER GAVE UP.
SHE TALKED TO A LOT OF US.
SHE EXPLORED OPTIONS AND
ACCEPTED THAT STATE AND NOW
DAVID IS BACK.
MY NAME IS JUAQUIN HE ESPINOZA
I'M HAPPY TO INCLUDE THE WORK OF
THE INCLUDE COORDINATING CENTER.
OUR MISSION IS TO ACCELERATE
DISCOVERY WOULD IMPROVE AND
ENRICH THE PEOPLE OF LIVES WITH
DOWN SYNDROME THROUGH
COLLABORATION AND CONNECT TO
COMMUNITIES AND THE EXPANSION OF
A GLOBAL DOWN SYNDROME ECO
SYSTEM.
WE WILL DO THIS BY FOLLOWING THE
GUIDANCE.
WE HEARD THE CALL OF YEARS AGO
AND NIH CALLED FOR A DATA
COORDINATING CENTER THAT COULD
ACCELERATE DISCOVERY AND THE
PATHWAYS THAT ARE LEADING TO THE
CO-OCCURRING CONDITIONS BY
FACILITATING ACTION AND LOOKING
AT DATA FROM COHORTS OF
INDIVIDUALS WITH DOWN SYNDROME
AND WE'RE ORGANIZE THE WAY NIH
INSTRUCTED US TO IN THE
ADMINISTRATIVE AND OUTREACH
CORE, PROVIDING PROGRAM
MANAGEMENT, OUTREACH AND
EDUCATION AND THE HARMONIZATION
OF DATA AND CREATING THE ONLINE
WEB PORTAL.
MY COLLEAGUES LEAD THE
ADMINISTRATIVE AND OUTREACH CORE
AND THEY OVERSEE THE DATA
MANAGEMENT CORE AND ADAM,
VINCENT AND JACK REPRESENTED BY
THE CORE AND SIX P.I.s AND
DIVERSITY OF OPINIONS AND
APPROACHES.
THIS IS A CLOSE COLLABORATION
WITH NIH AND THE IT PROJECT
SCIENTIST IS INVOLVED IN EVERY
DECISION SO ARE SEVERAL OTHER
PROGRAM OFFICERS LISTED HERE.
AND THE POINT OF OUR STUDY IS
WHERE WE HAVE A SIZABLE
POPULATION WHERE WE CAN LOOK AT
THOUSAND OF MEDICAL RECORDS TO
REVEAL THEY HAVE A DIFFERENT
CLINICAL RISK PROFILE.
IT'S VERY RARE TO HEAR WHEN A
DIFFICULT IS HAVING CONSEQUENCE,
FOR EXAMPLE.
FOR EXAMPLE, THEY'RE HIGHLY
PREDISPOSED TO THE NUMBER OF
CONDITIONS SHOWN HERE AND
CANCER, ATHEROSCLEROSIS,
HYPERTENSION AND ALLERGIES AND
AUTO IMMUNITY AND ALZHEIMER'S
AND LIEUKEMIAS AND COVID-19.
TO HELP THEM LIVE LONGER WE JUST
NOT ONLY STUDY THESE BUT THE
MECHANISMS BY WHICH THE EXTRA
CHROMOSOME CAUSE THE
CO-OCCURRING CONDITIONS.
HOW ARE WE GOING IT MAKE
DISCOVERIES?
WE'RE GOING LET PEOPLE WITH DOWN
SYNDROME HELP US AND LOOK AT A
PEOPLE WITH GREAT DETAIL NOT TOO
INDIVIDUAL AND YES, SOME OF THEM
IN THE PICTURE MAY HAVE MULTIPLE
CO-OCCURRING CONDITIONS, SOME
MAY NOT AND SOME MAY PLAY
SEVERAL MUSICAL INSTRUMENTS IN
FRONT OF LARGE AUDIENCES AND
SOME MAY NOT AND THESE DIVERSITY
PRODUCE DISCOVERIES.
WE BELIEVE IN THE PERSONALIZED
MEDICINE APPROACH.
YOU ALL HAVE GREAT IDEAS WHAT IS
CAUSING THIS AND SOME THINK IT'S
GENETIC VARIANCE AFFECT THE
CHROMOSOME OR MODIFIER GENES AND
SOME MAY BELIEVE IN EPIGENETIC
MECHANISMS ACQUIRED DURING
DEVELOPMENT AND IT'S POSSIBLE
THE PHENOTYPES OF DOWN SYNDROME
ARE MATCHED BY VARIATIONS IN THE
ENDO TYPE AND WE'LL LOOK AT
RACE, ETHNICITY, LIFESTYLE AND
SOCIAL FACTORS AND WE NEED AN
EFFORT TO AID US IN TESTING
THEY'LL HYPOTHESES WITHIN OUR
LIFE TIMES.
I'M SO THRILLED TO SHARE WITH
YOU THERE ARE MORE THAN 50
INCLUDE-FUNDED COHORT STUDIES.
NEVER EVER IN THE HISTORY OF
HUMAN KIND WERE THERE SO MANY
SCIENTISTS TRYING TO HELP PEOPLE
WITH DOWN SYNDROME ACROSS
DIFFERENT INSTITUTES.
THE DIVERSITY OF APPROACHES AND
PLATFORMS, THOUSAND OF
PARTICIPANTS RECRUITED IN
RESEARCH STUDIES ACROSS THE USA.
NOW, YOU'RE ALL DOING YOUR THING
CH IS -- WHICH IS GREAT AND WEE
BETTER TOGETHER THROUGH THE
INTEGRATION.
WE PUT THE DATA TOGETHER, WE
HAVE A MORE DIVERSE COHORT AND
LARGER SAMPLE SIZE AND STRONGER
STATISTICAL POWER AND WE'LL BE
ABLE TO FILL IN GAPS THAT MAY BE
THERE.
SO WE'RE VERY HAPPY WITHIN 18
MONTHS OF STARTING OPERATIONS
AND THE SYNDROME, 2022, MARCH
21, 2022 WE LAUNCH THE DATA HUB
AND SINCE THEN WE HAVE BEEN
ADDING MORE STUDIES AND MORE
FEATURES TRYING TO MAKE IT
BETTER AND BETTER FOUR.
I WANT IT TAKE A MOMENT TO
ACKNOWLEDGE THE REMAINING
STUDIES CONTRIBUTING AND THESE
ARE THE MEMBERS OF PARTICIPANTS
AND I WOULD LIKE VERY MUCH HAVE
THE DATA SLIDE WITH MORE OF YOU.
IT'S OVERWHELMING BUT HAVING IT
LARGER IN TWO YEARS FROM NOW AND
IF YOU GO TO THE DATA HUB
THERE'S MORE THAN 9,000 DATA
SETS AND 4,000 PLUS WHOLE GENOME
SEQUENCES AND 1700
TRANSCRIPTOMES AND YOU LOOK AT
THE COGNITIVE DATA AND FITNESS
AND EXERCISE DATA AND WE'RE
MAKING SURE NO STONE IS LEFT
UNTURNED.
STUDYING THIS AND WHAT WE'RE
WITNESSING IS THE BURGEONING
DATA CONSISTENT AND FOR A LONG
TIME IT WAS ONLY.
THE ONLY RESEARCH FOR REPORTED
DATA FROM THE FAMILIES AND
SELF-ADVOCATE AND RECRUITMENT
TOOL AND DEVELOPED THE TRISOM
EXPLORER FOR THE DATA SETS AND
THE WEBSITE YOU CAN GO FIND ALL
THE INVESTIGATORS OR
PUBLICATIONS AND GRANTS TO HELP
CENTER THE NEWSROOM AND AT THE
HEART OF THE LARGE DATA SETS OR
CONTROL ACCESS ENVIRONMENT, MANY
STUDIES WHICH ARE COMPUTING AND
NOW COMING SOON AS DR. BIANCHI
MENTIONED WE'RE TRYING TO SHARE
ANIMAL MODELS.
WE'RE DOING ALL THIS BY
LISTENING TO YOU.
WE WANT TO MAKE SURE IT'S TUNE
TO THE COMMUNITY AND TO THE
CONFERENCES WHERE WE WERE LAST
YEAR.
THERE'S FOUNDATIONS AND SOME ARE
GENETIC CONFERENCE AND SOME ARE
CONFERENCES AIMED AT UNDER
REPRESENTED MINORITIES.
AND ANOTHER PART IS MAKING SURE
WE HAVE A LONG LASTING LEGACY
THAT WE GET ALL THE DATA PUT IT
SOMEWHERE SAFE AND TRAIN THE
NEXT GENERATION OF DIVERSE
SCIENTISTS AND BENEFIT PEOPLE
WITHOUT SYNDROME AND SUPPORT NIH
WE'VE BEEN ABLE TO LAUNCH THE
RESEARCH AND NOW OFFERED FOR THE
THIRD TIME THE COMING SUMMER AND
FUNDING TO OFFER IT FOR MANY
YEARS TO COME.
I WOULD LIKE TONED MY PART OF
THE PRESENTATION BY MAKE SURE
IT'S A TEAM EFFORT AND MANY
INDIVIDUALS AND MANY CONTRIBUTES
TO THE ADMINISTRATION AND
OUTREACH AND PASS IT NOW TO
ROBERT CAIRO TO TAKE US INTO THE
MORE TECHNICAL ASPECTS OF THE
DATA COMMUNITY.
>> HI, I'M EXCITED TO SPEAK WITH
YOU.
I'M ROBERT CARROLL THE NEW LEAD
OF THE DATA MANAGEMENT CORPS.
IT'S A HUGE COLLABORATION ACROSS
MANY INSTITUTIONS.
SO WE'RE ALL SUPER EXCITED TO BE
ABLE TO WORK WITH YOU AND HELP
IMPROVE THE DATA ECO SYSTEM.
THE JOURNEY OF A DATA SET IS
SOMETHING WE TALKED ABOUT WAS
ALLUDED TO AND SOMETHING
CRITICAL THEY WANTED TO FOCUS ON
WITH YOU ALL TODAY.
OUR GOAL IS TO INCLUDE
RESEARCHER NEEDS AND THE
BROADERER RESEARCH COMMUNITY.
WOE WE WANT TO HELP ALL OF YOU
IN THOSE AREAS AND WE WANT TO
GET DATA FROM YOU AND WHAT
YOU'RE DOING AND SHARING THAT IN
ANALYSIS WITH THE BROAD RESEARCH
COMMUNITY.
OUR GOAL HERE IN THE DATA
COORDINATING CENTER IS TO BUILD
THESE REUSABLE CENTERS OF
SOFTWARE AND WORK WITH ITERATIVE
PROCESSES AND ACKNOWLEDGING THE
SHARED RESPONSIBILITY BETWEEN US
AND YOU TO MAKE THE DATA USEFUL
AND AVAILABLE TO OTHERS AS WELL
AS HELPING MAKE SURE THE
TRACKING IS AVAILABLE AND IT'S
CLEAR WHAT'S GOING ON AND WHERE
WE ARE IN THE PROCESSES.
HOW MANY FEEL OBLIGATED TO SHARE
YOUR DETE WITH THE NEW DATA
SHARING MANAGEMENT POLICY?
HOW MANY FEEL EXCITED TO SHARE
YOUR DATA?
THAT'S AWESOME.
HOW MANY FEEL PREPARED TO SHARE
DATA?
NOT AS MANY.
I THINK THAT'S THE REALITY.
I'M SO GLAD THIS IS SUCH AN
ENGAGED COMMUNITY.
WE'VE GOT SOME BOXES CHECKED BUT
IT'S CRITICAL WE GET PREPARED
AND AGAIN THAT'S A SHARED
JOURNEY AND WHY WE'RE HERE AND
WHY I'M EXCITED TO WORK WITH YOU
ALL.
FAIR IS IMPORTANT AND HAS BEEN
OUT FOR A WHILE AND NOT
SOMETHING THAT HAPPENS
OVERNIGHT.
IT'S THE SHARED RESPONSIBILITY
WHERE WE CAN PROVIDE A WEBSITE
FOR PEOPLE TO FIND DATA BUT WE
NEED YOUR ENGAGEMENT TO SHARE
THE STRUCTURED INFORMATION.
WE HEARD ABOUT THE ANIMAL MODELS
AND WHAT'S IT LOOK LIKE IS THE
TYPE OF FEED AND IT'S IMPORTANT
AND THAT'S SHARED AN STRUCTURED
WAY.
WE ALL TOGETHER HAVE WORK TO DO
TO IMPROVE AND PROVIDE POWERFUL
TOOLS TO MAKE SURE DATA'S
FINDABLE.
SAME WITH PROVIDING SECURED DATA
SHARING MECHANISM.
WE CAN HANDLE THE TECHNICAL SIDE
AND NEED THE ENGAGEMENT ABOUT
THE CLEAN, CONSISTENT COMPLIANT
DATA.
THOSE ARE ALL IMPORTANT.
THAT'S HALFWAY THROUGH THE
JOURNEY AND I THINK IT'S
SOMETHING WE'RE INTERESTED IN
WORKING WITH YOU ALL TO CONTINUE
ON TO MAKE IT INTEROPERABLE AND
REUSABLE.
SOMETHING WE'VE DONE WELL IS
PROVIDE THE STANDARDIZED VIEW IN
THE DATA THROUGH THE PORTAL.
IT'S A GREAT TOOL SO CHECK IT
OUT.
IT REQUIRES A LOT OF INTENSIVE
WORK AND SOMETHING LIKE WE'LL
TALK ABOUT WHAT GOES INTO THAT
PROCESS BUT WE'RE ALSO PLANNING
TO RENOVATE THIS PROCESS A
LITTLE BIT TO MAKE IT MORE
ITERATIVE AND HOPEFULLY SPEED UP
WHAT WE'RE ABLE TO SHARE.
THAT'S THE ABRIDGED JOURNEY OF
DATA SET AND GET IT SHARED MORE
DIRECTLY INTO THE PORTAL.
I THINK THAT'S GOING TO BE
HELPFUL TO MAKING YOUR DATA MORE
AVAILABLE MORE QUICKLY.
SOME WORK BEING DONE CURRENTLY
AND WHILE WE'RE INTEGRATING THEM
THERE'S NOTHING WRONG WITH
GETTING DATA OUT MORE QUICKLY.
