>>WELCOME TO NIH RESEARCH FESTIVAL.
THE FIRST SUCH FESTIVAL
HELD SINCE 2018.
I'M LENA SHORE THE DEPUTY
DIRECTOR FOR IN TRA MURAL
RESEARCH AND IT TRULY
AN HONOR AND PRIVILEGE TO
OPEN THIS YEAR'S FESTIVAL.
I WANT TO FIRST THANK ALL
OF YOU WHO HAVE COME
IN-PERSON.
YOU INTREPID SOULS, TO
JOIN US FOR THIS FESTIVAL.
AND THANK ALL OF THOSE WHO
ARE JOINING US ON VIDEO
CAST.
MUCH OF THIS FESTIVAL WILL
BE AVAILABLE ON VIDEO CAST
AS WELL BECAUSE WE WANT TO
REACH NIHERS FAR AND WIDE.
SO BEFORE I TELL YOU A
LITTLE BIT ABOUT WHAT
EXCITEMENT IS IN STORE
OVER THE NEXT SEVERAL
DAYS, I WANT TO THANK
CHRIS WONJACK, DIANA GOMEZ
AND SUSAN JULIE ANNIE FOR
ALL OF THEIR INCREDIBLE
WORK IN PUTTING THIS
FESTIVAL TOGETHER.
AND YOU WILL SEE, AS IT
UNFOLDS OVER THE NEXT
SEVERAL DAYS, REALLY ALL
OF THE HARD WORK THAT THEY
PUT INTO MAKING THIS
HAPPEN.
THE FIRST FESTIVAL,
ALTHOUGH IT WAS CALLED
RESEARCH DAY, REALLY
OCCURRED IN 1986.
AND THEN 1987 WAS REPLACED
BY A VERY IMPORTANT EVENT,
THE CENTENNIAL OF NIH.
FROM 1988 UNTIL 2019, THE
RESEARCH FESTIVAL OCCURRED
EVERY SINGLE YEAR ON THE
NIH CAMPUS.
SO WE ARE REALLY PART OF
AN INCREDIBLE HISTORY,
INCLUDING THE REEMERGENCE
OF THAT FESTIVAL AFTER
THREE YEARS DUE TO A
CERTAIN VIRUS THAT SHALL
BE UNNAMED.
SO I WANT TO LET YOU KNOW,
THIS FESTIVAL, AS IT'S
CONFIGURED REPRESENTS
EVERY CORNER OF ALL OF THE
NIH CAMPUSES.
YOU WILL SEE THE WORK OF
SCIENTISTS AT EVERY LEVEL
OF EXPERTISE FROM EVERY
AREA OF BIOMEDICAL
SCIENCE.
YOU WILL HAVE THE
OPPORTUNITY, AND I
CERTAINLY HOPE YOU TAKE
ADVANTAGE OF IT, TO
NETWORK WITH YOUR
COLLEAGUES.
TO ASK QUESTIONS, TO MAKE
SUGGESTIONS AND GENERALLY
JUST TO SCHMOOZE WITH
OTHER PEOPLE INTERESTED IN
BIOMEDICAL SCIENCE AND ITS
APPLICATION TO THE HEALING
AND WELL-BEING OF THE
PEOPLE EVERYWHERE.
I THINK THAT'S WHAT MAKES
THIS THE MOST EXCITING.
THE FACT IT ALLOWS
INTERACTION AMONG PEOPLE
THAT MIGHT NOT SEE EACH
OTHER EVERYDAY.
THE FACT IT ALLOWS JUNIOR
AND SENIOR MEMBERS OF OUR
COMMUNITY AND EVERYTHING
IN BETWEEN TO THINK
TOGETHER, TO TALK
TOGETHER, TO HAVE FOOD
TOGETHER, REALLY TO
SOCIALIZE AROUND SCIENCE
AND ITS CAP PRECIPITATION
TO THE HUMAN CONDITION.
IT ALSO ALLOWS VENDORS THE
PRODUCTS AND INFORMATION
AND ADVOCACY OPPORTUNITIES
TO BE ON OUR CAMPUS AND
INTERACT WITH US.
AND I THINK AS A PUBLIC
SERVICE ORGANIZATION NIH
IS NOT ONLY OBLIGATED BUT
HONORED TO WELCOME THEM TO
OUR CAMPUS AND TO INTERACT
WITH THEM TO HAVE A
DIALOGUE WITH THESE
INDIVIDUALS SO I DON'T
WANT TO DELAY OUR FIRST
EVENT ANYMORE.
I WOULD LIKE THE TURN THE
STAGE OVER TO
PARINAZ FATHI AND
Dr. TOKUNBOR LAWAL.
I LOOK FORWARD TO TALKING
WITH YOU AS THE NEXT
SEVERAL DAYS EVOLVE.
[APPLAUSE]
>> Parinaz Fathi: THANK
YOU
>> Tokunbor Lawal: I'M
NOT INDEPENDENT RESEARCH
SCHOLAR AT THE NATIONAL
INSTITUTE OF RESEARCH
SCHOLAR AND MY CH
CO-CHAIR.
>> Parinaz Fathi: I'M AN
INDEPENDENT RESEARCH
SCHOLAR AT NIBIB.
>> Tokunbor Lawal: JUST
BECAUSE A SIGNIFICANT WAY
INTO THE PRESENTATIONS,
IRS HAS A NICE RING TO IT.
BUT WE'RE SIMPLY
NON-TENURE PRINCIPAL
INVESTIGATORS.
WE'VE BEEN SELECTED
BECAUSE WE ARE READY TO
PERFORM AND CONDUCT
INDEPENDENT RESEARCH AND
WE'RE ALSO COMMITTED TO A
DIVERSE BIOMEDICAL
WORKFORCE.
HAVING SAID ALL OF THAT,
YOU WILL SEE FROM YOUR
AGENDA THAT OUR SESSION IS
GOING TO OVERLAP SLIGHTLY
WITH THE FIRST POST
SESSION BUT THAT'S OKAY.
WE ARE GOING TO TRY TO
MOVE THIS AS QUICKLY AS WE
CAN AND GET YOU THROUGH
THOSE POSTER SESSIONS OF
THE LET ME INTRODUCE OUR
FIRST PRESENTER.
Dr. ANDREW KESNER.
HE IS PART OF THE 2021 IRS
COHORTS.
HE HAS A LAN WITH NIAAA.
HIS LAB IS THE UNION ET ON
MOTIVATION AND AROUSAL.
HE ALSO GRADUATED FROM
JOHNS HOPKINS UNIVERSITY
AND HE WENT THROUGH THE
GPP PROGRAM, THE GRADUATE
PARTNERSHIPS PROGRAM HERE
AT NIH AND HE DID HIS
THESIS WORK THROUGH NIAID.
WITHOUT FURTHER ADIEU,
Dr. KESNER, YOU HAVE THE
FLOOR.
[APPLAUSE]
OF.
>>OKAY, HELLO EVERYONE,
YEAH, THANK YOU.
IT'S ON AUTO PILOT.
THERE IT IS.
ALL RIGHT, GREAT.
HELLO, EVERYONE.
I WANT TO ECHO Dr.
SHORE'S THANKS TO YOU ALL
FOR BEING HERE.
I FEEL LIKE THE PHOENIX
RISING OUT OF THE ASHES OF
THE PRIOR NIH RESEARCH
FESTIVALS.
SO THANK YOU ALL FOR
JOINING ME.
YES, SO I'M EXCITED TO
INTRODUCE YOU TO THE WORK
WE'RE DOING IN MY UNIT.
THE UNIT ON MOTIVATION AND
AROUSAL AND I'M GOING TO
JUMP RIGHT INTO IT.
SO THE MAIN LONG-TERM
MISSION OF MY UNIT IS TO
UNDERSTAND HOW BRAIN
SYSTEMS CONTROL MOTIVATED
BEHAVIORS AND SLEEP OR
AROUSAL PROCESSES
INTERACTED DRIVE MALL
ADAPTED BEHAVIOR AND TO
JUST ORIENT THIS KIND OF
FROM A BIRD'S EYE VIEW
THIS IS IMPORTANT BECAUSE
MOST IF NOT ALL
PSYCHIATRIC OR MENTAL
HEALTH DISORDERS HAVE
SLEEP-WAKE CO-MORBIDITY SO
IF YOU GO INTO PUBMed
AND YOU SEARCH FOR ONE OF
THESE TYPE OF DISORDERS,
AND SLEEP, YOU WILL FIND
SOME HITS THAT ARE LOOKING
AT THAT RELATIONSHIP OR
NOTICING THAT
RELATIONSHIP.
AND ONE THING THAT I THINK
IS PARTICULARLY
INTERESTING AND SOMETHING
THAT WE'RE KIND OF SETTING
THE GROUPED WORK TO BE
ABLE TO DO IS TRY TO
ANSWER THIS CHICKEN AND
EGG PHENOMENON WHERE WE'RE
NOT SURE WHETHER A SLEEP
DISORDER, HAVING A SLEEP
DISORDER MIGHT PRE DISPOSE
YOU FOR A MENTAL HEALTH
HEALTH DISORDER OR VICE
VERSA OR WHETHER MENTAL
HEALTH MANIFEST AS A
SLEEP-WAKE PHENOMENON.
SO I'M A BEHAVIORAL
NEUROSCIENTIST AND MY
BACKGROUND AND MAIN
INTEREST OF THOSE TYPE OF
DISORDERS IS SUBSTANCE USE
DISORDER.
AND IT TURNS OUT THAT
SLEEP DISTURBANCE IS
PARTICULARLY COMMON IN
SUBSTANCE USE DISORDER ALL
MISUSE SUBSTANCES PRETTY
MUCH AFFECT SLEEP IN SOME
WAY AND EITHER OUT WITH
THEM DURING WITHDRAWAL,
THEY OFTEN REPORT HAVING
SLEEP DISRUPTION AND IT'S
ONE OF THE PRIMARY CAUSES
OF RELAPSE.
PEOPLE SAY I JUST NEED THE
DRUG TO SLEEP.
WHEN I STOP TAKING IT I
CAN'T FALL ASLEEP AND I'M
UP ALL NEED SO YEAH, IT'S
A PARTICULARLY IMPORTANT
RELATIONSHIP WHEN LOOKING
IN THE LENS OF SUBSTANCE
USE DISORDER AND SIMILARLY
IT MAKES SENSE BECAUSE IF
I PUT UP HERE AN IMAGE
FROM THE SEMINAL REVIEW ON
REGIONS INVOLVED IN SLEEP,
THOSE OF YOU WHO STUDIED
MOTIVATED BEHAVIORS OR
SUBSTANCE USE DISORDERS
WILL LIKELY SEE MANY OF
THE REGIONS YOU ARE
INTERESTED IN STUDYING.
SO THE BRAIN IS ORGANIZED
FOR THIS OVERLAP TO
MANIFEST.
THIS SAME REGIONS THAT ARE
IMPORTANT FOR MOTIVATION
AND REWARD SEEKING, THE
THINGS THAT BECOME HIGH
JACKED DURING SUBSTANCE
USE DISORDERS ARE ALSO
ONCE THAT PLAY AN
IMPORTANT ROLE IN
SLEEP-WAKE.
LIKEWISE, SLEEP DISRUPTION
ITSELF, BEYOND THE CONTEXT
OF SUBSTANCE USE DISORDER
CAN CAUSE CHANGES TO THESE
REGIONS THAT ARE INVOLVED
IN SUBSTANCE USE DISORDERS
SO AGAIN THERE'S THIS
RELATIONSHIP AT THE
NEUROPHYSIOLOGICAL LEVEL
THAT MAKE THIS INTERACTION
BETWEEN SLEEP AROUSAL AND
MOTIVATED BEHAVIORS MAKE
SENSE.
SO, OUR APPROACH IS TO
LOOK AT THIS FROM
ASSISTANCE NEUROSCIENCE
LEVEL.
WE ARE INTERESTED IN
LOOKING AT ALL THINGS FROM
DOWN FROM THE SYNAPSE
THROUGH POPULATION OF
NEURON ACTIVITY, HOW THOSE
DIFFERENT BRAIN REGIONS
ARE TALKING TO ONE ANOTHER
ALL THE WAY THROUGH A
WAKE, BEHAVING OR SLEEPING
ANIMALS, IN MY CASE.
SO THAT IS A PRETTY BIG,
TALL ORDER SO TO SPEAK.
WE NEED TO THINK OF A
PLACE TO START.
THE REGION IS LOOK AT IS
IS THIS REGION CALLED THE
MEDIAL SEPTUM.
HOPEFULLY YOU WILL THINK
THIS IS AN INTERESTING
PLACE TO STUDY DON'T WE
KNOW THIS REGION IS
INVOLVED IN BOTH SLEEP AND
GOAL DIRECTED BEHAVIORS OR
MOTIVATED BEHAVIORS.
ACTUALLY BACK IN THE
1950s, WHEN JAMES OLDS
AND PETER MILNER WERE
DOING THESE SEMINOLE
STUDIES YOU REMEMBER FROM
PSYCHE 101 WHERE THEY PUT
ELECTRICAL STIMULATION OF
THOSE PARTS OF THE BRAIN
IN RAT AND IF THE RAT SIT
THERE AND HIT THE LEVER
OVER AND OVER AGAIN THE
REGION WAS REINVOLVED IN
REWARD OR MOTIVATED BEHAVE
YEARS IN SOME WAY.
SO THE SEPTUM IS THE FIRST
REGION THEY DISCOVERED.
IT FELL TO THE WAY SIDE
AMONGST THE INTERESTING
THINGS THEY WERE
DISCOVERING USING THIS
TECHNIQUE.
UNTIL ABOUT OVER HALF
DECADE LATER, I WAS
INTERESTED IN THIS REGION
IN MY PH.D WORK AND I'LL
TELL YOU THAT IN A SECOND.
IT'S INVOLVED IN REWARD OR
MOTIVATED BEHAVIORS AND
ALSO IN SLEEP.
WHEN YOU LESION THIS BRAIN
REGION IT EFFECTS
SLEEP-WAKE PROCESSES.
WE KNOW IT'S IMPORTANT FOR
DRIVING THESE TYPE OF OF
BRAIN RHYTHMS THAT YOU SEE
DURING DIFFERENT STAGES OF
SLEEP.
SO HERE IS WHERE THE
MEDIAL SEPTUM IS.
IT'S IN THE MIDDLE OF THE
BRAIN.
YOU WILL SEE IMAGES LATER
AND THIS IS WHERE YOU ARE
TUNING INTO.