SOME MAY HAVE HEARD WE'RE TRYING
TO COLLECT MORE DATA ABOUT
STUDIES AND A SUSPECT AFTER THIS
MEETING WE'LL ENGAGE WITH EVEN
MORE OF YOU TO GET THAT GOOD
STRONG STRUCTURED INFORMATION
ABOUT YOUR STUDY TO START
SHARING IT AND THE WAND TO
PROVIDE THE ACCURATE INFORMATION
ABOUT THE DATA YOU'VE COLLECTED.
AGAIN, THIS PROCESS WILL BE
LOOKING DIFFERENT THAN THE PAST.
WE NEED TO MAKE SURE WE GET
CLEAN, CONSISTENT STRUCTURED
DATA FROM YOU.
THAT WILL BE A FUN AND EXCITING
PROCESS IN THE FUTURE.
THAT'S HOW WE CAN EMPOWER OTHER
RESEARCHERS TO CONNECT AND TON
DO TO THE POWERFUL WORK.
WE'RE EXCITED TO ENGAGE AND GET
THE NUMBERS UP AND GET THE WORK
OUT TO MORE RESEARCHERS TO
CONTINUE TO BUILD THE POWERFUL
ECO SYSTEM DESCRIBED.
I SEE MANY OF YOU TONIGHT.
PLEASE REACH OUT AND TALK TO ME
IT YOU'D LIKE.
WOULD LOVE TO HEAR WHAT YOU'RE
WORK ON AND HELP YOU SHARE DATA.
NOW IT'S MY TURN TO PASS THIS TO
TALK ABOUT DATA HARMONIZATION
FOR EMPOWERING ANALYTIC.
-- ANALYTICS.
>> HI, IT'S MY GREAT PLEASURE TO
BE HERE TODAY.
I'M GOING TRY TO UNPACK A LITTLE
BIT ABOUT WHAT HAPPENS UNDER THE
HOOD AT THE DCC AND HOW TO TAKE
YOUR DATA, MAKE IT MORE
HARMONIZED AND USEFUL TO MORE
KINDS OF RESEARCHERS AND MORE
KINDS OF RESEARCH AND HOPEFULLY
INSPIRED YOU TO ASK QUESTIONS
THIS EVENING AND OTHER MEMBERS
WHO WILL BE HAPPY TO ANSWER YOUR
QUESTIONS AS WELL.
SO FIRST, A LITTLE LESSON IN
DATA MODELLING.
MY FAVORITE TOPIC.
SO I JUST WANTED TO HELP
EVERYBODY UNDERSTAND.
IT DOESN'T MATTER IF YOU'RE
DOING A CLINICAL TRIAL OR HAVE
MODEL ORGANISM DATA OR MAYBE
HAVE SOME PATIENT GENERATED
DATA.
ALL THESE DIFFERENT DATA SOURCES
FUNDAMENTALLY HAVE CHARACTER
EFFORTICS WE MIGHT BE ABLE TO
MODEL IN A CONSISTENT WAY TO
HELP US ANALYZE THEM ESPECIALLY
WITHIN THAT KIND OF MODEL BUT
ALSO IN PARTICULAR ACROSS
STUDIES.
WE HAVE INFORMATION WHERE
INFORMATION IS MODEL DIFFERENTLY
IN DIFFERENT COHORTS.
EVERY ONE JUAQUIN PRESENTED HAS
A DIFFERENT MODEL AND OUR JOB IS
TO FIGURE OUT HOW TO BRING THEM
TOGETHER.
LIKE IF A SAMPLE'S RELATED TO A
DIAGNOSIS OR CASE INFORMATION
FOR AN INDIVIDUAL RELATED TO
THAT DIAGNOSIS.
THEY'RE DIFFERENT IN DIFFERENT
DATA DICTIONARIES OR COHORTS.
IT'S DIFFERENT THAN
UNDERSTANDING HOW THE DIFFERENT
COHORTS OR MODEL ORGANISM
STUDIES MIGHT MODEL DIFFERENT
ELEMENTS OF THOSE STUDIES.
FOR EXAMPLE, FOR A COHORT YOU
MIGHT REPORT RACE WITH THE FOUR
CATEGORIES AND OTHERS MAY HAVE
MANY MORE.
IF WE WANT TO CREATE AN
INTEGRATIVE DATA SET WE HAVE TO
DECIDE HOW TO MAP NOT REPORTED
TO OTHER OR UNKNOWN.
THOSE ARE NOT THE SAME THING
THEY WERE COLLECTED IN DIFFERENT
WAYS.
WHEN YOU'RE ANALYZING THE DATA
DOWN STREAM YOU WANT TO KNOW HOW
IS THAT ALL THAT COLLECTED IN
ORDER TO NOT GET THE WRONG
RESULT.
IT'S A TEDIOUS PROFESSION.
-- PROCESS.
WE'VE BEEN DEVELOPING A DATA
MODEL FOR THE INCLUDE PROJECT
BASED ON A MODELLING LANGUAGE
CALLED LINKED ML.
IT'S LED BY DR. CAN TORRES WHO
IS ALSO HERE AND WILL BE HAPPY
TO ANSWER QUESTIONS AND PURETT
LOW AND SHE'S DONE A LOT OF THE
WORK AND CAN ANSWER QUESTIONS
YOU HAVE.
I JUST WANTED TO MENTION, THIS
MODELLING LANGUAGE ALLOWS US TO
ORGANIZE THE KNOWLEDGE ABOUT
PARTICIPANTS, CO-OCCURRING
CONDITIONS AND DATA SETS
ASSOCIATED WITH EACH STUDY.
SOUNDS SIM FASIMPLE, RIGHT?
IT'S NOT AN EXAMPLE FROM THE HTP
DATA SET IN COHORT A AND WE HAVE
A DIFFERENT ONE IN COHORT B YOU
CAN SEE WHERE WE'RE LOOKING AT
THE RACE CATEGORIES ARE
DIFFERENT ACROSS THE DIFFERENT
COHORTS.
I THINK I HAVE A POINTER.
WE HAVE RACE CATEGORIES ALL
REPRESENTED DIFFERENTLY AND HERE
WE LOOK AT THE DEFECT TO WHICH
APPLY TO A SET OF STRINGS HERE
THAT HAVE RELATED TERM SHOWN
HERE INTO ONE SET OF HARMONIZED
VALUES AND THEN GO INTO THE
PORTAL AND SEE HOW IT LOOK AT
THE OTHER END.
AND THIS TRANSFORMED DATA THEN
BASICALLY THOSE COHORTS THAT
HARMONIZATION PROCESS RESULTS IN
THIS CASE DISEASE ENTITIES OR
CO-OCCURRING CONDITIONS,
PHENOTYPIC INFORMATION, RACE
INFORMATION AND OTHER VARIABLE
HAVE BEEN HARMONIZED AND YOU CAN
NAVIGATE THEM WITHIN THE PORTAL.
OUR GOAL IS TO DO THIS FOR MANY
MORE VARIABLES AND MAKE THEM
AVAILABLE WITH THE MULTI-OMICS
DATA FOR ANALYTICS.
AND THIS IS A HOW-TO GUIDE AND
THEY WORK THEY'RE HIERARCHICAL
IN NATURE AND CLASSIFIED.
YOU CAN SEE THE NATIONAL OF
PATIENTS THAT HAVE ABNORMAL
HEART MORPHOLOGY BUT ANY
INDIVIDUALS WITH DOWN SYNDROME
WHO ALSO HAVE SEPTUM MORPHOLOGY
WOULD BE COUNTED AS PART OF THE
ABNORMAL MATTER MORE --
MORPHOLOGY AND THIS IS WHY IT'S
IMPORTANT TO HAVE A DATA MODEL
AND THIS MORNING'S SESSION WAS
ILLUMINATING IN THE GREAT NEED
FOR STANDARDIZING RESEARCH DATA
AND WE HAVE CLINICAL DATA MODEL
FOR INCLUDE AND FROM THE MONARCH
INITIATIVE HAVE A BASIC MODEL
FOR THE STRATEGY ON THE RIGHT
BETWEEN PHENOTYPES AND THIS IS
AN EXAMPLE THAT COMES FROM A LAB
AN THEY'RE HERE TODAY SO YOU CAN
ASK ABOUT THE WORK BUT USING THE
BASIC RESEARCH DATA MODEL THAT'S
BEEN POPULATES WITH BASIC
RESEARCH DATA AND COMPARE THAT
TO INFORMATION THAT WE HAVE
COMING PERFECT THE COHORTS AND
REPRESENTATIVE USING INCLUDE
DATA MODEL TO LOOK AT
CILIOPATHIES AND THIS IS A
PRELIMINARY EXAMPLE OF TRYING TO
EXERCISE HOW WE CAN USE TO THE
DATA MODELS TO ALIGN THE BASIC
RESEARCH DATA WITH THE CLINICAL
DATA AND WITH THAT I'LL HAND IT
OFF.
>> THANK YOU.
I'M AND I'M WITH THE CHILDREN'S
HOSPITAL, PHILADELPHIA.
THE DATA PORTAL IS MEANT TO BE A
COMPREHENSIVE DISCOVERY
PLATFORM.
THE FIRST MISSION IS TO MAKE ALL
THE DATA ACCESSIBLE.
THERE'S MODALITIES AND SOURCES
OF DATA THAT WE RECEIVE FROM THE
DOWN SYNDROME STUDY PARTICIPANT
IN THE PROGRAM INTO A SINGLE
UNIFIED DAT PLATFORM.
I HAVE ONLY MINUTES TO PARENT
THE SOFTWARE.
I'LL INTRODUCE FOUR DATA
DISCOVERY TOOLS AND THE STUDY
REPOSITORY AND THE BIO EXPLORER.
THE CORD BUILDER IS THE TOO MANY
THAT LEVERAGES OUR EFFORTS IN
DATA ORGANIZATION.
IN THIS SEARCHING OF DATA ACROSS
MULTIPLE STUDIES AND BUILDING OF
PARTS FROM MULTIPLE STUDIES.
AND THERE'S A COHORTS YOU CAN
SEARCH.
ON THE LEFT YOU SEARCH CRITERIA
RELATES TO BIO PARTICIPANT AND
DATA FILES AND WITH THESE YOU
CAN FORMULATE COMPLEX QUERIES.
FOR EXAMPLE, I HAVE A QUERY THAT
CAN BE READ AS FINDING ALL THE
TRISOMIC PARTS ANDAGE WE HAVE
GENE EXPRESSION DATA.
WE HAVE DIFFERENT QUERY.
THEY CAN KIND THEM AND SAVE THEM
NAY WANT TO CHECK IF THERE'S NEW
IN THE COHORT.
THERE'S THE RESULT IS THE
SUMMARY VIEW THE GRID
CUSTOMIZABLE WITH INTERACTIVE
CHARGE IMMIGRATION.
-- AGGREGATION WE HAVE BUILT
THIS ONTOLOGY BROWSERS SO THE
ENTIRETY OF TERMS FOR THE HPU
AND ONTOLOGY AND TOGETHER WITH
ON THE RIGHT SIDE COUNTS FOR
EACH AND SUB NOTE.
AND THE SEARCH ENGINE WILL
RETURN PARTS WITH THIS EXACTER
BUT ALSO THE PARTS WITH THE TAG
UNDER THE SUB NOTE AND TERM
SELECTED.
THIS IS OUR WAY TO DIFFERENT
WITH A DEAL LEVEL OF PRECISION
ACROSS COHORT.
THERE'S THE PARTS PANEL VIEW AND
THE TABLE THE PARTICIPANTS THAT
WILL MEET THE CRITERIA.
SO EACH REPRESENT A PARTICIPANT
WITH THE CLINICAL DATA OR THE
YOU HAVE THE BIO SPECIMEN AND WE
HAVE COUNTS LINKED TO EACH
PARTICIPANT.
IT GIVES A SENSE OF AVAILABLE
RESOURCES FOR INVESTIGATION.
THE THIRD IS A TABLE OF FIVES
AND SO NICE THING WITH THE VIEW
IT'S FULLY INTEGRATED TO THE
PLATFORM.
IT MEANS FOR EXAMPLE FOR
INSTANCE IN THIS EXAMPLE THE
LIST OF FIVES WOULD BE THE GENE
EXPRESSION IDENTIFIED THAT WE
HAVE FOUND.
AND THEY CAN TRANSFER THEM TO
THE PRIVATE WORK SPACE ON THE
CLOUD.
WE'LL TALK MORE ABOUT THE
PLATFORM.
INTEREST TRANSFERRING THIS?
IT'S FOR DOING FURTHER
STATISTICAL OR BIO INFORMATIC
ANALYSIS.
T
IT ENABLE THE SEARCHING OF BIO
SPECIMEN AND PERMISSION OF
REQUESTS TO THE BIO BANK.
IT'S A TABLE OF BIO SPECIMEN
THAT MEET THE SEARCH CRITERIA
AND THE RESEARCHER COULD SELECT
THEM AND HAVE A REPORT SUBMITTED
TO EACH BIO BANK IN THE SPLENGS
CURRENTLY, INCLUDE THE IT DATA
WE HAVE 25,000 MORE THAN 25,000
SAMPLES FOR WHICH WE HAVE THE
TYPE AND LABORATORY PROCESSOR
AND LINEAGE FROM THE FIRST
COLLECTION THERE THE PARTICIPANT
TO THE GENE EDITING CODE SO A
LOT OF INFORMATION THAT CAN BE
MADE AVAILABLE TO THE PORTAL.
ANOTHER TOOL IS THE STUDY
REPOSITORY.
IT'S A SEARCHABLE CATALOG OF
STUDIES AND DATA SETS.
SO THESE STUDIES AND DATA SETS
CAN BE SEARCHED USING DIFFERENT
CRITERIA AND THE RESEARCH AND
DATA SOURCE AND SO ON.
THOUGH IT LOOKS SIMPLE IT PLAYS
A MAJOR ROLE IN THE COMING
YEARS.
IT INCLUDES NOT ONLY HARMONIZED
DATA BUT NUMEROUS STUDIES AND
THEIR DATA SET.
IT'S A WAY FOR STUDIES THAT ARE
NOT HARMONIZED YET SO IT'S A NEW
TYPE OF DATA THAT WILL MAKE IT
DISCOVERABLE AND THIS IS THERE'S
A STUDY PAGE WITH A LOT OF
INFORMATION WE LAUNCHED LAST
WEEK.
A LOT OF INFORMATION CAN BE
FOUND ON THE STUDY PAGE AND NE
PRINCIPLE INVESTIGATORS AND
SUMMARIES AND DATA ACCESS
POLICIES AND ALSO SOME FUTURE
DATA SETS THAT ARE MAYBE
REFERRED TO BY PUBLICATION AND
OTHER INFORMATION.
ALL THIS IN A SINGLE PAGE VERY
CONVENIENT AND WILL HELP RELEASE
DATA FASTER.
THE LAST TWO I'D LIKE TO TALK
ABOUT IS THE EXPLORER.
SO THIS TOOL ENABLED THE SEARCH
ACROSS MILLIONS OF VARIANTS WITH
NO CURRENT CONDITIONS.
SO WHAT WE DO IS THE FOLLOWING.
AND THERE'S VARIANTS IN VCF FIVE
A TECHNICAL TERM THEY'LL
VARIANTS ARE PRODUCED IN FILES
AND EX TRACT THEM AND ANNOTATE
THEM IN A DATABASE AND SEARCH
LIKE THE CORD BUILDER WITH
FREQUENCIES AND YOU GET A LIST
OF VARIANTS WITH THE MOST
CONSEQUENCE AND THEN YOU HAVE
ALSO THE FREQUENCY WITHIN THE
INCLUDE COHORT WITHIN EACH STUDY
AND WHEN THE VARIANTS PRESENT IN
MORE THAN 10 YOU HAVE A LINK AND
YOU CAN GET THE LIST FROM THE
CORD BUILDER OF THE PARTICIPANT
THAT CARRY THESE VARIANT.
CURRENTLY WE HAVE 74 MILLION
VARIANT INTERESTS TWO STUDIES IN
OUR DATABASE.
SO EACH VARIANT WE HAVE A
VARIANT PAGE AND IT'S A NEW ONE
LAUNCHED LAST WEEK CONTAINING
ALL THE INFORMATION YOU CAN GET
FROM A VARIANT.
ALL THE FREQUENCIES AND ALL THE
ANNOTATION AND THE GENE TO
PHENOTYPE CESSATION AND WITH ODD
AND OTHER INFORMATION.
SO THE FUTURE WORK AND SO I
THINK WE'LL KEEP OVER THE NEXT
YEAR WE'LL KEEP IMPROVING WHAT
WE'LL SHOW YOU.
IT MEANS THE DATA DISCOVERY SIDE
AND BUT WE WANT TO GO START AT
THE NEXT PHASE TO INTRODUCE MORE
DATA.
SO WE'LL HAVE DATA TOOLS LIKE
GENE EXPRESSION AND COMPARISON
AND WANT ALSO TO DEVELOP THIS
LONGITUDINAL VIEW OF THE
CLINICAL DATA FOR THE
PARTICIPANT.
THIS IS WHAT WE'RE GOING TO WORK
ON OVER THE NEXT YEARS AND ALL
THIS IS INTEGRATED IN A
DASHBOARD I DIDN'T HAVE THE TIME
TO PRESENT BUT WOULD BE A VERY
EASY TO ACCESS.
>> I KNOW THERE'S BEEN COMPLEX
STEPS THAT HAVE BEEN DESCRIBED.
WE TRIED TO CAPTURE THIS IN AS
FEW NUMBER OF SLIDES.
REACH OUT TO US IF YOU WE HAVE
GLOSSED OVER AND I WILL GLOSS
OVER TEAMS BUT TO SHOW YOU THE
JOURNEY THE TEAM ROBERT STARTED
WITH.
IT'S NOT THE LAST STEP AND IT'S
A PLACE WE'D LIKE TO YOU DO
CLOUD ANALYSIS AND BRING DATA
SETS THAT EXIST AND MOVE IT OUT
AND PROVIDE YOUR LAPTOP AND
WHERE YOU NEED TO TAKE THE DATA.
THE IDEA IS AND WHEN YOU THINK
OF THE CLOUD YOU THINK OF A WAY
TO INTEGRATE RESOURCES CHEAPLY,
FASTER IN A WAY THAT COULD NOT
BE DONE BEFORE.
IF THAT DOESN'T MAKE SENSE
PLEASE TALK TO ME.
AND THIS IS AGNOSTIC IF YOU
THINK BIT.
WE WOULD LIKE USERS AND WE WANT
TO YOU THINK ABOUT THE CLOUD AS
AN ASSET.
YOU CAN COLLABORATE AND REUSE
AND MAKE YOUR DATA USABLE,
REPRODUCIBLE AND EXTENDIBLE AND
SCALABLE AT COMPUTE.
THESE ARE NOT BUZZ WORDS BUT TRY
TO TOUCH ON THIS IN DIFFERENT
USER PERSONA.
THE VALUE THAT COMES IN IS ALL
THE OTHER CONSORTIUMS USING THE
PLATFORM AND YOU'LL LIKELY GET
ACCESS TO THE DATA SETS.
WHY'S THAT IMPORTANT?
SO FOR EXAMPLE, CONSIDER
CAVATICA WE'RE HERE FOR THE
INCLUDE CONSORTIUM BUT IT'S
CONNECTED TO OTHER DATA SETS
LIKE PUB MED AND OTHER DATA SETS
AND EVERYTHING LIKE TCGA AND YOU
CAN BE PROVIDED WITHOUT COPYING
IT.
YOU CAN START USING IT ON
CAVATICA WITHOUT PAYING ANYTHING
FOR STORAGE WHICH MEANS A LOT AS
YOU SCALE UP YOUR COMPUTE.
AND THERE'S AUTHENTICATION
REQUIRED FOR CERTAIN DATA SETS.
SO THESE ARE DIFFERENT PERSONAS.
SO WHY ARE THE CLOUD COMPUTE
PLATFORM USEFUL?
THINK OF THIS AS A FLOW.
ADMINISTRATORS WHO ARE PROVIDING
FUNDING WOULD LIKE TO KNOW HOW
IT'S BEING USED BY DIFFERENT
RESEARCHERS.
MATHEMATICIANS CAN PRODUCE THOSE
AND GIVE IT TO THE BENCH
SCIENTIST TO PLUG IT IN AND TAKE
REPORTS FROM IT AND GIVE THAT TO
A CLINICIAN AND THEN ONCE
EVERYBODY'S HAPPY WITH THE
PROTOTYPE BUILT IT CAN BE
PRODUCTIONIZED AND MADE SCALABLE
AND NOW THE BUZZ WORDS COME BACK
AND MADE MORE SCALABLE BY
DEVELOPERS.
YOU CAN LOOK AT DIFFERENT
PERSONAS WHO IN OTHER WAYS HAVE
TO GO THROUGH DIFFERENT
PROCESSES AND WORK TOGETHER IN
THE SAME ECO SYSTEM.
AND YOU CAN HAVE MULTIPLE USERS
I WON'T GO INTO DETAIL BUT YOU
THINK OF IT AS A CLOUD WORK
SPACE WHERE YOU CAN PUT YOUR
DATA ACCESS AND OTHER TEAM'S
DATA AND SHARE YOUR DATA WITH
SELECTIVE COLLABORATORS,
STUDENTS, YOU DECIDE WHO.
SO YOU CAN USE DIFFERENT WORK
FLOW LANGUAGES WHICH ARE
LANGUAGES IN WHICH YOU WRITE
PIPELINES AND THE FLOW AND USERS
OF BOTH IN THE ROOM.
R STUDIO AND SUPER TER ARE TWO
OF THE MOST COMMONLY INTERACTIVE
PROGRAMMING TOOLS WHICH YOU CAN
USE AND THEN OF COURSE ONCE
YOU'RE HAPPY WITH THAT TOOLING
YOU CAN CREATE WEB APPLICATIONS.
I WANT TO TAKE A SECOND TO TALK
ABOUT JUPYTER AND R STUDIO AND
YOU CAN MOVE IT TO JUPYTER LAB
AND R STUDIO IN THE CLOUD THEY
CAN USE IT WITHOUT COPYING IT.
THAT MAY BE USEFUL.
THIS IS A QUICK SNAPSHOT.
START FROM THE PORTAL YOU CLICK
AND THE BUTTON.
THIS MEANS THE FILES ARE NOT
COPIED TO CAVATICA ONLY THE
POINTERS.
YOU'RE NOT PAYING ANYTHING FOR
STORAGE.
YOU CAN PLUG IN DATA AND SOME
TODAY IS AUTOMATICALLY
POPULATED.
YOU CAN ANALYZE IT OR CONNECT TO
OUR METADATA SERVER CALLED THE
FIRE SERVER.
YOU DON'T HAVE TO WORRY ABOUT
DATA AT THIS POINT.
YOU CAN BRING ALL OF IT TOGETHER
IN A WORK FLOW AND GET YOUR
SCIENTIFIC ANALYSIS DONE.
THIS IS THE JOURNEY FROM
SEARCHING FOR THE DATA AND THE
NEED OF CAVATICA AND DOING IT
ALL IN THE CLOUD USING CLOUD
CREDIT.
SO, TODAY YOU CAN GO IN.
ANYBODY CAN CREATE A LOG IN IN
THE E-MAIL AND YOU CAN GET
HUNDRED DOLLARS OF CLOUD CREDIT
TO PAY IN THE PLATFORM.
WE HAVE A SIMPLE CLOUD CREDIT
APPLICATION PROGRAM WHICH IS AN
E-MAIL TO A FRIENDLY GROUP OF
PEOPLE TO GET ANALYSIS AND WE
CAN KEEP ON WORKING WOULD
SCALING THAT UP.
WE HAVE MEANS TO HELP YOU BUILD
WORK FLOWS AND UNDERSTAND WHAT
ALL THE TECHNOLOGY MEANS AND
THERE'S A QR CODE AND I POSTER
UP THERE.
IT TALKS ABOUT IT MORE AND HAVE
QUESTIONS TALK KNOW AND ASK ME
WHY YOU SHOULD THINK ABOUT CLOUD
COMPUTE.
WE'D LIKE TO HELP YOU MAKE THE
TRANSITION IF YOU THINK IT'S GAI
IDEA AND NEXT DR. RESNIK WILL
COME IN AND CLOSE THE SESSION.
MY JOB IS TO BE THE CLOSER AND
EXPLAIN WHAT EVERYBODY SAID TO
YOU.
I WON'T DO THAT.
WHAT YOU SAW WAS AN AMAZING TEAM
TO PROVIDE DATA AND IN A SECURE
AND GOVERNANCE ALIGNED FRAMEWORK
AND CLOLLABORATE DISCOVERY AND
IMPACT PATIENTS.
ONE WAY TO SIMPLIFY IT IS TO
REDUCE BARRIERS FOR DATA TO COME
OUT.
THAT'S WHAT WE SPENT THE
MAJORITY OF THE LAST SEVERAL
YEARS DOING AND IT'S A REQUIRED
FOUNDATIONAL INFRASTRUCTURE TO
DO THE KIND OF WORK PART OF
INCLUDE.
FOR ME THOUGH THE PART THAT'S
EXCITING ABOUT INCLUDE IS THAT
YOU'RE DOING SOMETHING THAT VERY
FEW, TO MY KNOWLEDGE, MAYBE NO
OTHER COORDINATING EFFORTS
AROUND A PARTICULAR CONDITION OR
DISEASE CONTEXT HAS EVER DONE.
EVEN TODAY YOU BRING TOGETHER
CLINICAL TRIALISTS, BASIC
SCIENTISTS, COHORT CREATION
EFFORTS IN WAYS THAT TRY TO
COMPLETE THIS ARC FROM
INDIVIDUAL STUDIES, INDIVIDUAL
PATIENTS AND PARTICIPANTS AND
BEGINS ALL THE WAY AT THE LEFT
AND THROUGH DEEP PHENOTYPING OR
CHARACTERIZATION DRIVE THE
FRAMEWORK INTO DATA THAT BECOMES
EMPOWERED AS INFORMATION AND WE
CAN DRIVE KNOWLEDGE CREATION AND
IMPACT.
THAT IS EXTREMELY HART TO DO IT
AT SCALE AND FAST.
UNIVERSALLY WHETHER YOU'RE A OR
PATIENT IN A HOSPITAL WITH DATE
OF DAVID, YOU'RE AT THE ANALOG
INDIVIDUAL LAYER AND USUALLY
THEY'RE THE MOST UNEM EMPOWERED
CONTEXT AND OUR JOB THROUGH THE
INFRASTRUCTURE IS TO DRIVE A
DIGITAL NON-LOCAL
COMMUNITY-BASED RESOURCE IN WAYS
THAT HARNESSES NEW TECHNOLOGIES
AND TOOLS IN WAYS YOU HAVEN'T
DONE BEFORE.
ULTIMATELY, THE WAY WE KNOW IT
SUCCEEDS IS IF THE IMPACT OF THE
INFRASTRUCTURE COMES BACK DOWN
TO THE INDIVIDUAL.
THAT'S SOMETHING NOT FORGET.
OUR GOAL IS TO TRANSLATE THE
INFRASTRUCTURE TO THE NEXT
PARTICIPANTS AND THEIR SPECIFIC
JOURNEY.
YOU FIND THE TRILOGY A FRAMEWORK
APPEARING.
WE ALL WHETHER YOU THINK MODEL
SYSTEMS OR CLINICAL TRIALS, OUR
FOCUS ON DEEPLY CHARACTERIZING
PARTICIPANTS, PATIENTS OR
SAMPLES, INTEGRATING THAT WITH A
SHARED FRAMEWORK OF MECHANISMS
OR OUTCOMES AS CONNECTED TO
TREATMENTS, INTERVENTION AND
RESPONSES.
THE REASON WE'RE DOING THAT IS
BECAUSE THE NUMBER OF SAESZ WE
HAVE CONTINUE TO GROW BUT THE
TECHNOLOGIES THAT CAN EMPOWER
HAVE ALSO GROWN AND THAT'S WHAT
YOU SEE THE TEAM HERE PLAYING
TOGETHER.
SO TO GET TO THAT SPACE OF
ACTUALLY BEING ABLE TO ASK THE
FOLLOWING QUESTION TO MY
KNOWLEDGE NOT EVERYBODY, ANY
HOSPITAL AND HOPEFULLY SOMEBODY
HERE CAN BE COUNTER FACTUAL CAN
ANSWER.
IF YOU HAVE A 46-YEAR-OLD
PARTICIPANT WITH DOWN SYNDROME
COMES TO YOUR HOSPITAL WITH A
COLLAPSED LUNG, WHO ARE THE
OTHER PARTICIPANTS OR PATIENTS
THAT HAVE BEEN LIKE THAT WITH
THE SAME CONDITION AND SAME
RESEARCH DATA OR CLINICAL DATA?