THIS REGION REGION IS A
HETEROGENEOUS OF NEURONS
AND THEY RELEASE GUETTA
AMEEN, GAB A AND IT HAS A
VERY DIFFUSE DETECTIVE TEE
THROUGHOUT THE BRAIN MANY
OF IT'S AN INTEGRATED TYPE
REGION MANY OF YOU CAN SEE
BRAIN REGIONS THAT IT'S
TALKING TO OR THAT TALK TO
IT THAT ARE INVOLVED IN A
LOT OF THE THINGS THAT
WE'RE INTERESTED IN.
SO I BECAME INTERESTED IN
THIS REGION BY DOING
SIMILAR TECHNIQUES TO WHAT
I DESCRIBED WITH
ELECTRICAL STIMULATION.
I WAS USING A TECHNIQUE
CALLED ON TOE GENETICS
WHERE I PUT AN EYE ON
CHANNEL AND WHEN YOU SHINE
A WAVE LENGTH OF LIGHT ON
THAT ION CHANNEL A NERVE
LINK WITH FIRE SO WE CAN
STIMULATE DIFFERENT
POPULATIONS OF NEURONS
USING THIS TECHNIQUE.
SO ALL THE NEURONS IN THE
MEDIAL SEPTUM TURNED THE
NEURONS ON I FOUND QUICKLY
THEY LEARNED TO LEVER
PRESS ACTIVELY SO THIS IS
CALLED ACQUISITION OF
SELF-STIMULATION BEHAVIOR
AND IT WAS ONLY
RECAPITULATED WHEN I PUT
IT ON GLUTE A MEAN IN THE
MEDICINE Y'ALL SEPTUM AND
YOU CAN SEE HERE THAT
MATCHES THAT LINE OF ALL
THE DIFFERENT NEURONS.
SO THIS CONCLUDE US IN
THAT TURNING OF THESE
NEURONS IS REWARDING.
WHAT ASPECT OF NATURAL
REWARD-SEEKING BEHAVIOR
MIGHT THESE NEURONS BE
INVOLVED IN.
THIS IS AN IMPORTANT FIRST
QUESTION IF WE WANT TO
TALK ABOUT THE
RELATIONSHIP BETWEEN
SUBSTANCE USE DISORDER AND
SLEEP BECAUSE WE NEED TO
MOW WHAT THESE NEURONS ARE
DOING NORMALLY BEFORE WE
CAN ASK QUESTIONS ABOUT
HOW THEY MIGHT BE HIGH
JACKED BY DIFFERENT
SUBSTANCES OF ABUSE.
YOU MIGHT THINK ABOUT THE
OTHER SIDE OF THE
QUESTION.
WHAT ABOUT THE ROLE IN
SLEEP.
IT TURNS OUT I DON'T HAVE
TO DO THAT WORK BECAUSE A
GROUP ABOUT A YEAR AGO,
PUBLISHED THAT THESE
POPULATION ARE INVOLVED IN
SLEEP AND THEY WENT
THROUGH A VERY CAREFUL
CHARACTERIZATION OF ROLE
OF THESE NEURONS IN SLEEP
AND CIRCUITRY INVOLVED.
SO WE'RE STICKING WITH
THIS FIRST QUESTION FOR
NOW.
THE WAY THAT WE ARE GOING
ABOUT DOING THIS IS TWO
PRONGED.
WE'RE GOING TO BOTH -- WE
ARE MODULATING THIS
POPULATION OF NEURONS AND
I'LL TELL YOU ABOUT THAT
AND WE'RE ALSO RECORDING
FROM THIS POPULATION OF
NEURONS.
THE IDEA HERE JUST TO GET
AN OVERVIEW OF WHAT TYPE
OF REWARD-SEEKING
BEHAVIORS THESE NEURONS
ARE INVOLVED IN.
FIRST I'LL SHOW YOU
RECORDING STUDIES.
WE'RE USING A TECHNIQUE
CALLED FIBER FOE TOM TREE
IN AWAKE BEHAVING ANIMALS.
WE USE A VIRUS TO EXPRESS
CALCIUM SENTER CALLED G
CAMP AND THIS SENSOR LIVES
IN THE NEURONS AND WHEN A
NEURON FIRES THERE'S AN
INFLUX OF CALCIUM AND
CAUSES THE FLUORESCENT
SIGNAL GO.
WE RECORD THE DYNAMICS AND
YOU CAN SEE ACROSS A 30
MINUTE SESSION THESE
TRANCE' ENTERS IN THIS
GREEN CHANNEL HERE.
NOTHING IN THIS RED
CONTROL CHARGE.
SO THIS IS TELLING US WHAT
WE'RE SEEING IS THE
POPULATION ACTIVITY OF
THESE MEDICINE Y'ALL
SEPTAL SO WE PUT THE MICE
IN A CHARM TER AND ASKED
THEM TO PRESS DIFFERENT
LEVERS.
WE CAN LOOK AT HOW THE
ACTIVITY OF THESE NEURONS
RELATE TO THE DIFFERENT
BEHAVIORS WE'RE LOCKING
AT.
I'LL GIVE YOU REAL
HIGHLIGHTS.
I DON'T HAVE MUCH TIME.
THESE NEURONS RESPOND TO
DIFFERENT TYPES OF SAME
BEHAVIOR.
LEVER PRESSING.
THE MOUSE CAN PRESS THE
LEVER AND EARN A REWARD
AND PRESS THIS ACTIVE
LEVER AND NOT EARN A
REWARD AND PRESS AN
INACTIVE LEVER.
THE MAIN PICTURE HERE IS
THESE NEURONS WHEN WE
ALIGN THE CALCIUM SIGNAL
TO THE LEVER PRESS
BEHAVIOR THEY LOOK
DIFFERENT.
LEVER PRESS, THAT'S IT.
THE NEURONS ARE RESPONDING
DIFFERENTLY BASED ON THE
VIOLENCE OF THAT BEHAVIOR.
WHEN WE LOOK AT PICKING
BEHAVIOR.
WHEN THE ANIMAL LOOKS AT
THIS PORE, AND WE KNOW
THERE'S REWARD THERE.
AND IT'S BLUE-LINE VERSUS
A LICK WHERE WE KNOW
THERE'S NO SUCROSE THERE.
IT'S IN BETWEEN REWARDED
SESSIONS.
THE POPULATION ACTIVITY
LOOKS DIFFERENT.
SO JUST BASIC BIRD'S EYE
VIEW OF THESE.
THESE NEURONS ARE
RESPONDING DIFFERENT TO
THE SAME TYPE OF BEHAVIOR
BASED WHETHER IT'S
ASSOCIATED WITH THE REWARD
OR NOT.
SO THINGS ARE BECOMING A
LITTLE CLEARER.
WE WENT ON AND WE
MODULATED THE POPULATION
OF NEURONS USING A
TECHNIQUE CALLED CHEMO
GENETICS WHICH IS WHERE WE
AGAIN USE VIRUSES TO
EXPRESS NOW THESE
DIFFERENT G PROTEIN COUPLE
RECEPTORS WHEN WE INJECT A
DRUG THAT DOES NOTHING
OTHERWISE INTO THE ANIMAL,
IT WILL ACTUATE THESE
PROTEIN COUPLE RECEPTORS
THAT NOW LIVE ON THE
SPECIFIC POPULATION WE'RE
STUDYING AND WE CAN USE GQ
DRUGS, THIS IS DESIGNER
RECEPTORS EXCLUSIVELY
ACTIVATED BY DESIGNER
DRUGS.