NOBODY CAN ANSWER THAT QUESTION
IN REAL TIME EITHER AS A
RESEARCHER OR AS A CLINICIAN.
57D CHALLENGE THE MODEL.
IN MANY WAYS AND THE INCLUDE
PROGRAM IS A TESTAMENT FOR THAT
PRECISION FRAMEWORK WRIT LARGE.
TO MY KNOWLEDGE NO ONE IS DOING
THE FRAMEWORK OF CO-CREATION
CLINICAL TRIALS, BASIC RESEARCH
AND UPCOMING COHORT PERSPECTIVE
STUDIES IN THIS COORDINATED
FRAMEWORK.
SO THIS IS A CHALLENGE.
YOU AND YOUR COMMUNITY ARE
SETTING THE STAGE WRIT LARGE CHA
WHAT IS POSSIBLE AROUND DATA
INTENSIVE RESEARCH IN WAYS THAT
COULD BE COORDINATED AND AS A
TEAM HIGHLIGHTED MULTIPLE TIMES
IT'S A RICH AREA OF
EXPERIMENTATION AND I'LL END
WITH THAT TRANSPARENCY BUT STILL
ONGOING EXPERIMENT AND THERE'S
NO PRECEDENT FOR DOING THAT.
WITH A LITTLE NEED YOUR FEEDBACK
AND CRITIQUE AND INPUT AND THE
ONLY WAY TO SUCCESS AND HAVE THE
POTENTIAL TO CHANGE OUR RESEARCH
WRIT LARGE AND BEING CONDUCTED
AND ONLY COMMUNITY-BASED
FRAMEWORKS CAN SUCCEED IN THAT
VISION AND WE HOPE INCLUDE CAN
DO THAT.
THANK YOU FOR YOUR ENGAGEMENT.
WE'LL BE AVAILABLE FOR
CONNECTING AND AGAIN CHALLENGE
US, INFORM US, ASK US QUESTIONS.
THIS IS GOING TO BE A SHARED
EXPERIMENT AS WE CONTINUE IN THE
TALK.
THANKS AGAIN.
>> THANK YOU TO THE WHOLE TEAM.
NOW WE HAVE ABOUT 15 MINUTES FOR
QUESTIONS.
>> I THINK THIS IS A FANTASTIC
TOOL AND OPPORTUNITY AND I WAS
THINKING ABOUT THE CONVERSATION
WE WERE HAVING IN THE BREAKOUT
GROUP ABOUT THE ACCESS OR
ACCESSIBILITY OF A.I. OF DATA
AND CURIOUS HOW YOU THINK ABOUT
INCORPORATING THOSE TECHNOLOGIES
INTO DIVING INTO THE DATA MORE
OR LESS BIAS THAN INDIVIDUAL
INVESTIGATORS MIGHT BE.
>> SO, YOUR POINT IS WELL TAKEN
AND WE'RE LEVERAGING NEW
TECHNOLOGIES WHETHER
INFRASTRUCTURE OR COMPUTATION.
A.I.'S A TRANSFORMATIVE
TECHNOLOGY THAT IS POISED TO
DISRUPT WHAT CAN BE DONE BOTH AT
THE INTAKE SIDE, HOW YOU GET
PROVISION AND ANALYZE AND
HARMONIZE AND THE ANALYTIC SIDE
AND AT LOWERING THE BARRIER FOR
PEOPLE WHO INTERACT WITH DATA
AND QUERY DATA.
SO WE ACTUALLY THINK OF THE
THREE LAYERS, POWER DATA, INGEST
AND CAPACITY TO BE INTEGRATED
AND HOW DO WE POWER FINDABILITY
AND CAN MERE MORTALS INTERACT
WITH DATA AND ASK QUESTIONS AND
CAN A.I. DRIVE NEW KNOWLEDGE IN
WAYS THAT'S DIFFICULT FOR HUMANS
AND IMAGINE MACHINE LEARNING
THAT DO FEATURE DETECTION AND
IMAGING AS A FRAMEWORK WHICH IS
A GREAT EXPERIMENT IN THE
CONTEMPT OF A.I.
>> HOW DO WE TAKE WHAT I CALL
GOOD OLD FASHIONED A.I. THE
ONTOLOGICAL CLASSIFICATIONS
WE'VE BEEN ABLE TO SHOW YOU AND
HOW WE'VE BEEN ABLE TO DIAGNOSIS
RARE DISEASES AND COMBINE THEM
WITH LARGER LANGUAGE MODELS AND
EVERYBODY'S WHETHER IT'S THE
BASTE RESEARCH DATA WE WERE
HEARING BEFORE AND THE PLEA,
HELP US MAKE OUR DATA MORE
FINDABLE AND INTEROPERABLE AND
HOW DO WE LOOK AT MORE THINGS OR
RELEVANT THINGS?
THE COMBINATION OF THE TWO
HOWEVER, IS INCREDIBLY POWERFUL.
PROBLEM WITH LARGE LANGUAGE
MODELS IT OUT OF THE BOX
PACKAGES IS BASED ON WHAT'S ON
THE WEB.
SO IT'S NOT LEARNING FROM OUR
OWN MOST APPRECIATION DATA BUT
AND OUR OWN STANDARDS IN WAYS WE
MODEL DATA AND THESE INCREDIBLE
TOOLS TOGETHER CAN MAKE THE
PROCESS OF HARMONIZING DATA
WHETHER IT'S A PATIENT DYING OF
A COLLAPSED LUNG OR NOT DYING OF
A COLLAPSED LUNG AS THE CASE MAY
BE, FORTUNATELY, WE'RE ABLE TO
USE THE COMBINATION TO SAY
HERE'S HOW WE REVEAL CANDIDATE
HYPOTHESES IN A LESS BIASSED
WAY.
IT'S A HUGE OPPORTUNITY AND
WE'RE COMBINING ALL THESE
TOGETHER.
>> A.I.'S NOT MAGIC AND THE KEY
PART IS FOR DATA TO BECOME A.I.
READY AS A FRAMEWORK.
SO WE CAN ASK THE QUESTION, HOW
MANY OTHER 46-YEAR-OLDS WITH
THIS PARTICULAR FEATURE SET HAVE
A COLLAPSED LIMB AND YOU DON'T
HAVE TO WRITE A SEQUEL CODE BUT
JUST ASK IT AND THAT'S WAYS TO
DO IT IN WAYS THAT ARE
TRANSFORMATIVE.
>> NYU SCHOOL OF MEDICINE.
I THINK THIS AS THE FIRST
EXAMPLE A HEALTH CARE DATA
ACROSS THE COUNTRY.
IS THERE A PLAN TO WORK WITH THE
U.K. CAN BIO BANK TO GET IT HERE
BECAUSE AT INDIVIDUAL LABS WE
ONLY DOWNLOAD SMALL PARTS AND
THIS COULD BE AN EFFORT WHERE
NIH CAN DOWNLOAD IT AND INSTEAD
OF PIECE MEALING IT AND TRYING
TO PUT IT TOGETHER.
>> I CAN APPROXIMATE AN ANSWER.
THE PRIMARY MANDATE IS FOR
INCLUDE FUNDED DATA.
HAVE A MANDATE TO COPY AND
PASTE OTHER COOL DATA SETS?
NO, BUT WE LOOK TO MAKE SURE
WE'RE INTEROPERABLE.
A
AND MAKING SURE THEY'RE
INTEROPERABLE WITH OTHER SETS.
>> THE SEAM IS VESTED IN THIS AN
MOST ARE MEMBERS OF G4, GH THE
COMMUNITY FOR DEVELOPING THE
STANDARDS AND SUPPORT DIFFERENT
DATA SETS AS MENTIONED FOR
CAVATICA AND ACROSS THE ATLANTIC
AND FURTHER BEYOND.
THERE'S POTENTIAL NEW BARRIERS
AND WHERE THEY CAN DRIVE CHANGE
IN THE LANDSCAPE.
>> THANK YOU.
I WANT TO ADD ONE THING.
WHILE WE'RE WAITING FOR THE
INTEROPERABILITY EFFORT YOU CAN
UPLOAD TO CAVATICA TO CO-ANALYZE
WITH INCLUDE DATA BUT NOT HUGE.
>> THE REAL SUCCESS FOR US IS
BEING YOU AS A COMMUNITY START
USING THE PLATFORM TO EMPOWER
YOUR DATA NOT JUST THE FIRST
DEPOSITION OF DATA BUT HAS VALUE
TO YOUR IMMEDIATE CONTEXT OF
ANALYSIS AND THAT'S WHAT WE'D
LOVE TO PARTNER WITH YOU ON.
>> THANK YOU FOR THE WORK YOU'VE
BEEN DOING FOR THE FIVE YEARS.
I DON'T ENVY ANY OF IT IN TRYING
TO HARMONIZE THE DATA SETS WE'RE
CONTRIBUTED OR GOING TO AND ARE
THERE STEPS FOR WHAT YOU'D USE
IN THE FUTURE EVEN FOR THE
VALUES FOR THE VARIABLE ARE THE
PLANS TO INCLUDE THE RACE
VARIABLES YOU SHOULD USE SO WHEN
WE'RE UPLOADING IT THERE'S LESS
EFFORTS AND STANDARDIZING THINGS
SO THERE'S LESS HARMONIZATION AT
THE END?
>> THANK YOU FOR THE QUESTION.
THE INCLUDE WORKING GROUPS
STANDARDIZATION IN 2019 AND 2020
HAVE A CORSET OF DATA ELEMENTS
WHICH WE PAID ATTENTION TO AND
NOW CALLED THE ELEMENTS OF
INTEREST IF ANYBODY'S DESIGNING
WANTS TO KNOW THE COMMON DATA
ELEMENTS ARE EASY TO SHARE.
HOWEVER, WE'RE NOT PRESCRIPTIVE.
WARE HERE TO TAKE THE DATA AND
WE HAVE A GREAT HUNT FOR MANY
SITES TO COLLECT DATA AND USING
THE STANDARD DICTIONARIES.
PERHAPS IT WILL GIVE ENOUGH
CRITICAL MASS TO BE MORE
PRESCRIPTIVE LIKE YOU WANT MONEY
THROUGH A MINI COHORT STUDY.
MAKE SURE YOU'RE COLLECTING THE
DATA THE SAME WAY AS THE
PROGRAM.
I THINK WE'RE MOVING FROM
FLEXIBLE AND LOOSE AND MOVING
TOWARDS THE RIGHT OF THAT
SPECTRUM SLOWLY BUT SURELY.
>> I'LL ADD THAT WE'RE WORK HARD
TO BUILD OUT THE BEST PRACTICE
MODEL WE'LL USE INTERNALLY FOR
THE INCLUDE DATA AND TALK ABOUT
HARMONIZATION.
WE CAN MAKE SURE IT'S MORE
VISIBLE.
IT'S DE FACTO WHAT WE'D
RECOMMEND.
I THINK WE'RE ALSO INVESTING THE
PROVIDENCE OF WHAT PEOPLE HAVE
BROUGHT IN AND WHAT'S IT LOOK
LIKE TO BE ABLE TO SHARE BACK
AND COULD BE A VALUABLE
CONTRIBUTOR IN THE CONSENSUS
BUILDING PROCESS.
THEY'RE CONSTANTLY CHANGES.
IT'S CONTINUED TO EVOLVE AND
IMPROVE HOPEFULLY.
I THINK THOSE ARE WAYS WE CAN
CONTRIBUTE BACK TO THE COMMUNITY
AND HELP MAKE BEST PRACTICES BUT
I AGREE WE'RE NOT TRYING TO BE
PRESCRIPTIVE AND SAY YOU MUST DO
IT THIS WAY.
>> WE'RE ALSO EXCITED ABOUT THE
UPCOMING COHORT EFFORTS THAT
WILL OPERATE UNDER A COMMON
PROTOCOL AND IF WE'RE DOING OUR
JOB WELL AND WE'LL SEE IF WE DO
THAT, ESSENTIALLY, COMMUNITIES
ADOPT FRAMEWORKS IF THEY'RE
VALUE DERIVED.
THE MINUTE I CHANGE IT I CAN
ANALYZE MY DATA IN CONTEXT.
ALL THE SUBJECTS INCLUDE.
YOU'RE RIGHT AT THE PRECIPICE OF
DEMONSTRATING THE ADOPTION VALUE
PROPOSITION.
THAT'S MOVING FORWARD.
>> IN THE INTEREST OF TIME WE
CAN ONLY HAVE ONE MORE QUESTION
BUT WE HAVE A TABLE AND IF YOU
HAVE ANY QUESTIONS YOU CAN WRITE
IT DOWN TO HELP ADDRESS IN THE
RESEMP AND APRIL 23 THEY'LL HOST
SO PLEASE JOIN US FOR THAT EVENT
AS WELL.
>> FROM THE UNIVERSITY OF
PITTSBURGH.
I'M A DATA SCIENTIST AND
EDUCATOR AND WE WANT TO INCREASE
THE NUMBER OF DATA SCIENTISTS
THROUGH EDUCATION AND LOOKING AT
THE PLATFORM WITH HARMONIZED
DATA AND WONDERFUL DATA SET, I
WAS WONDERING IF THERE'S AN
OPPORTUNITY FOR EDUCATORS TO USE
THIS PLATFORM FOR EDUCATIONAL
REASONS AND TRANSIT FROM JUPYTER
LAB AND HAVE IT PART OF
EDUCATION.
IS THERE ANYTHING BEING SET FOR
THAT?
>> WE HAVE DONE TRAININGS IN THE
PAST THIS IS THE VALUE OF A
COMMON PLATFORM WHICH OTHERS
USE.
AND AND MAY HAVE ACCESS TO A SET
OF OPEN LEARNING MATERIALS FOR
CAVATICA INCLUDED IN YOUR
PROGRAM
>> A BIGGER AMBITION WOULD BE
DATA SCIENCE TRAINING INNOVATION
GROWS IN THE CONTEXT OF INCLUDE.
CAN WE ESSENTIALLY EXPAND THE
POTENTIAL FOR HOW THE TRAINING
CAN OCCUR THROUGH THE DATA SETS
AND RESOURCES.
AND FOR US IT WILL BE REAL
EXCITING TO INNOVATE WHAT IS
POTENTIAL FOR TRAINING IF YOU
HAVE ACCESS TO THESE RESOURCES,
MULTI-MODAL DATA AND CLOUD
RESOURCE AND COMPUTE
ENVIRONMENTS, PROJECT SPACES.
I THINK THAT'S AN UNTESTED ARENA
IN THE CONTEXT OF TRAINING AND
I'M SURE YOU'LL SEE IT AND WE
SEE IT WRIT LARGE.
DATA SCIENCE IS THE MOST
LIMITING FACTOR IN MOST RESEARCH
ENVIRONMENTS I'M SURE FOR ALL OF
YOU.
IT'S A REAL BARRIER.
PLEASE FOLLOW-UP AND LET'S TALK
ABOUT THIS.
>> THANKS FOR THE GREAT SESSION
AGAIN.
THANK YOU.
>>
>> GOOD AFTERNOON.
THIS IS OUR LAST SESSION BEFORE
THE POSTER BUT WE'LL ENERGIZE
YOU TO TALK TO THE TRAINING
SESSIONS AND WE HAVE 68 POSTERS.
IT'S MY GREAT HONOR TO PRESENT
ON THE TOPIC OF EARLY CAREER
OPPORTUNITIES AND WE HAVE TWO
FANTASTIC SPEAKERS OR THE LAST
SESSION.
THE FIRST SPEAKER IS THE CURRENT
CHAIR OF DEPARTMENT OF
KINESIOLOGY AND HEALTH AT
GEORGIA STATE UNIVERSITY.
AND IN HIS SHORT 16 YEARS OF
CAREER AT GSU HE HAS TRAINED
MANY STUDENTS AND TRAINEES.
HE HAS ALSO RECEIVED AWARDS FOR
HIS MENTORSHIP INCLUDING THE NIH
OFFICE SUPPLEMENT FOR MENTORING.
AND I'M POSITIVE YOU'LL LEARN
FROM HIS IMPACTFUL MENTORSHIP.
THE SECOND IS RESEARCH ASSISTANT
PROFESSOR AT UNC SCHOOL OF
MEDICINE AND THROUGH INCLUDE
FUNDED PROJECTS WE WILL LEARN
WHAT SHE IS DOING TO UNBLOCK
SOME MYSTERIES OF CEREBRAL
SPINAL FLUID DYNAMICS AND
ASSOCIATED NEURAL AND CLINICAL
OUTCOMES IN INFANTS WITH DOWN
SYNDROME.
BACK IN FALL OF 2022, SHE
RECEIVED A FIVE-YEAR NICHD
CAREER DEVELOPMENT AWARD AND WE
WILL HEAR FROM HER AS WELL.
SO THANK YOU TO BOTH SPEAKERS.
I'M HONORED TO SHARE WITH YOU
MY EXPERIENCE IN MENTORING AND
PROVIDING THE YOUNG RESEARCHERS
OPPORTUNITIES AND IDEAS ABOUT
MENTORING.
MY BACKGROUND IS I WAS BORN AND
RAISED IN CHINA AND WENT TO
COLLEGE AND THEN RECEIVED MY
MA
MASTER'S DEGREE IN SHANGHAI.
AND I'VE ENJOYED THE DYNAMIC IN
THE COMMUNITY AND SUPPORTIVE
DOWN SYNDROME COMMUNITY.
AND IN SPRING OF 2021 I RECEIVED
AN EMAIL FROM CHAIR OF THE
AWARDS COMMITTEE AND I NEVER
THOUGHT I'D RECEIVE STUDENT
MENTORING AWARD BECAUSE I FEEL
LIKE I WAS TOO YOUNG.
AND THE AWARD IS FOR MORE
ESTABLISHED RESEARCHER.
THAT AWARD WAS ESTABLISHED IN
2020.
IN 2021 I WAS A SECOND RECIPIENT
CAN'T COMPARE MYSELF TO THE
SECOND RECIPIENT AND I FEEL LIKE
THAT MUST NOT BE TRUE UNTIL MY
WONDERFUL STUDENTS AND
CONGRATULATED ME FOR RECEIVING
THAT AWARD.
I WAS AMAZED AND THRILLED AND
HUMBLED AND THEN REALIZED I NEED
TO LOCK -- LOOK AT THE AWARD
AND READ THE CRITERIA.
I WANT TO READ THOSE TO YOU AND
IT RECOGNIZES THE LONG-TERM
IMPACT OF MENTORING THE CAREERS
OF SCIENTISTS.
SPECIFICALLY LOOKING AT THE
CONTRIBUTION TO WOMEN IN SCIENCE
ENGINEERING, UNDERGRAD STUDENT
EXPERIENCE AND ENGINEERING AND
OUTREACH.
I FEEL LIKE I DID ALL OF THOSE
BUT NOT TO THE LEVEL OF
RECEIVING THE AWARD.
ANYWAY BY LOOKING AT WHAT I HAVE
DONE IN TERMS OF RESEARCH AND
HOW I USED MY RESEARCH AS A
BRIDGE TO MENTOR STUDENTS AND DO
OUTREACH.
I AM ENGINEERING BACKGROUND AND
HAVE AN ENGINEERING BACKGROUND
AND DO BASIC RESEARCH AND
LOOKING AT NEURAL MOTOR
DEVELOPMENT IN CHILDREN WITH
DOWN SYNDROME AND INTERESTED IN
INVESTIGATING THE EFFECTIVENESS
OF PEDIATRIC INTERVENTION AND
FOCUSSED ON THE INFANT
INTERVENTION BY USING DIFFERENT
PARADIGMS.
FOR EXAMPLE, IN TRAINING AND I
FEEL LIKE THESE ARE THE THINGS I
HAVE DONE BUT I DON'T KNOW THAT
WHY THAT LED ME TO THE MENTORING
EXPERIENCE.
I'M LOOKING AT WHAT I'VE DONE
OVER THE YEARS AND CERTAINLY I
HAVE BEEN DEALING WITH
DIVERSITY, EQUITY, INCLUSION AND
ACCESSIBILITY IN RESEARCH
CONDUC
CONDUCTION, STUDENT MENTORING
AND BEYOND.
IN TERMS OF STUDENT MENTORING
AND I WAS FORTUNATE TO HAVE
WORKED WITH DIVERSE STUDENTS AND
I'M WORKING AT GEORGIA STATE
UNIVERSITY IN DOWNTOWN ATLANTA.
IF YOU DO NOT KNOW ATLANTA, I
CAN TELL YOU IT'S PROBABLY THE
MOST DIVERSE CITY POPULATION.
AT GEORGIA STATE WE HAVE MORE
THAN HALF STUDENTS COMING FROM
AFRICAN AMERICAN BACKGROUND.
WE HAVE ASIAN, CAUCASIAN AND
ALSO HISPANIC POPULATION.
WE HAVE EXCELLENT POPULATION OF
STUDENT BODY I WORK WITH AND
ALSO FOR MY OWN GROUP AND I HAVE
MENTORED STUDENTS FROM DIFFERENT
BACKGROUNDS FROM PHYSICAL
THERAPY, MEDICINE, ENGINEERING
ALL KINDS OF YAB BACKGROUND THAT
COME TO ME AND WE CAME TOGETHER
AND FORMED A TEAM AND ONE HALF
OF MY STUDENTS ARE WOMEN
SCIENTISTS OR CLINICIANS AND
GRATEFUL FOR THEIR TRUST IN ME
AND FOR THE WONDERFUL
RELATIONSHIP IN WORKING
TOGETHER.
SO I'M GOING SHARE WITH YOU SOME
OF THE EXPERIENCE I HAD WITH THE
STUDENTS AND CERTAINLY IT'S NOT
INCLUSIVE AND A WANT TO INITIATE
THE CONVERSATION AND SEE WHAT WE
CAN DO TO BRING PEOPLE FROM
DIFFERENT BACKGROUNDS AND WORK
TOGETHER AND ADVANCE SCIENCE.
I WORK WITH EACH STUDENT AND
LOOK AT THE WEAKNESS AND TRYING
TO SITE THEM TO DIFFERENT
PROJECTS.
EACH STUDENT WILL LEAD ONE
PROJECT AND WE'LL BE PART OF THE
MEMBER OF THE OTHER PUBLIC
HEALTH IN TRYING TO CREATE
COHESIVE TEAM AND TO BENEFIT
THEIR OWN GROWTH AND LEARN TEAM
SCIENCE.
AND WE NEED TO LEARN HOW TO DO
TEAM RESEARCH AND SCIENCE AND
GIVE THEM ENOUGH EXPOSURE TO
CONNECT TO POPULATIONS.
DOWN SYNDROME IS ONE I STUDIED
AND I ALSO STUDIED SYNDROMES AND
GENESIS AND CLINICAL POPULATIONS
AND IT'S ONE OF MY FAVORITE.
SO INCLUDES QUESTIONS IN MY
RESEARCH TEAM.
I THINK THAT'S REALLY IMPORTANT
BECAUSE YOU GIVE STUDENTS A
CHANCE TO MENTOR AND TRY TO
LEARN MENTORING SKILLS AND TRY
TO LEARN FROM EACH OTHER THERE'S
A LOT WE CAN LEARN FROM EACH
OTHER.
SO I REALLY THINK THAT WHAT
WORKS FOR ME IS I HAVE GROUP
MEETINGS AND INDIVIDUAL MEETINGS
AND FROM MY PERSPECTIVE AND I
FEEL FROM THE INDIVIDUAL
MEETINGS I REALLY GET TO KNOW
EACH OF MY STUDENTS AND
UNDERSTAND WHERE THEY STRUGGLE
AND WHAT THEY'RE PROUD OF AND
YOU HAVE TO BE PATIENT AND MAKE
AND THEY FOUND A SOLUTION TO
SOLVE PROBLEMS AND SO IT'S
NOBODY'S FAULT BUT WE NEED TO
UNDERSTAND EACH OTHER AND KNOW
WHAT WE NEED TO FOCUS ON AND SET
A REASONABLE TIME LINE AND
THAT'S REALLY IMPORTANT.
AND ONE MIFF STUDENTS TOOK
MATERNAL LEAVE AND THAT WAS NOT
THE PLAN BUT IT HAPPENED AND WE
HAVE TO HAVE TIME FOR HER TO
TAKE CARE OF HER FAMILY AND THEN
GET BACK TO RESEARCH AND THAT'S
SOME THINGS WE NEED TO
UNDERSTAND AND PROVIDE A
SOLUTION AND REPORT AND IT COMES
FROM OTHER'S TRUST AND LEARN
WHERE YOU STRUGGLE AND HOW YOU
CAN SUPPORT AND I THINK WHEN
THEY CAME TO MY LAB IT DIDN'T
FEEL LIKE MUCH AT ALL AND
THERE'S TIME TO WORK TOGETHER,
FOUR, FIVE YEARS AHEAD IF WE
HAVE A GOOD PLAN BY THEN OF THE
DOCTORAL STUDY AND YOU SHOULD BE
PROUD OF YOURSELVES BECAUSE
YOU'RE EQUIPPED WITH MOVING TO
THE NEXT LEVEL.
AND I'M PROUD TO SAY THAT MOST
OF MY DOCTORAL STUDENTS LANDED
THEIR FIRST GROP UPON GARAGE
WEIGHING AND ARE PROUD OF
THEMSELVES AND MYSELF.
AND THE OTHER THING I DID I
THINK AS A RESEARCHER WE ALL
FOCUSSED ON RESEARCH BUT AT THE
UNIVERSITY WE ALSO HAVE
INSTRUCTORS TO RESIDENTS AND
NEED TO TAKE CARE OF THE
UNDERGRAD, GRADUATE STUDENTS.
REMEMBER YOU CAN BRING
INTERESTING TO THE UNDERGRAD
CLASSES AND BEING PATIENT WITH
STUDENTS AND UNDERSTAND SOME
COME FROM UNDER REPRESENTED
BACKGROUNDS AND DON'T HAVE GOOD
MATH SKILLS OR VERY GOOD SKILLS
AND TO SURVIVE CLASSES YOU NEED
TO DEVELOP STEPS AND PROCEDURES
TO HELP THEM AND INTRODUCE
RESEARCH OPPORTUNITIES AND THEY
FEEL LUKE IT'S OUT OF REACH FOR
THEM BUT IF YOU LEARN MORE THEY
CAN DO SOMETHING FOR YOU AND BE
PROUD OF THE TEAM.
AT OUR UNIVERSITY AND WE HAVE
PROGRAMS AND WE HAVE IN MY
DEPARTMENT WE HAVE RESEARCH
INTERNSHIP AND WE HAVE UNDERGRAD
SUMMER SCHOLAR PROGRAM.
THEY CAN APPLY FOR THE PROGRAM
AND GET WHOLE SUMMER WORKING
WITH RESEARCHERS AND UNDERSTAND
DEVELOP RESEARCH SKILLS AND LOOK
AT OPPORTUNITIES AND LET ME GIVE
AN EXAMPLE AT THE AMERICAN
SOCIETY OF BIO MECHANIC.
A UNIQUE PROGRAM WAS ESTABLISHED
CALLED BE SURE TO STIPULATE THE
INTEREST FROM UNDERGRAD STUDENTS
TO DO RESEARCH AND AGAIN THEY
GET FINANCIAL SUPPORT TO WORK
WITH OUTSTANDING RESEARCHERS IN
THE FIELD FOR A WHOLE SUMMER AND
YOU CAN LEARN IF THAT IS THEIR
PASSION FOR THE RESEARCH, I
THINK THEY'RE WONDERFUL
OPPORTUNITIES.
AS A RESEARCHER WE FOCUS ON WHAT
WE DO AS A RESEARCH BUT I THINK
THERE'S SOMETHING BEYOND THAT
AND WE CAN REALLY LOOK AT THE
PIPELINE TO GET YOUNGER
UNDERGRAD STUDENTS IN THE
PIPELINE AND TRADE THEM AND TO
PREPARE THEM FOR THE NEXT
GENERATION OF RESEARCHERS.
ONE IDEA FOR THE NATIONAL
OUTREACH IS I ESTABLISHED A
STUDY ABROAD PROGRAM AND SO I
JUST WANT TO PROVIDE AN
EXPERIENCE AND KNOW WHAT IS OUT
THERE AND WE HAVE COLLABORATION
IN CHINA AND SO BASICALLY THAT
IS AND MOST STUDENTS WENT OUT OF
THE COUNTRY FOR THE FIRST TIME
AND IT'S AN EXPERIENCE FOR THEM
TO GET TO KNOW SOME PEOPLE AND
STUDENTS AND TAKE CLASSES WITH
PROFESSORERS AND EYE OPENING
EXPERIENCE FOR THEM AND ALONG
THE WAY, I KIND OF INTEGRATE MY
RESEARCH INTO THE CONVERSATION
WITH THEM.