WHEN WE USE GQ DRUGS THAT
CAUSE THE NEURON ACTIVITY
TO INCREASE AND WE USE GI
DREADS IT INHIBITS THE
NEURONS.
WE KNOW THIS IS WORKING.
WE SEE VERY NICE TIGHT
SPACIAL ASSOCIATION OF OUR
DREADS WITH THE MEDIAL
ACCEPT SSTUM AND WHEN
HE HAVE A NARCKER FOR
NEWER OWNAL ACTIVITY
BEFORE SACRIFICING THE
ANIMAL.
WE SACRIFICE THE ANIMAL
THEN WE STAIN FOR THAT.
IT TELLS US WE HAVE STRONG
NORMAL ACTIVITY AND
MEDICINE Y'ALL GLUTEAMATE
NEURONS WITH THE GQ MICE
AND LESS WITH THE GI MICE
AND IN THE MIDDLE WITH THE
CONTROL GROUP.
WE THINK IN VIVO THIS
MANIPULATION IS WORKING.
WHEN WE PUT THE ANIMALS
THIS THIS CHEM BETTER AND
REWARD SINGHING BEHAVIOR,
WHAT WE SEE IS THAT WHEN
THE ANIMALS KNOW THE TASK
REALLY WELL, WE DON'T SEE
MUCH EFFECT OF THIS CHEMO
GENETIC MANIPULATION BUT
WHEN WE REVERSE WHICH
DELIVER DELIVERS THE
REWARD AND WHICH DOES
NOTHING, WE SEE THAT NICE
OF GQ THEY LEARN THIS
REVERSAL REALLY QUICKLY
AND THIS IS REALLY FAST
FOR LEARNING THIS TYPE OF
BEHAVIOR.
THEY LEARN IT WITHIN THE
FIRST DAY.
THEY'RE EARNING THE SAME A
LOT OF REWARDS THAT THEY
HAVE BEFORE.
IS HE WE USE A DIFFERENT
PARADIGM.
THEY LISTEN TO DIFFERENT
CUES AND WE DO THE SAME
THING AND WE WE CHANGE THE
RULES, AUDITORY QUEUE DOES
NOTHING AND A LIGHT
BLINGING TELLS US THERE'S
A WARD AND AGAIN THIS
BLUE-LINE ARE LEARNING
THIS FASTER OF THE THEY'RE
DISCRIMINATING BETWEEN
THESE NEW RULES MUCH
QUICKER THAN THE OTHER
GROUPS SO NOW WORE GOING
FORWARD WHERE WE'RE START
TO GO STUDY THINGS LIKE
HOW OF THEY CONTROL
DOPAMINE BECAUSE WE KNOW
THAT THAT DOPAMINE IS
IMPORTANT FOR THE STRATEGY
SWITCHING BEHAVIOR.
WE ALSO KNOW THAT MEDIAL
AND NEURONS TALK TO
DOPAMINE NEURONS SO THEY
PROJECT TO THE AREA WHERE
THERE'S A LOT OF DOPAMINE
NEURONS AND WHEN WE
STIMULATE THOSE MEDIAL
SEPTAL TO THE MENTAL AREAS
WE SEE A LOT OF DOPAMINE
RELEASE LIKE WHAT I SHOWED
YOU BEFORE AND SO I'M JUST
GOING TO HIGHLIGHT THE
FIRST TID BIT OF ANALYSIS
WE HAVE ON THIS AND WE'RE
SEEING SOMETHING
INTERESTING, MICE WITH GQ,
THE MICE THAT DO BETTER AT
THESE REVERSAL TASKS THEY
HAVE AN INCREASE OF
DOPAMINE WHEN THEY GET
THIS REWARD ON THE FIRST
DAY OF THE REVERSAL AND SO
THIS IS TELLING US THESE
NEURONS ARE FACILITATING
THIS VERY CON ON CONTACT
ROLE OF REWARD PREDICTION
ERROR AND TO LET THESE
MICE LEARN THIS STRATEGY
SWITCHING MUCH QUICKER SO
SUMMARIZE, THEY RESPOND
DIFFERENTLY DEPENDING ON
THE BEHAVIOR AND THE
ENHANCEMENT OF THIS
ACTIVITY CAN INCREASE
STRATEGY SWITCHING.
IT CAN MAKE THEM BETTER AT
DOING THIS AND IT LOOKS TO
BE DUE TO THEIR EFFECT
OF -- SO THE NEXT THINGS
WE'LL LOOK AT DO THEY
ALTER THE ACTIVITIES
GETTING AT THE SUBSTANCE
USE DISORDER QUESTIONS I
WAS TELLING YOU ABOUT.
ARE THEY INVOLVED IN SLEEP
DISTURBANCE DURING DRUG
WITHDRAWAL AND CAN
ENHANCEMENT OF THESE GLUTE
MATE NEURONS HELP WITH
MAINTAINING ABSTINENCE AND
ABSTINENCE IS SORT OF A
STRATEGY SWITCHING TYPE
THING.
YOU WANT TO SWITCH YOUR SO
INFLUENCING THE ACTIVITY
OF THESE COULD BE SOME
SORT OF THERAPEUTIC
THERAPY FOR HELPING WITH
ACCIDENTS.
SO WE HAVE A COUPLE OTHER
PROJECTS THAT WE'RE
LOOKING AT IN MY UNIT.
THIS KINDS OF FOCUS ON
WHAT I JUST SHOWED YOU AND
WE'RE ALSO LOOKING AT THE
ROLES OF SLEEP AND AROUSAL
USING OTHER SORT OF
SIMILAR TECHNIQUES AND
ALSO WAYS TO GO ABOUT
THOSE QUESTIONS.
WE'RE PARTICULARLY
INTERESTED IN THC
WITHDRAWAL BECAUSE ALMOST
UNIVERSALLY PEOPLE REPORT
HAVING SLEEP DISRUPTION
AND WE'RE ALSO TRYING TO
UNDERSTAND IS THOSE THE
THINGS WE'RE DOING AND ONE
OF THE MAIN PROJECTS WE'RE
WORKING ON AND I WANT TO
THANK Dr. LEVEN GER FOR
BEING MY POSTDOC MENTOR
AND NOW MY TEN TORR AND I
WANT TO THANK STEPHANIE
AND NINA AND THEY JUST
MOVED ON AND THEY'RE IN
GREAT POST GRADUATE AND
MEGAN AND KAYLA HERE AND
THEY CAN TELL YOU MORE
ABOUT THE EXPERIMENTS THAT
I JUST TOLD YOU ABOUT SO
I'LL TAKE QUESTIONS IF
THERE'S ANY TIME OTHERWISE
THANK YOU VERY MUCH.
[APPLAUSE]
GREAT PRESENTATION, THANK
YOU, ANDREW.
WE HAVE TIME.
WE HAVE PEOPLE ON-LINE AS
WELL THAT MAY HAVE
QUESTIONS.
>>NO QUESTIONS ON-LINE.
PEOPLE CAN SUBMIT, OF
COURSE.
>>ABSOLUTELY.
IT'S UP TO PEOPLE HERE IN
PERSON.
WE REQUIRE ONE QUESTION
WHEN WE HAVE TIME FOR IT.
YOU CAN WALK UP TO ANY OF
THE MICROPHONES.