I'LL SAY HERE'S WHAT I DO AND
NOTHING TO DO WITH THE STUDY
ABROAD PROGRAM BUT HERE'S WHAT I
DO AND WANT TO INTRODUCE THAT
AND IT KIND OF STIMULATED THAT
PROGRAM AND HOW CAN THIS BE
INCORPORATED TO THEIR OWN AND I
CANNOT GUARANTEE THAT EVERYBODY
WILL GO TO MEDICAL SCHOOL OR DO
RESEARCH AND I THINK THAT IS
MUCH BROADER IMPACT AND PROVIDE
TO THE UNDERGRAD EDUCATION AND I
FEEL LIKE THAT IS AN EXCELLENT
OPPORTUNITY.
I'M GRATEFUL I RECEIVED
DIVERSITY SUPPLEMENT TO SUPPORT
MY ONGOING RESEARCH PROJECT.
AND THIS ALLOW MED TO RECRUIT
UNDERGRAD STUDENTS.
I WAS NOT VERY BRAD AT
RECRUITING DOCTORAL STUDENTS I
KNOW I HAD PLENTY TO CHOOSE
THERE BUT WAS ABOUT TO RECRUIT
VARIOUS STUDENTS.
I SENT THEM OUT TO UNDERGRAD
STUDENTS IN MY DEPARTMENT AND
SAID THERE WERE TWO POSITIONS
AND AVAILABLE AND RECEIVED 18
APPLICATIONS.
I NEED TO CHOOSE ONE OUT OF NINE
FOR THAT AWARD AND I GOT SO MANY
AND I MADE JUDGMENT TO THE
BUDGET AND IF YOU'RE LOOK AT THE
DEMOGRAPHIC BREAKDOWN.
AND I HAVE HISPANIC MALE AND
FEMALE AND I TRIED TO DO
OUTREACH AND RECRUIT EXCELLENT
STUDENTS AND ESPECIALLY UNDER
REPRESENTED STUDENTS INTO MY
RESEARCH AND TRIED TO PROVIDE
THEM AND RESEARCH TRAINING AND
HOPEFULLY THEY CAN STAY ON TRACK
AND BECOME THE NEXT GENERATION
OF RESEARCHERS.
THIS HELPED ME SUMMARIZE WHAT I
DID AS A MENTOR.
I THINK EVERYBODY IS PROBABLY
MOST RESEARCHERS IN THE ROOM
HAVE DONE THIS AND TO SUMMARIZE
WHAT I DID AND GET INVOLVED IN
RECRUITMENT AND OUTREACH AND
TRAINING FOR DATA ANALYSIS AND
DATA COLLECTION AND ATTENDING
THE RESEARCH SEMINARS AND
PRESENTING AT CONFERENCE AND
TRAINING AT WRITING AND ALSO
PROMOTE DIVERSITY AND
ACTIVITIES.
AND BECAUSE THEY'RE PART OF THAT
DIVERSITY SUPPLEMENT AND THEY
SHOULD ACTUALLY REACH OUT AND
TALK ABOUT WHAT THEY LEARNED AND
TO CONVEY THAT AND SPREAD THAT
OUT TO THE KNOWLEDGE AND
INFORMATION TO OTHER PEOPLE.
MY HUMBLE EXPERIENCE TOLD ME I
HAVE TO BE NICE, PATIENT,
GRATEFUL AND OPEN MINDED.
I WANT TO USE THIS AT THE BOTTOM
IMAGE TO SHOW THIS IS MENTORING
LATE LETTER AT THE FINAL.
I THINK I'M IN THE MIDDLE NOW.
AND HOW I MOVED TO THE TOP IS
ALL LEARNING EXPERIENCE AND WE
WERE NOT BORN WITH ALL THE
KNOWLEDGE ABOUT STUDENT
MENTORING BUT YOU LEARN A LOT OF
WAYS AND I'M GRATEFUL I HAVE MET
SO MANY EXCELLENT MENTORS AND
TRYING TUESDAY MY EXPERIENCE TO
MENTOR THE NEXT GENERATION OF
RESEARCHERS AND I WANT TO
SOMETHING TO UNDER REPRESENTED
STUDENTS IN THE AUDIENCE.
YOU HAVE TO THINK BIG AND HIGH.
RIGHT NOW I'M THE CURRENT SHARE
AND I NEVER THOUGHT I'D BECOME
CHAIR AND IT HAPPENS.
AND AND THE TIME IS TIME
CONSUMING BUT YOU CAN USE THE
POSITION TO BENEFIT AND PROVIDE
SUPPORT TO MANY FACULTY, STAFF,
STUDENTS TO MOVE THE WHOLE
PROGRAM AND DEPARTMENT FORWARD
AND ESTABLISH A WONDERFUL
PARTNERSHIP AND CONNECTION WITH
LOCAL COMMUNITIES.
SO YOU DO SOMETHING BEYOND WHAT
YOU DO AS A RESEARCHER AND YOU
CAN REALLY PROMOTE SOMETHING BIG
AND SO THAT'S THE MESSAGE I WANT
TO GIVE TO YOUNG GENERATION AND
IF AN OPPORTUNITY ARISES DON'T
BE SHY BECAUSE THEY CAN BE
WONDERFUL OPPORTUNITIES.
SO CERTAINLY YOU WILL SACRIFICE
YOUR OWN RESEARCH TO A CERTAIN
DEGREE.
BUT YOU CAN PROVIDE MUCH BIGGER
IMPACT TO YOUR PROGRAM,
STUDENTS, YOUR INSTITUTION IN
SOCIETY.
AND WITH THAT, I WANT TO
CONCLUDE ONE MY TALK WITH THE
TWO PICTURES THAT WERE TAKEN 10
YEARS A PART.
YOU CAN SEE I SORT OF REALLY
MATURED OVER THE THREE YEARS BUT
THE BOLT BOTTOM RIGHT WAS TAKEN
LAST YEAR AND WE HAD A WONDERFUL
TIME IF YOU IGNORE THE MESS AT
THE TABLE AND JUST LOOK AT THE
SMILES WE HAD WE REALLY ENJOYED
OURSELVES AND MADE IT A
WONDERFUL REUNION AND TO KEEP
REMINDING US WE WERE IN THE SAME
BOAT AND ARE GOING TO WORK
TOGETHER AGAIN IN THE FUTURE.
THANK YOU.
>> HELLO.
I'M DR. DERICK FROM UNC CHAPEL
HILL AN EXCITED TO GIVE YOU AN
OVERVIEW OF MY EDUCATION AND
TRAINING TRAJECTORY AND THE ROLE
MENTORSHIP PLAYED IN MY CAREER
AS WELL AS A LITTLE SNEAK PEEK
INTO ANY INCLUDE FUNDED PROJECT
LOOKING AT C N DYNAMICS IN
CHILDREN WITH DOWN SYNDROME.
MY EDUCATION TRAJECTORY STARTED
AT THE UNIVERSITY OF FLORIDA
WHERE I GOT MY BACHELOR'S OF
SCIENCE I HAVE THE GREAT
PRIVILEGE OF BEING ABLE TO
PARTICIPATE IN RESEARCH MANY
LABS AND MULTIPLE UNIVERSITIES
DURING MY FOUR YEARS.
THERE'S ONE MENTOR WHO MADE THE
BIGGEST IMPACT DR. SCOTT MILLER.
I SPENT THREE AND A HALF YEARS
BEING A RESEARCH ASSISTANT IN
HIS LAB AND WHILE HE DID A GREAT
JOB IN CHILD PSYCHOLOGY AND
CHILD DEVELOPMENT, I THINK WHAT
I TOOK AWAY IS HOW TO THINK
ABOUT RESEARCH.
ME MENTORED MY HONOR THESIS AND
SPARK AN INTEREST THAT SPARK THE
REST OF MY ACADEMIC CAREER.
ONE QUALITY THAT REALLY STUCK
OUT ABOUT HIM WAS HE FOSTERED
ANY INDIVIDUAL INTERESTS I HAD
AND WHEN I HAD ONE OUT OF HIS
SPOKE WHICH WAS OFTEN AT 19, HE
ENCOURAGED ME TO SEEK OUT OTHER
LABS AND THAT HELPED ME LEARN
ABOUT NOT ONLY OTHER RESEARCH
APPROACHES BUT GAIN EXPERIENCE
IN OTHER LABS IN ORDER TO LEARN
WHAT LAB STRUCTURE AND MENTORING
STYLE WORKS BEST FOR ME AND
SOMETHING I STILL ENCOURAGE
GRADUATE STUDENTS AND UNDER
GRADS TODAY.
IT'S ONE OF THE MOST IMPORTANT
THINGS ABOUT FINDING A RESEARCH
TEAM IS A GOOD FIT ON TOP OF
EVERYTHING ELSE.
ALL THOSE EXPERIENCE PREPARED ME
WELL TO CHOOSE A GRADUATE
PROGRAM.
I ENDED UP GOING TO FLORIDA
INTERNATIONAL UNIVERSITY FOR MY
MASTER'S Ph.D. AND UNDER
UNDERGRAD I WAS CERTAIN I WANTED
TO DEVOTE MY CAREER TO LOOK AT
CHILD DEVELOPMENT AND NEXT STEP
WAS CHILD DEVELOPMENT AND CHOSE
ANTHONY DICK AS ANY TRAINING
MENTOR AND GIVE THEM CREDIT
BECAUSE I HAD ZERO EXPERIENCE IN
NEUROSCIENCE AND HE TOOK A BIG
RISK AND TRAINED ME FROM THE
GROUND UP.
ACROSS THE FIVE YEARS I LEARNED
ABOUT NEURO IMAGING AND BRAIN
DEVELOPMENT AN GOT TO WORK ON A
FEW FUN PROJECTS.
I LEARNED HOW TO MAP OUT
NEURONAL DENSITY IN CHILDREN AND
ADULTS AND WENT TO MAPPING THE
STRUCTURAL CONNECTOME OF THE
BRAIN.
DURING THE PROJECTS AND LOOKING
AT CLINICAL IMPLICATIONS WHICH
ARE THE NEXT STEP OF NEURAL
IMAGING.
WHAT'S IT MEAN FOR A CLINICIAN
OUTSIDE THE LAB?
I NEEDED MORE CLINICAL TRAINING.
UP TO THAT POINT EVERYTHING I'VE
DONE IS NORMATIVE TRAJECTORIES
AND I NEEDED ADDITIONAL CLINICAL
TRAINING TO DRAW THE
IMPLICATIONS.
AND A CLINICAL PSYCHOLOGIST THAT
STUDIES YOUNG CHILDREN WAS A
CO-MENTOR AND I HAD A CLINICIAN
TO HELP ME DRAW THE CONCLUSIONS.
AND DURING THE LAST YEAR OF
GRADUATE SCHOOL I GOT TO
COLLABORATE ON VERY FUN PROJECTS
LOOKING AT BIOMARKERS AND NEURO
IMAGING FOR ADHD SYMPTOMS AND
FIBER TRACTOGRAPHY TO TRACT
TRAITS.
I KNEW BY THE END OF MY Ph.D. I
NEEDED MORE.
AFTER ONE YEAR OF CLINICAL
TRAINING I KNEW I WANTED TO LOOK
INTO POSTDOC TRAININGS TO ALLOW
ME TO EXPAND THIS.
I WAS INTERESTED IN NEURAL
DEVELOPMENTAL DISORDERS AND
BEING ABLE TO DOWNWARD EXTEND MY
EXPERIENCE IN NEURAL IMAGING AND
GOT INTERESTED IN WHAT IT WOULD
BE LIKE TO SCAN AN INFANT BEFORE
SYMPTOMS APPEAR.
THAT'S WHAT STUCK OUT TO ME
ABOUT UNC CHAPEL HILL.
I END UP IN A POSTDOC THERE AND
PURSUED A T32 SCHOLARSHIP IN
NEURAL DEVELOPMENTAL DISORDERS
BY NICHD AND I CANNOT RECOMMEND
THEM ENOUGH.
THEY'RE AN EXCELLENT RESOURCE
BECAUSE UNLIKE A TRADITIONAL
POSTDOC WHERE YOU TAKE ON A FULL
TIME JOB AND JOIN A LAB, A T32
IS A COMBINATION OF TRAINING AND
RESEARCH.
I HAD DIDACTIC TRAINING WITH
COURSE WORK AND HANDS-ON
EXPERIENCE IN A LAB AS WELL AS
SCANNER WHICH GAVE ME A WIDE
BREADTH OF EXPERIENCE IN JUST
TWO YEARS OF TIME.
I DECIDED TO FOLLOW A
CO-MENTORSHIP MODEL SINCE I TOWN
IT WORKED WELL FOR ANY
DISSERTA
DISSERTATION.
THE MORE SPEEDBACK YOU GET IT
CAN GIVE YOU -- FEEDBACK GIVES A
UNIQUE PERSPECTIVE WHEN YOU
COMBINE PEOPLE FROM OTHER AREAS
OF EXPERTISE.
I WORKED WITH A CLINICAL NEURAL
SCIENTIST AND DOES TRANSLATIONAL
NEURAL SCIENTIST AND A RENOWN
PSYCHIATRIST AND EXPERT IN
AUTISM.
I'LL GIVE A BRIEF OVERVIEW OF
CSF DYNAMICS AND PIMPLICATIONS.
CEREBROSPINAL FLUID IS GET
ATTENTION DUE TO THE REDISCOVERY
OF THE LYMPHATIC SYSTEM.
THE ROLE OF CSF IN THE BRAIN IS
TO BE A WASTE CLEARANCE PATHWAY
AND NOT ONLY DISTRIBUTE THOSE
GROWTH FACTORS TO THE BRAIN BUT
REMOVES AMYLOID BETA.
GIVEN THE ASSOCIATION WITH IT
THIS ALMOST ALL RESEARCH LOOKED
AT THIS IN ALZHEIMER'S.
THERE'S A LARGE GAP IN
UNDERSTANDING WHAT THEY LOOK
LIKE IN EARLY LIFE.
OUR LAB AT UNC LOOKED AT THIS IN
INFANCY AND WHAT YOU SEE IN THE
BOTTOM THREE BRAINS IS INFANT
WHO WENT ON TO DEVELOP AUTISM
AND THEN SEE A TYPICALLY
DEVELOPING INFANT.
THE THING THAT JUMPS OUT IS THE
EXTRA AXIAL CSF.