>>SO WITH YOUR DIFFERENT
DREADS, DO YOU OBSERVE ANY
OBVIOUS CHANGES IN THE
SLEEP CYCLE OR ACTIVITY
WITH THESE MICE THAT WITH
HINT YOU TOWARDS THE
ANSWERS TO SOME OF YOUR
FUTURE QUESTIONS?
>>YES, THAT'S A GREAT
QUESTION AND LIKE I SAID,
THERE WAS A GROUP THAT
KIND OF ALREADY DID THOSE
EXPERIMENTS SO THEY USED
THAT ON TOE GENETICS
TECHNIQUE TO STIMULATE
NEURONS IN THE SLEEP AND
THEY SEE THE APP MALL
WAKES UP AND YOU INHIBIT
THEM AND THEY GO INTO A
DEEPER STATE OF RECOMMEND
SLEEP SO WE KNOW THEY'RE
PLAYING A ROLE THAT WAY.
>>IS THAT WHY THEY ADAPT
FASTER BECAUSE THEY'RE
AWAKE LONGER AND ACTIVE
LONGER AND CAN HAVE MORE
PRACTICE WITH THESE
BEHAVIORS?
>>SO THAT'S AN
INTERESTING POINT.
THE THING THAT I DON'T
THINK THAT'S WHAT IS GOING
ON PER SE IS BECAUSE WE
SEE THEM FIGURE THERE'S A
REVERSAL TASK OUT BEFORE
THEY'VE HAD TIME TO GO TO
SLEEP SO THEY ONLY GET ONE
HOUR OF BEHAVIOR PER DAY
AND WE SEE IN THAT FIRST
SESSION WHEN WE CHANGE THE
RULES, THEY FIGURE IT OUT.
SO I DON'T THINK THEY'RE
NAPPING AND HAVING MEMORY
CONSOLIDATION WHEN THEY'RE
GETTING THEIR TASTY TREAT
THEY'RE JUST FIGURING OUT
A DIFFERENT WAY TO GET IT
FASTER THAN THE OTHER MICE
WHICH IS REALLY NEAT.
COOL.
>> Tokunbor Lawal: THANK
YOU.
[APPLAUSE]
OUR NEXT PRESENTER IS
Dr. CARRIE MAE LONG.
SHE'S WITH THE
PATHOGENESIS SECTION AT
NIAID AND SHE GRADUATED
FROM WEST VIRGINIA
UNIVERSITY.
AND I'M TAKING YOUR DEGREE
WAS IN MICRO PATHOGENESIS
AND WELCOME.
>>ALL RIGHT.
SOUND GOOD?
OKAY.
THANK YOU SO MUCH FOR
HAVING ME HERE.
I'M REALLY EXCITED TO
PRESENT SOME OF THE WORK
MY GROUP IS DOING.
I'M GOING TO TALK ABOUT
ALLERGIES AND I'LL TRY TO
KEEP IT AT A 30,000-FOOT
LEVEL BECAUSE I KNOW NOT
EVERYONE CARES ABOUT
BACTERIA AND IMMUNOLOGY
BUT WE TRY TO COME UP WITH
BETTER COUNTERMEASURES FOR
BACTERIAL DISEASE LIKE KEY
FEVER.
SO BECAUSE I'M NOT FROM
INCAMPUS I WANT TO GIVE
YOU GUYS AN OVERVIEW OF
WHO I AM.
THAT'S ME.
I WORK IN THE HIGH
CONTAINMENT LAB.
BECAUSE WE WORK ON NASTY
BACTERIAL PATHOGENS AND I
WORK AT ROCKY MOUNTAIN
LABS SO WE'RE A SATELLITE
BRIDGE.
I'M IN THE LAB OF
BACTERIOLOGY AND THERE'S
ALSO NEWER LOGIC INFECTION
AND IMMUNITY AND THE LAB
OF VIROLOGY.
THIS IS THE BUILDING MY
OFFICE IS IN.
IT'S ALL OF OUR LEVEL TWO
LABS MANY OF THIS IS OUR
LEVEL 3 FACILITY AND THIS
IS OUR INTEGRATED RESEARCH
FACILITY WITH BSL4 AND WE
HAVE RTV SUPPORT SER SISS
ON CAMPUS THAT MANY OF YOU
IN NIAID MAY HAVE USED.
I'LL JUMP INTO BACKGROUND
ABOUT THE PATHOGEN WE WILL
FOCUS ON TODAY.
IT'S CALLED COX ELLIE A
BURNETTII IT'S KNOWN FOR
ITS ENVIRONMENTAL
RESISTANCE SO IF YOU HEARD
OF A SORE LIKE AN TREX, IT
CAN DO SOMETHING SIMILAR
AND THIS IS A LIFE CYCLE
AND THESE ARE LARGE AND
SMALL RELEVANT VARIANTS
AND THE SMALL YOU FIND OUT
IN THE SOIL THAT ARE VERY
INFECTIOUS.
ANOTHER PERMUTATION WAS
WORKING IS IT IS
CONSIDERED A SELECT AGENT.
THAT'S A PROGRAM RUN BY
THE CDC AND WE HAVE TO
WORK WITH A LOT OF
REGULATION AND UNDERSTAND
CONTAINMENT.
SO WE CARE ABOUT COCIELLA
AND PEOPLE GET EXPOSES OF
INHALATION FROM LIVESTOCK.
TICKS MAY HAVE A ROLE IN
NATURAL LIFE CYCLE BUT WE
DON'T UNDERSTAND THAT AS
WELL.
FURTHER THERE ARE OTHER
FORMS OF EXPOSURE THAT ARE
NOT AS PREVALENT.
SUCH AS INGESTION OF
CONTAMINATED MILK, BIO
TERROR POTENTIAL AND
LABORATORY REQUIRED
INFECTIONS BUT ON A
DAY-TO-DAY BASIS THE
PEOPLE THAT ARE MOST
LIKELY TO GET EXPOSED ARE
THOSE WHO WORK AROUND THE
LIVESTOCK.
PEOPLE WHO WORK IN VETS OR
EVEN RANCHERS.
SO INTERESTINGLY ABOUT 60%
OF PEOPLE EXPOSED ARE
THOUGHT TO REMAIN
ASYMPTOMATIC AND WE HAVE
NO IDEA WHY.
FOR THE OTHER 40% THEY'RE
GOING TO EXPERIENCE A
BROAD SPECTRUM OF CLINICAL
DISEASE THAT WE CALL Q
FEVER.
AND SO A Q FEVER IS
TREATABLE BY ANTIBIOTICS
OR SELF-LIMITING BUT THINK
OF IT AS A SEVERE FLU LIKE
ILLNESS WITH SOMETIMES
OTHER ORGANS BEING
INVOLVED.
ALL RIGHT.
NOW THERE'S ANOTHER FORM
OF THE DISEASE THAT IS
MUCH MORE RECOWS GRANT AND
MUCH MORE SERIOUS IN TERMS
OF MORTALITY.
IT'S CALLED CHRONIC Q
FEVER.
AND USUALLY THIS INVOLVE
MANIFESTATIONS LIKE
CHRONIC PNEUMONIA,
HEPATITIS, VAAS CUE LIGHT
US AND NOW A NEWLY
ASSOCIATED SYNDROME THAT'S
BEEN RECENTLY DESCRIBED IS
THE Q FEVER FATIGUE
SYNDROME AND YOU THINK
THAT HAVE IS BEING SIMILAR
TO LONG COVID EX SIMILAR
IN A SENSE WE DON'T REALLY
UNDERSTAND IT'S
PATHOGENESIS AND
MECHANISTICALLY.