WHAT WE SEE IS AN INCREASE OF
CSF ACCUMULATING AS EARLY AS SIX
MONTHS OF AGE, YEARS BEFORE
TYPICAL SYMPTOMS APPEAR.
THAT'S NOW BEEN REPLICATED AMONG
THREE STUDIES AND COHORTS AND
HAPPENS TO BE VERY REPLY --
REPLICABLE AND I LOOKED AT CSF
DYNAMICS.
I HAD A RECENT PAPER WHERE I
LOOKED AT VASCULAR SPACES WHICH
SEE AN ANIMATION OF HERE.
THEY'RE TYPICALLY VIEWED AS
MARKERS OF VARADIATION.
IT'S A SIGN OF BRAIN AGING.
THE STUDY SHOWED ALMOST HALF OF
2-YEAR-OLD GOOD ON TO DEVELOP
AUTISM HAVE LARGE PBS BY THE
TIME THEY'RE 24 MONTHS OF AGE
AND AN EARLY BIOMARKER OF THE
DISORDER.
WHEN PUT THAT TOGETHER WE'RE
SAYING AN ACCUMULATION OF CSF
AND HAVE EVIDENCE OF IMPAIRED
CSF FLOW.
WE HAVE AN OVER ALL NARRATIVE OF
DYNAMICS IN AUTISM.
IS THIS AUTISM SPECIFIC?
AUR TEAM THINKSES -- THINK NO.
WE THINK THERE'S SHARED
PATHOPHYSIOLOGY.
WE LOOKED AT SYNDROMES, FOR
EXAMPLE, FRAGILE X WHERE WE SEE
THIS AT THE TOP WHAT YOU SEE IS
THAT INFANTS NOT ONLY HAVE MORE
EACSF BUT MORE THAN AUTISM AS
WELL.
WE ALSO SEE THE PATTERN IN
FRAGILE X AS WELL.
ALL THIS PUT TOGETHER MEANS IT'S
MOST LIKELY NOT AUTISM SPECIFIC
AND BASICALLY AN ABNORMAL
PATHWAY AND A SIGN NEURAL
DEVELOPMENTAL DISORDER TAKING
PLACE BRINGING ME TO THE MOST
EXCITING PEOPLE AND THEY'RE
LOOKING AT THE DYNAMICS TO DOWN
SYNDROME DON'T HAVE TO TELL THIS
AUDIENCE BUT IT'S A MODEL TO
EXAMINE CSF DYNAMICS AND HAVE
EARLY ONSET ALZHEIMER'S,
INDIVIDUALS WITH DOWNS SYNDROME
ARE 15 TIMES MORE LIKELY TO
DEVELOP AUTISM.
SO WITH A COMBINATION OF RISK
FOR AUTISM AND ALZHEIMER'S, WE
HAVE REASON TO BELIEVE THERE'S
DYNAMICS AT PLAY.
SO I USE INCLUDE FUNDING.
I'M DOING A FIVE-YEAR STUDY TO
EXAMINE CSF TRA JEJECTORIES TO K
AT INTERIM BIOMARKERS AND
THERAPEUTICS INTRAFECAL
THERAPEUTIC REQUIRE A KNOWLEDGE
OF CSF DYNAMICS.
RIGHT NOW IT'S ALMOST EXCLUSIVE
TO ADULTS.
AND THAT I HAVE A CAREER
DEVELOPMENT AWARD MENTIONED
FUNDED BY INCLUDE NICHD.
AND I GET TO COMBINE NOT ONLY MY
FIVE-YEAR RESEARCH PROJECT BUT
ALSO FIVE YEARS OF EXTENSIVE
TRAINING.
I'M USING THIS TRAINING TIME IN
ORDER TO EXPAND CLINICAL AND
PRE-CLINICAL TRAINING.
AND NOW I WORK WITH INDIVIDUALS
WITH DOWN SYNDROME AND FOR THE
FIRST TIME I'M TRYING TO SPEND
EYE -- A DECENT AMOUNT OF TIME
WITH PRE-CLINICAL TRAINING AND
MOUSE MODELS ARE IMPORTANT IN A
NOVEL FIELD FOR ME.
I'VE BEEN SPENDING TIME BEING
TRAINED IN THAT SO DO MORE
COLLABORATORY WORK AND I'M
LOOKING AT CSF DYNAMICS ACROSS 6
TO 24 MONTHS IN INFANTS WITH
DOWN SYNDROME TO RELATE IT TO
LATER NEURAL OUTCOMES PRIMARILY
WHITE MATTER AND NEURAL DENSE
SI.
IF YOU'RE INTERESTED I HAVE A
POSTER TODAY AT 3:30.
MORE INFORMATION ON THAT.
AND I'M ALSO TO LOOK AT CSF IN
RELATION TO CLINICAL OUTCOMES
AND MOTOR AND COGNITIVE AND
SLEEP OUTCOME.
AND I HAVE A GREAT TEAM WHO
AGREED TO HELP ME IN THE
PROCESS.
FAMILIAR NAME I BROUGHT UP HAVE
CONTINUED BEING MY POSTDOC
MENTORS TO MY K1 MENTORS AND
I'VE ALSO ADDED A CO-MENTOR WHO
IS A CREDITED TO BE ONE OF THE
CO-DISCOVERIES OF THE SYSTEM AND
HE'S A CSF EXPERT AND WORKS IN
THE ALZHEIMER'S FIELD AND IS
PURELY A PRE-CLINICAL SCIENTIST
SO HE WORKS PRIME IERL WITH
RODENT MODELS AND THROUGH
INCLUDE FUNDING I HAD THE
PRIVILEGE OF SPENDING FOUR WEEKS
IN HIS LAB IN THE UNIVERSITY OF
WASHINGTON WITH TRAINING IN HIS
V.A. LAB TO LOOK AT HOW CSF
STUDIES HAVE DONE IN RODENTS
HELPING SHAPE THE QUESTIONS WE
ASK AND IT'S DIFFERENT SEEING IN
AN ANIMAL THAN MAKING
ASSUMPTIONS BASED ON MRI.
AS THE BEEN A VERY HELPFUL
EXPERIENCE.
AND THE CSF OF DYNAMICS ARE
ABERRANT IN PEOPLE WITH WHO
DEVELOP DOWN SYNDROME AND THIS
WILL BE THE FIRST STUDIO TO USE
HIGH ORDER DIFFUSION MODELS AND
LOPE LOOK AT DISEASE PROGRESSION
AND TARGETED THERAPEUTICS.
ONE OF THE BIGGEST THINGS I WANT
IT LEAVE YOU WITH IS WHILE I
FEEL VERY FORTUNATE TO HAVE HAD
THE FOUNDATIONAL TRAINING I'VE
HAD, I THINK IT'S THE PEOPLE
THAT MADE THE LARGEST IMPACT
ALONG THIS WAY STARTING FROM MY
GRADUATE LAB WHO I STILL HAVE
THE PLEASURE OF SEEING AT ALMOST
EVERY CONFERENCE I GO TO AND
FEEL FREE TO ASK PEOPLE OUTSIDE
YOUR LOOK AT YOUR SPECIFIC AIMS
AND SOMEBODY WHO IS NOT IN YOUR
FIELD CAN GIVE VALUABLE FEEDBACK
ON THE IMPLICATIONS AND IT'S
IMPORTANT TO GET FEEDBACK FROM
THOSE NOT IN YOUR FIELD AND
SMALL AND LARGE NETWORKS MADE A
HUGE IMPACT ON MY WORK.
I JUST MADE THESE QUICK OVERVIEW
OF THE MENTORSHIPS.
ONE BIG THING IS SEEK OUT
MENTORS SUPPORTIVE OF GROWING
INTERESTS.
I HIGHLY RECOMMEND CO OR
MULTI-MEMBE
MULTI-MEMBERSHIP MODELS AND NOT
LIMIT YOURSELF GEOGRAPHICALLY
AND MAKE MENTORSHIP WORK ACROSS
UNIVERSITIES AND DISTANCES.
I PLAN TO TAKE ALL OF THE WORK
I'M DOING NOW AND USE IT FOR
PRELIMINARY DATA FOR A RO1 OR
TWO AND HUGE SHOUT OUT TO THE
FAMILIES AND INFANTS WHO
CONTINUE TO PARTICIPATE AND
COLLABORATORS WHO CONTRIBUTED TO
EVERYTHING WE'VE DONE SO FAR.
THANK YOU.
>> THANK YOU TO DR. GEHRIG AND
WU AND I WANT TO KNOW HOW MANY
IDENTIFY AS STUDENTS, TRAINEES,
GRADUATE STUDENTS, POSTDOCS?
AND HOW MANY HAVE GRADUATES AND
TRAINEES IN YOUR LAB?
THIS IS RELEVANT TO EVERYONE IN
THE ROOM.
I KNOW WE ARE CUTTING CLOSE TO
THE TIME SO I AM ONE OF THE
PROGRAM DIRECTORS AT NICHD AND A
MEMBER OF THE INCLUDE PROJECT
TEAM.
AND YOU INTEREST TRAINEES AND
INVESTIGATORS IN THE DOWN
SYNDROME ECO SYSTEM.
AND THIS IS A GREAT TOOL FROM
NIH.
THESE ARE RECEIVERS FOR
UNDERGRADUATES AND GRADUATE
STUDENTS, POSTDOCS, EARLY CAREER
TRAINEES AND INVESTIGATORS AND
HAVE INITIATIVES AND MECHANISMS.
I WILLING GIVE A SUMMARY OF THE
NIH ALPHABET SOUP FOR MECHANISMS
BUT NOT ALL AND IT'S A GREAT
RESOURCE AND WE HAVE THE INCLUDE
WEBSITE WHERE WE POST ANY
FUNDING OPPORTUNITIES THAT WE
PUBL
PUBLISH.
THESE ARE TWO GREAT RESOURCES.
THIS INFO GRAPHIC TAKES US
THROUGH THE CAREER STAGES OF
TRAINEES START FROM
UNDERGRADUATE TO GRADUATE AND
POST-DOCTORAL AND RESIDENCY AND
THEN EARLY CAREER AND FINALLY TO
INDEPENDENT POSITION.
AND THERE'S MECHANISMS NIH USES
TO SUPPORT TRAIN JAEES AND A NUR
OF MECHANISMS THROUGH INCLUDE AS
WELL.
I WANTED TO SAY IF THERE'S A
MECHANISM THAT INCLUDE DOES NOT
OR HAVE YOU CAN STILL APPLY TO
ANY NIH PARENT FUNDING
OPPORTUNITIES AND IF IT HAS A
DOWN SYNDROME FOCUS, THERE MAY
BE OPPORTUNITIES TO BE FUNDED
THROUGH INCLUDE.
AND LEAD TO A GRADUATE AND
DOCTORAL PROGRAM AND R
MECHANISMS AND FELLOWSHIP
MECHANISMS TO SUPPORT THAT
CAREER STAGE.
THERE'S TRANSITION AWARDS AND
THERE'S OTHER MECHANISMS SUCH AS
YOUR KO1s YOU HEARD DR. DERRICK
TALK BAND D43 AND QUESTION IN
THE EARLIER SESSION ABOUT
TRAINEES AND LOW AND MIDDLE
INCOME COUNTRY.
WE HAVE A FEW MECHANISMS TO
SUPPORT THOSE AS WELL.
AND THE EARLY CAREER MECHANISM
SUCH AS THE K22s AND R25 AND OF
COURSE YOU TRANSITION TO AN UP
INDEPENDENT POSITION.
AND YOU HEARD ABOUT THE
DIVERSITY SUPPLEMENTS.
DIVERSITY SUPPLEMENTS ARE
ADMINISTRATIVE SUPPLEMENT REZ
VIEWED INTERNALLY AND USED TO
DIVERSIFY THE BIOMEDICAL
WORKFORCE AND COULD BE APPLIED
THROUGHOUT THE CAREER TRAJECTORY
AND HAS TO BE AN ACTIVE PARENT
AWARD FOR DIVERSITY SUPPLEMENTS.
SO MOST REQUIRE U.S
U.SU.S. EXCELLCITIZENSHIP
AND THERE'S SOME MECHANISM ALLOW
NON-U.S. CITIZENS THAT APPLY.
THIS IS THE R52 INCLUDE HAS R25
SPECIFICALLY FOCUSSED ON
PROVIDING CLINICAL RESEARCH
EXPERIENCE FOR GRADUATE AND
MEDICAL STUDENTS AND MEDICAL
RESIDENTS, POSTDOC AS EARLY
CAREER FACULTY TO ASHORT COURSE.
THIS WAS RECENTLY PUBLISHED AND
IN CASE THE ONE CARRIER THAT IS
NOT INCLUDED IS UPPER,
UNDERGRADUATE STUDENTS.
NICHD HAS AN R52.
AS SAID, FIT DOESN'T HAVE A
PARTICULAR MECHANISM, ONE OF THE
I.C.s MAY HAVE A PARENT OR NIH
MAY HAVE A PARENT THAT ONE CAN
APPLY TO.
OF COURSE NEUROSCIENCE HAS A
DIVERSITY FOCUSSED R25 AND HEARD
FROM OTHERS ABOUT THE DATA
SCIENCE FOR THE DS3 PROGRAM THAT
CONTINUE AND FOCUSSING ON
INCREASING DATA SCIENTISTS FOR
THE FIELD.
THE NEXT ARE INDIVIDUAL
FELLOWSHIPS FOR PRE-DOCS.
NIH HAS SEVERAL STANDING
PREDOCTORAL FELLOWSHIPS FOCUSSED
ON WHAT IS YOUR DEGREE AND WHERE
YOU ARE IN THE CAREER
TRAJECTORY.
THERE'S F30s AND F31 AND
SPECIFIC F31 DIVERSITY
FELLOWSHIP.
IF THERE'S ANY ONE TAKEAWAY OF
MESSAGE FROM MY PRESENTATION IS
THAT PLEASE CONTACT YOUR PROGRAM
OFFICER.
IF THERE'S ANY QUESTION, THEY
ARE AVAILABLE TO GIVE YOU --
SEND YOU RESOURCES THAT YOU WILL
NEED.
SO THERE ARE A LOT OF FUNDING
OPPORTUNITIES YOU NEED TO HAVE
THE INFORMATION AND PLEASE REACH
OUT TO YOUR PROGRAM OFFICERS.
ONE OF MY FAVORITE AWARDS ARE
PHASED AWARDS.
THIS IS RELATIVELY NEW AND
THEY'RE CLOSE TO DISSERTATION.