AND THERE'S A VACCINE YOU
CAN GET THAT PREVENTS ALL
OF THESE MANIFESTATIONS
IT'S CALLED Q VAX AND IT'S
COXIELL THAT'S BEEN KILLED
MANY OF IT'S A GREAT
VACCINE IN TERMS OF
INDUCING PROTECTION,
PRETTY MUCH AFTER ONE
INTEXTURE PROJECTED IN
LIFE SO IT'S ONE OF THE
BEST VACCINES OUT THERE
BUT THERE ARE A FEW
PROBLEMS WITH IT AND WE'LL
GET INTO THAT IN A FEW
SLIDES.
NOT TO GO TOO FAR IN THE
WEEDS BUT I WANT TO TELL
YOU WHAT WE WORK WITH A
LOT SO THIS IS A MAP OF
THE AREA OF MONTANA THAT I
LIVE IN.
HAMILTON IS WHERE OUR
LABORATORY IS.
IF YOU DRIVE AN HOUR AND A
HALF NORTHWEST OF OUR LAB,
THERE'S A RURAL AREA
CALLED THE NINE MILE CREEK
BASINS AND THIS IS WHAT IT
LOOKS LIKE.
SO BACK IN THE 1930s,
SCIENTISTS WERE DOING TICK
SURVEYS LOOKING FOR THE
CAUSE OF AGENT ON ROCKY
MOUNTAIN FEVER BUT THEY
FOUND A ODD FEVER CAUSING
AGENT AND TURNS OUT IT WAS
COXIELLA BURNETTII SO WE
WORKED WITH THE TRAIN AND
THIS IS OUR LABORATORY
WORK HORSE.
THEY'RE THREE DIFFERENT
TYPES OF THE STRAIN.
SO IF YOU KNOW ANYTHING
ABOUT BACTERIA YOU KNOW
THAT GRAND NEGATIVE HAVE
POLY SACK RIDE ON THE
OUTSIDE OF THEIR MEMBRANE.
THE LPS IS UNIQUE IN THE
SENSE THAT WE ISOLATE IT
WITH THIS LONG FOLDING LPS
WHEN WE PASSAGE IS INVETO
THE LPS GETS SHORTER AND
SHORTER SO THESE FORMS AND
SO THE IMPORTANCE OF THIS
IS THAT YOU NEED LONG LPS
FOR VUL VIRULENTS AND FULL
VACCINE PROTECTION.
THIS IS KIND OF AN
OVERVIEW OF WHAT MY GROUP
DOES OF THE WE USE ALL OF
THESE DIFFERENT
TECHNIQUES.
WE'RE HEAVY ON ANIMAL
MODELING AND GENETICS AND
IMMUNOLOGY AND WE WANT TO
COME UP WITH BETTER
COUNTERMEASURES FOR Q
FEVER.
THINK BACK TO WHERE I TOLD
YOU THERE WAS A VACCINE
THAT'S GOOD CALLED Q VAX.
IT'S GOOD IN TERMS OF
PROTECTION BUT IT HAS A
SEVERE DRAWBACK IT INDUCES
SEVERE ALLERGIC RESPONSES
AND THIS HAPPENS IN PEOPLE
WHO HAVE BEEN EXPOSED O AT
SOME POINT OR HAVE ALREADY
BEEN VACCINATED.
AND SO THE ONLY PLACE YOU
CAN GET THIS VACCINE IS
AUSTRALIA.
SO LET'S YOU FLY TO USE
TRAIL Y YOU HAVE TO DO PRE
SCREENING TEST TO GET
VACCINATED INCLUDING
PATIENT HISTORY, TESTING,
A SKIN TEST THAT TAKES A
WEEK.
AND UNFORTUNATELY IF YOU
ARE NEGATIVE FOR AWFUL
THESE YOU CAN STILL HAVE A
SEVERE REACTION TO THE
VACCINATION.
SO THE SKIN TEST IS VERY
SIMILAR TO A T.B. SKIN
TEST.
HERE IS A POSITIVE
REACTION.
YOU CAN IMAGINE IF THIS
PERSON WAS GIVEN THE FULL
DOSE OF VACCINE THEY WOULD
HAVE A REAL PROBLEM.
THAT'S WHAT HAPPENS HERE
TOE THIS EMPLOYEE FROM
ROCKY MOUNTAIN LAB IN THE
1960s.
SO Q VAX WAS DEVELOPED AT
RML AND THIS EMPLOYEE WAS
VACCINATED AND THEY HAD TO
GET REMOVED A CYST FROM
THEIR MUSCLE ALONG WITH
PART OF THEIR TRY ACCEPT
MUSCLE.
THIS IS A COMPLETELY BAD
RESPONSE THAT PRE INCLUDES
WIDESPREAD TO THE POINT OF
THE VACCINE.
AND SO HOW ARE WE COMING
UP WITH A BETTER VACCINE,
RIGHT?
WELL WE STARTED TO MODEL
THIS POST VACCINATION
ALLERGIC RESPONSE.
WE CALL IT PVH AND WE'VE
USED MICE AND GUINEA PIGS
AND WE HAVE FOUND THAT
THIS IS REALLY A CLASSIC
DELAYED HYPER SENSITIVE
RESPONSE FOR ALL YOU
ALLERGISTS AND
IMMUNOLOGISTS OUT THERE
AND WE HAVE BEEN THE
EFFECTER CELLS THAT ARE
INVOLVED AND IT'S A TH1
TYPE OF RESPONSE AND WE'VE
FOUND AN INTERESTING ROLE
THAT IS REGULATORY FOR
GAMMA DELTA T CELLS AND
FEMALE ANIMALS AND HUMANS
EXPERIENCE MORE SEVERE
OUTCOMES.
THIS WORK WAS DONE BY MY
TWO FORMER POSTBACS SO I
HAVE TO GIVE THEM A SHOUT
OUT.
SO WE HAVE MODELS.
WE'VE GOT, WE KNOW WHAT IS
CAUSING -- WE WANT TO KNOW
WHAT IS CAUSING THIS DTH
RESPONSE SOUR APPROACH IS
ACTUALLY RUDIMENTARY TO
COMING UP WITH A BETTER
VACCINE.
SO WE'RE TAKING WHICH
KNOCK OUT SO THE SO THIS
IS A 22 GENETIC PORTION
RIGHT HERE AND THE SO ALL
YOUR BACK TER
Y'ALLOLOGISTS KNOW THAT
THIS IS A APPARATUS THAT
SITS ON THE OUTSIDE OF THE
BACTERIA AND IT SPITS OUT
PRE TEENS AND THAT HE
BASICALLY HELP THE
BACTERIA TO ESTABLISH ITS
SURVIVE IN THE HOST SO WE
KNOCK THIS LOCUS OUT AND
WE FOUND THE STRAIN WAS
AVIRULENT SO WE IDENTIFIED
ANOTHER BEYOND LPS AND WE
THOUGHT THIS WOULD BE A
GREAT VACCINE CANDIDATE
BECAUSE OF ITS AR VIRULENT
WE CAN GET IT EXEMPTED
FROM THESE REGULATIONS
BECAUSE IT WOULD BE MORE
SAFE TO WORK WITH IN LOWER
CONTAINMENT SO THAT'S IN
THE PROCESS BUT IT'S A LOT
OF PAPERWORK AS YOU CAN
IMAGINE.