AND THEN THEY CAN TRANSITION
INTO A POSTDOC CAREER, PHASE FOR
THREE TO FOUR YEARS OF FUNDING.
THEY DON'T HAVE TO IDENTIFY A
LAB IN THAT APPLICATION.
IT HAS TO BE FOCUSSED ON DOWN
SYNDROME.
IT'S A GREAT MECHANISM AND THE
BRAIN INITIATIVE HAS THE SAME
BUT FOCUSSED ON DIVERSITY.
INDIVIDUALS CAN APPLY THAT.
YOU HEARD A LITTLE BIT ABOUT THE
MENTORED CAREER DEVELOPMENT
AWARDS INCLUDE HAS A NOTICE OF
SPECIAL INTEREST.
THIS IS AN ALPHABET SOUP OF Ks.
DIFFERENT CAREER POINTS OF
SOMEONE'S CAREER AS WELL AS A
MENTORED PATIENT ORIENTED
RESEARCH CAREER THE K23.
THERE'S A MOSAIC K99, K00 THAT'S
AN INTERESTING AWARD TO PROMOTE
DIVERSITY.
AND FOR THE INTERNATIONAL
TRAINEES IN LOW AND MIDDLE
INCOME COUNTRIES THERE'S THE K43
WHICH IS EMERGING GLOBAL LEADER
AWARD AND FOCUSSED ON CAPACITY
BUILDING IN THE LOW AND MIDDLE
INCOME COUNTRIES.
THERE'S K01 FOCUSSED ON
INTERNATIONAL RESEARCH
SCIENTISTS DEVELOPMENT AWARD.
AND OF COURSE WE ARE ALSO
FUNDING THE NCATS CLINICAL
TRANSLATIONAL AWARD PROGRAM AND
SUPPORTING THE KL2 CAREER
DEVELOPMENT AND INCLUDE IS
FUNDING THIS AWARD TO FOSTER A
PATHWAY FOR INVESTIGATORS IN THE
DOWN SYNDROME SPACE.
THE LAST SLIDE FOR THAT
TRANSITION TO AN INDEPENDENT
CAREER AGAIN WE HAVE THAT PHASED
AWARD AND THE K99, R00 HAD FOR
INDEPENDENCE AND SUPPORTING THAT
IS ALSO THE F32s WHICH ARE
INDIVIDUAL SERVICE AWARD POVLT
DOCTORAL FELLOWSHIP.
-- POST-DOCTORAL AWARD
FELLOWSHIP.
THERE'S THE LOAN REPAYMENT
PROGRAM.
IT'S A FANTASTIC PROGRAM.
WE KNOW ONE OF THE BARRIERS OF
RESEARCH TO CONTINUE ARE STUDENT
LOANS.
SO HAD A ROBUST SUCCESS RATE IN
THE FUNDING CYCLES, 53% OF
APPLICANTS WERE AWARDED.
THIS IS RESTRICTIVE TO
U.S. CITIZENS.
SO WE HEARD FROM BOTH DOCTOR WU
AND GARRICK AND BEHIND EVERY
SUCCESSFUL TRAINEE IS A MENTOR.
NIH LAUNCHED THIS CHIEF OFFICER
OF SCIENTIFIC WORKFORCE
DIVERSITY OFFICE.
AND THROUGH THIS OFFICE THEY
PILOTED THIS MENTORING
SUPPLEMENT.
THIS WAS A SUPPLEMENT FOR
EXISTING PARENT AWARDS.
THE 2022 APPLICATIONS WERE VERY
COMPETITIVE AND WE WERE PLEASED
ONE OF OUR INCLUDE DOWN SYNDROME
INVESTIGATORS RECEIVED THIS
SUPPLEMENT.
THAT'S WHERE I WILL END.
I THANK THE TWO SPEAKERS AND
DR. GARRICK MAKING THE FLIGHT
AND I APPRECIATE HER MAKING IT
HERE TODAY.
WE HAVE A FANTASTIC POSTER
SESSION SO LET'S SUPPORT OUR
TRAINEES.
THERE WERE 68 POSTERS.
WE HAD A GREAT TIME REVIEWING
THE ABSTRACTS.
SO AFTER THIS YOU CAN TAKE A
SHORT I THINK I MADE UP SOME
TIME SO A LITTLE BIT BIO BREAK
AND THEN LET'S HEAD UPSTAIRS.
THE POSTER SESSIONS ARE DIVIDE
TO TWO SECTIONS.
THEY'RE UNTIL 4:00 IS GROUP A
AND FROM 4:00 TO 4:45 IS GROUP B
AND THEN 15 MINUTES TO BREAK
DOWN THE POSTERS.
THERE'S ALSO INCLUDE A DATA
COORDINATING CENTER DCC
SPONSORED HAPPY HOUR AND THAT IS
AT THE HYATT.
WHOEVER IS ATTENDING THAT,
PLEASE ASK FOR -- YOU MAY HAVE
RECEIVED INSTRUCTIONS BUT YOU
CAN ASK AT THE TABLE.
SO WE CAN TAKE A FEW QUESTIONS
AND THEN I'LL GO TO THE POSTER
SESSION.
THANK YOU.
>> HI.
FROM UNIVERSITY NORTH CAROLINA.
EXCITED TO HANG OUT WITH YOU.
WE HAVE A QUESTION ON
RESEARCHERS OR BASIC SCIENTISTS
CREATE THE BEST POSSIBLE DATA
FOR REUSE FOR ANALYTIC.
FROM A TRAINING PERSPECTIVE,
WHAT KIND OF EMBEDDING OR CROSS
POLINATETION -- POLINATING CAN
WE DO?
>> IT'S EARLIER IN THE TIME
POINT.
THOUGH THE INCLUDE R25 DOESN'T
ALLOW UPPER GRADUATE THE R25
DOES DO THAT.
AS YOU SAID WE HAVE TO TRAIN
EARLIER AND THE COURSE
DEVELOPMENTS ARE GREAT TO CREATE
THE BIO INFORMATICS AND DATA
SCIENTISTS WE NEED FOR THE
PIPELINE.
>> I HAVE A QUESTION ABOUT THE
K99, R00 AWARD AND I HEARD YOU
CAN'T DO A CLINICAL TRIAL BUT IF
AN IRB IS ESTABLISHED YOU CAN
PLAY OFF IS THAT AND I FEEL IT
WOULD GIVE US OPPORTUNITIES FOR
GOOD IMPACTFUL RESEARCH 37 -- SO
I WAS CURIOUS ABOUT THAT.
>> IF THERE'S A CLINICAL TRIAL
YOU CAN BE ON THE PROTOCOL.
I THINK IT'S CLINICAL TRIAL NOT
ALLOWED.
>> THANK YOU.
>> ONE QUESTION ABOUT THE
EDUCATIONAL OPPORTUNITIES.
SO IS IT POSSIBLE TO STAY IN THE
SAME LAB?
ONE OF THE AWARDS SOUNDED LIKE
YOU STATED THE SAME LAB AND GOT
AN AWARD IN THE POSTDOC WITH THE
SAME MENTORS.
>> FROM A K01 I ENDED UP
INCREASING MY MENTORSHIP BUT
SAME PEOPLE AND STRUCTURE.
FOR THE K99 FOR EXAMPLE, I THINK
THERE IS AN ASSUMPTION YOU'RE
GOING TO CHANGE UNIVERSITIES BUT
FOR THE K01 YOU'RE ALLOWED TO
STAY FIVE YEARS.
>> LET ME SKRCORRECT THAT.
FOR THE R00 YOU HAVE TO BE SHOW
INDEPENDENCE AND SHOWING YOUR
R00 IS INDEPENDENT OF THE
POSTDOC IS CRITICAL.
THEY CAN'T BE IN THE SAME
INSTITUTION.
>> AND MAYBE A NAIVE QUESTION
WAS THE CSF ACCUMULATION RELATED
TO HYDRO CEPHAL IS?
>> NO AND THEY WERE FREE OF
THOSE SYSTEMS OR DIAGNOSES.
>> SO HYDROCEPHALUS IS NOT
PREVALENT?
>> OCCURS IN THE CLINICAL
POPULATIONS AT HIGHER RATES.
>> NOTE IN OUR SAMPLES.
>> I LIKE THAT YOU SAID OUR
SAMPLES BECAUSE THAT'S BIG IN
OUR RESEARCH.
>> THERE'S BEEN GREAT TALK ABOUT
THE DATA THAT'S GOING TO BE
COMING OUT IN THE NEXT COUPLE
YEARS AND HOW WE'RE ALL WORKING
TOGETHER TO CREATE THIS DATA.
I HAVE A QUESTION ABOUT FUTURE
FUNDING WITH TONS T DATA WE CAN
REUSE BECAUSE RIGHT NOW IT'S
MAKING DATA RELEVANT ON
PREVIOUSLY CREATED DATA.
DO YOU SEE THAT SHIFT EVERYTHING
TIME WITH THE LARGE DATABASES?
>> I DO THINK WE'LL HAVE MORE
USE OF THE ROV 01.
IT'S A SMALL BUDGET RIGHT NOW
ABOUT 50,000.
>> YOU CAN'T SUPPORT MULTIPLE
RESEARCHERS ON IT.
>> WE CAN PLAN FOR THE SPECIFIC
YEAR.
WE'RE HOPING TO GET CONTINUED
SUPPORT FROM CONGRESS FOR
INCLUDE BUT TO BE HONEST, WE
DON'T KNOW WHAT THE NEXT FISCAL
YEAR LOOKS LIKE OR MAYBE A FEW
YEARS DOWN THE ROAD.
>> BUT IF IT DOES CONTINUE WILL
THE FOCUS STAY ON ONE LAB OR BE
MORE DATA RE-ANALYSIS?
>> AS THE LANDSCAPE SHIFTS WE
HAVE THIS REPERTOIRE OF
MECHANISMS AND THERE'S PARENT
MECHANISMS AND ANYONE WHO WANTS
TO APPLY CAN STILL APPLY TO THE
PARENT MECHANISMS AND IF THEY
HAVE DOWN SYNDROME FOCUS WE'LL
BE ABLE TO PICK THAT UP IF WE
HAVE THE FUNDING TO SUPPORT IT.
>> SOUNDS GREAT.
>> GREAT QUESTION.
THANK YOU.
>> PARDON IF I GOT MY FACTS
WRONG, BUT HAVE THE TRAINING
AWARDS IN THE ONE-YEAR JULY 1
SUBMISSION DATE OR MULTIPLE
CYCLES TO SUBMIT FOR?
>> THE INCLUDE F99 IS ONE
RECEIPT DATE PER YEAR.
THE K99, F00 HAS ONE A YEAR AND
WANT IT SEE HOW MANY WE GET AND
THE PARENT HAS THREE RECEIPT
DATES BUT THERE IS NO PARENT
F99.
THERE'S ONE THROUGH THE BRAIN
INITIATIVE AND OTHER I.C. NIDDK
HAS THEIR OWN F99.
SO THERE IS NO NIH PARENT --
>> WOULD YOU SUGGEST FOR THE F99
TO PLAN TO SUBMIT TWO YEARS OUT
TO HAVE A SECOND CHANCE?
>> THE ELIGIBILITY STARTS FOR
LIKE YEAR THREE OF YOUR
GRADUATE -- THAT'S A GREAT
QUESTION.
CAN STILL COME IN IN THE FOURTH
YEAR.
YEAH.
>> I HAVE A FOLLOW-UP.
I HAVE 99K0 AND THAT CAN BE
WORKING ON DOWN SYNDROME WHICH
CASE F OR 0 --
>> BOTH.
>> CAN THEY WORK ON THE SAME LAB
OR MUST CHANGE THE LAB FOR
POSTDOC TRAINING?
>> THAT'S A GOOD QUESTION.
I THINK THEY HAVE TO CHANGE LAB.
THEY DON'T HAVE TO IDENTIFY THE
LAB BUT TALK ABOUT THE SCIENCE
THEY DO.
>> BUT ONCE THEY GET THE AWARD
THEY NEED TO SELECT THE LAB --
>> THEN THERE'S A TRANSITION
PACKAGE.
AS I SAID, SIMILAR TO THE K99, R
OO THEY HAVE TO ESTABLISH
THEY'RE NOT JUST THE SAME WORK
BUT SOMETHING DIFFERENT AND HOW
DOES IT IMPACT THEIR CAREER
TRAJECTORY AND NOT THEIR
INVESTIGATOR GETTING MORE PAPER
IN THE SAME FIELD.
IT'S A PHASED TRAINING AWARD.
IT HAS TO HAVE AN IMPACT ON
THEIR CAREER.
IF STAYING IN THE SAME LAB BUT
DOING MAYBE THEY ARE THE
RESEARCH AND AGENCDDING OR
COLLABORATING THE CKOMCO-MENTOR
MODEL ANDING THE SHOWING THE
NEXT FACE IS DIFFERENT FROM THE
GRADUATE PROJECT, THAT SHOULD
SUFFICE BUT FOR THE K00 THEY
DON'T HAVE TO IDENTIFY A LAB.
>> THANK YOU.
>> IF THERE ARE NO MORE
QUESTIONS -- ONE MORE LAST
QUESTION.
>> SORRY.
THERE'S BEEN TRAINING
OPPORTUNITIES.
DOES THE INCLUDE PROGRAM
CONSIDER TO SET UP SOME SPECIAL
MECHANISM FOR TRACKING
ESTABLISHED RESEARCHERS FROM
OTHER FIELD TO THE KWLUD?
-- INCLUDE.
>> NO.
WE'RE ALREADY DOING THAT.
A LOT OF THE R MECHANISMS
ESPECIALLY THE R01s, TR01s ARE
SET UP WITH COLLABORATIONS AND
ALREADY HAVE INVESTIGATORS
ALREADY NOT STUDYING DOWN
SYNDROME AND DIDN'T HAVE A FOCUS
BUT HAVE BEEN APPLYING FOR R01s
JOINTLY WITH OTHER
INVESTIGATORS.
THE INCLUDE WEBSITE HAS ALL
THOSE MECHANISMS BUT IF INCLUDE
DOESN'T HAVE THE MECHANISM
PEOPLE CAN APPLY IT TO R01 BUT
HAS TO HAVE SOME FOCUS ON DOWN
SYNDROME TO BE ELIGIBLE FOR
FUNDING.
THANK YOU EVERYONE.
I THINK WE CAN CLOSE AND LET'S 6729 05:16:57,531 SUPPORT OUR POSTERS.