SO I JUST WANT TO SHOW YOU
QUICKLY SOME OF THE DATA
THAT WE HAVE THAT SHOW
THAT THESE VACCINES ARE
QUITE PROTECTIVE IN FACT
THEY'RE THE SAME LEVEL AS
OUR GOLD STANDARD OR Q VAX
SO WE VACCINATE GUINEA
PIGS AND WE INFECT THEM
WHICH IS OUR GOLD STANDARD
OF A ANIMAL OF Q FEVER AND
THIS IS A BODY TEMPERATURE
GRAPH.
FEVER IS A HALLMARK CHER
TURRIS TICKS.
GUINEA PIGS HAVE A 38 TO
39° CELSIUS BODY
TEMPERATURE.
FEVER AROUND 39.5 SO THESE
NOT A MALLS HAVE NOT BEEN
VACCINATED BUT THEY'RE
INFECT SOD THEY GET FEVER
THAT LASTS FOR A WEEK AND
IT'S HIGH FEVER.
NOW WHEN WE VACCINATE WITH
Q VAX YOU SEE THE ANIMALS
HAVE LOW GRADE TRANSIENT
FEVER SO THEY LOOK A LOT
BETTER THAN THE
UNVACCINATED ANIMALS AND
OUR VACCINE, LOOKS SIMILAR
TO Q VAX WITH FEVER AND
BODY WEIGHT CHANGE AND
OTHER HALLMARKS OF THIS
DISEASE SO OF COURSE, YES,
THEY'RE PROTECTED SO ARE
THEY LEG REACTIVE.
SO I WANT TO SHOUT OUT
CRYSTAL MY TECHNICIAN FOR
DOING ALL THE OF THIS
WORK, HERE WE'RE USING A
GUINEA PIG MODEL AND WE
HAVE SITUATIONS LIKE THIS.
SO WE TESTED OUR DIFFERENT
VACCINES AND OUR GUINEA
PIG MODELS AND I KNOW
THERE'S A LOT GOING ON
HERE BUT I'LL WALK YOU
THERE IT.
THIS IS THE AREA OF
REDNESS THAT APPEARS IN
THE CIRCULAR FASHION AT
THE SKIN TESTING SITE AND
IT'S THROUGHOUT THE WHOLE
THREE WEEKS OF MONITORING.
WE SEE THAT ANIMALS THAT
ARE DOING Q VAX HAVE A
HIGH AREA IS SIGNIFICANT
COMPARED TO ALL THE
CONTROLS BUT WE HAVE TWO
DIFFERENT KNOCK OUT
STRAINS.
WE HAVE A NINE MILE ONE
AND WE HAVE ANOTHER
BACKGROUND I DON'T HAVE TO
TELL YOU ABOUT AND THEY DO
EXPRESS AND THIS IS KIND
OF BOLSTERED BY HISTOLOGY
SCORING AND OTHER QUANTITY
IMPORTANCE THAT WE HAVE
DONE AND SO ONE MORE THING
I WANT TO TELL YOU ABOUT
BEFORE I'M DONE THAT IS
RELATED TO THIS BUT IT'S
EXCITING.
WE CAN FOCUSED ON
IMPROVING OF MODEL WE WORK
WITH RTV AND GET THE WHOLE
GENOME ANNOTATED FOR THE
GUINEA PIG WHICH IS MOST
PEOPLE USE AND WE'RE
ACTUALLY ABLE TO PERFORM
SINGLE CELL SEQUENCES
AFTER VACCINATION ON THE
SPLEEN TO TRY TO GET MUCH
MORE RESOLUTION INTO WHAT
IS ACTUALLY HAPPENING IN
PROTECTION.
WE'RE SEEING DIFFERENCES
IN FEMALES VERSUS MALES
AND IN VACCINATED VERSUS
UNVACCINATED BUT I JUST AM
REALLY EXCITE BESIDE THIS
DATA SO I HAD TO THROW IT
IN AND THEN THIS IS MY
PROGRAM AGAIN.
JUST LIKE DREW SAID.
THERE'S NOT A LOT TIME TO
TALK ABOUT WHAT WE'RE
DOING.
WE HAVE THIS HOLISTIC ONE
HEALTH APPROACH WHEN WE
LOOK AT IT.
WE'RE INTERESTED IN THE
ENVIRONMENT.
HOW DOES IT SURVIVE IN
SOIL.
CAN IT LIVE IN THE WATER?
AND WE USE ALL THE
TECHNIQUES I TOLD YOU
ABOUT TO LOOK AT THIS AS
WELL AS DEVELOPING BETTER
COUNTERMEASURES LIKE THE
VACCINE.
AND SO I WOULD LIKE TO
THANK KNOWN A. CHRIS, DREW
ESPECIALLY FOR ORGANIZING
THIS WHOLE RESEARCH
FESTIVAL.
IT'S SUCH A TREAT TO COME
HERE AND TALK TO YOU ALL.
I'M GOING TO GIVE A SHOUT
OUT TO MY GROUP.
MATT MY POSTBAC IS UP
THERE AND HE IS GIVING A
POSTER SO CHECK THAT OUT
AND CRYSTAL MY TECHNICIAN
RIGHT HERE AND JOHN ARE
GRAD STUDENTS AND THEY'RE
AWESOME AND MY FORMER
POSTBAC, MAHALA IS IN THE
VRC AND SHE'S DOING HER
GRADUATE WORK AT GEORGE
WASHINGTON AND PEEK A POO
IS ACROSS THE STREET
GETTING HER MD PH.D.
THANK YOU THE IRS PROGRAM
IS FABULOUS AND ALL THE
SUPPORT AND ALL THE
AMAZING RESOURCES WE HAVE
AT NIH.
AND I'M TRYING TO GET UP
TO SPEED SO I HAVE A QR
CODE FOR MY LAB.
THAT'S IT.
[APPLAUSE]
>>WE HAVE OUR MANDATORY
QUESTION COMING FROM
ON-LINE AND IT'S FROM OUR
COLLEAGUE HOWARD YOUNG.
DOES THIS BUG INDUCE TYPE
ONE OR TYPE 111 INTER
NEURONS?
>>THE ONLY ONE I HAVE
SEEN INTERFERON GAMMA BUT
WE DON'T KNOW THAT MUCH
ABOUT IT ESPECIALLY IN
HUMANS SO UNFORTUNATELY I
CAN'T ANSWER THAT VERY
WELL.
IS I DON'T KNOW THE
DIFFERENCES BETWEEN
VACCINATION AND I IMAGINE
IT WOULD BE SIMILAR SO
SORRY I DON'T HAVE ANSWERS
BUT WE WILL SOON.
>>THAT'S ALL FROM ON-LINE
AT THE MOMENT.
ANYONE IN THE AUDIENCE?
IS.
>>MICE DON'T GET IT?
>>THEY'RE VERY RESISTANT
TO INFECTION SO THE END
POINT YOU HAVE TO USE ARE
OTHER THAN BODY WEIGHT,
THEY GET EXPLAIN A MEG
ALLEY BUT THEY DON'T HAVE
A SIMILAR RESPONSE.
>>IS THAT CLEAR WHY?
>>NO.
NO.
THERE HAVE BEEN A COUPLE
STUDIES ON MICE LIKE THEY
LOOKED AT DIFFERENT
STRAINS AND SOME ARE MORE
SUSCEPTIBLE THAN OTHERS
BUT IT'S BECAUSE OF THE TH
1 BIAS.
>>I WAS CURIOUS ABOUT
YOUR LPS AND WHAT
HAPPENED.
DO YOU KNOW THE MECHANISM
WHY THEY LOSE LPS WHEN YOU
CULTURE THEM?
>>YES.
SO ACTUALLY ROUGHLY THEY
LOSE THIS BIG GENETIC LIKE
LOCUS THAT ENCODES A LOT
OF DIFFERENT GENES AND
WITH LPS BUT WE ACTUALLY
DISCOVERED A SINGLE POINT
MUTATION THAT'S CAUSED A
LOT OF ISSUES AND I'M
TALKING ABOUT LAND OWE
LYNCH SO YEAH IT HASN'T
GOTTEN US IN TROUBLE BUT
IT'S A CONTENTIOUS
DISCOVERY BUT IT'S GENETIC
WHEN THEY'RE IN CULTURE.
YEAH.
WONDERFUL PRESENTATION.
THANK YOU, CARRIE.
[APPLAUSE]
I CAN'T HELP BUT THINK OF
YELLOW STONE EVERY TIME I
HEAR ABOUT MONTANA BUT
THAT'S JUST ME.
OUR NEXT PRESENTER EMILY
RICOTTA.
SHE'S PART OF THE 2022 IRS
COHORT.
SHE'S WITH NIAID AS WELL.
WITH THE EPIDEMIOLOGY AND
DATA MANAGEMENT UNIT.
GRADUATED FROM THE
UNIVERSITY OF BASSEL.
AM I PRONOUNCING THAT?
IN EPIDEMIOLOGY.
GOOD TO HAVE YOU.
THE FLOOR IS YOURS.
>>NOW FOR SOMETHING
COMPLETELY DIFFERENT.
WITH SEW LET'S SEE HERE.
IF YOU HAVEN'T BEEN OUT TO
VISITS RML I RECOMMEND IT.
IT'S BEAUTIFUL.
I LOVE TOURING AROUND THE
BSL FLOOR.
SO THANK YOU ALL SO MUCH
FOR HAVING US HAVING THIS
SESSION.
IT'S GREAT TO HEAR ALL THE
OTHER IRS FELLOWS TALKS
AND SHARE OUR RESEARCH
WITH YOU.
I'M GOING TO GO THE
TOTALLY OPPOSITE DIRECTION
AND I'M AN EPIDEMIOLOGIST
SO WE FOCUS ON THE HIGH
LEVEL SO I WILL GIVE YOU A
REEL HIGH LEVEL VIEW OF
THE THINGS THAT MY GROUP
DOES AND IF YOU HAVE
FURTHER QUESTIONS OR WANT
TO DIE DEEP YOU HAVE TO
COME TALK TO US.
SO MY IS FOCUSED ON THE
STUDY OF EPIDEMIOLOGIC
DATA.
BOTH TO ANSWER QUESTIONS
ABOUT DISEASE RISK LIKE
YOU WOULD THINK ANY NORMAL
EPIDEMIOLOGY STUDY DOES
BUT OF ITS OWN ENTITY TO
BE STUDIED AND UNDERSTOOD
AND STRENGTHENED AND YOU
CAN SEE OVER HOA THAT DATA
MANAGEMENT AND THE
COLLECTION OF DATA AND
PROCESSING OF DATA REALLY
LASTS THROUGHOUT THE
LIFETIME OF A STUDY AND SO
THAT'S WHERE WE NEED TO BE
PAYING ATTENTION TO THESE
THROUGHOUT THEIR LIFETIME.
HOW ARE WE TRYING TO DO
THIS RESEARCH?
SO WE'RE UNDERSTANDING AND
IMPROVING DATA COLLECTION
AND MANAGEMENT
SPECIFICALLY USING NON
RANDOMIZED STUDIES.
WHEN YOU THINK OF CLINICAL
EVIDENCE YOU ARE TRYING OF
RANDOMIZED CONTROL TRIALS
BECAUSE THERE'S A GOLD
STANDARD BUT THERE ARE
MANY SITUATIONS WHEN WE
CAN'T CONSTRUCT AN RCT OR
IT'S NOT ETHICAL TO
CONDUCT AN RCT.
MANY TIMES THIS IS AT THE
BEGINNING OF A PANDEMIC OR
AN OUTBREAK WHERE WE JUST
DON'T HAVE THE TIME WITH
THE NUMBER OF CASES TO GET
PEOPLE ENROLLED.
AND SO ONE OF THE THING
WIND CHILL PUBLISHED IN
MEDICINE WAS THIS
VIEWPOINT STAYING WE NEED
TO IMPROVE OBSERVATIONAL
STUDIES.
WE NEED TO STANDARDIZE THE
METHODS AND PUTTING SOME
CONTROLS IF PLACE SO THAT
WE AREN'T JUST HAVING A
TON OF REAL ICKY GARBAGEY
DATA OUT THERE AT THE VERY
BEGINNING AND WE MAKE
POLICY OFF OF.
I'M NOT SURE IF YOU
REMEMBER THE HYDROXY COLOR
KIN EPISODE BUT THIS IS A
GREAT EXAMPLE.
SO HOW ARE WE TRYING DO
THIS?
WELL ONE OF THE PROJECTS
WE'RE WORKING ON IS TRYING
TO UNDERSTAND WHAT DATA
USING NON RANDOMIZED
STUDIES GETS COLLECTED
EARLY AND OUTBREAKS.
AND SO WE'RE DOING A
RETROSPECTIVE ANALYSIS
WHERE WE PICK A NUMBER OF
DIFFERENT OUTBREAKS OF
IMPORTANCE THAT YOU CAN
SEE HERE AND WE'RE TRYING
TO UNDERSTAND WHAT DATA
WAS PUBLISHED, WHAT GOT
PUT INTO THE LITERATURE IN
THE FIRST 12 MONTHS OUT
AFTER OUTBREAK WAS
DECLARED.
WE'RE REALLY INTERESTED IN
FOCUSING ON THAT EARLY
INFORMATION AGAIN.
WAS GETTING OUT THERE?
WHAT'S GETTING INTO
POLICY.
WHAT'S INFLUENCING FURTHER
RESEARCH.
IF YOU WANT TO HEAR MORE
ABOUT THIS, CHECK OUT MY
POSTBAC EMMA'S POSTER I
BELIEVE IT'S NUMBER 19
TODAY.
SO YOU CAN LEARN MORE
ABOUT THAT.
WE'RE ALSO INTERESTED IN
EVALUATING DATA MANAGEMENT
CAPACITY.
SO THE ABILITY TO ACTUALLY
COLLECT DATA, TAKE IT,
CLEAN IT, USE IT, SHARE IT
AND IN AREAS AT HIGH-RISK
FOR INFECTIOUS DISEASE
SPILL OVER AND CLIMATE
CHANGE.
THIS WAS ACTUALLY THE
SUBJECT OF AN NIEHS
CLIMATE CHANGE AND HEALTH
AWARD THAT WE WERE GIVEN
AT THE BEGINNING OF THIS
YEAR.
WE ARE TRYING TO QUANTIFY
DATA MANAGEMENT'S
CAPACITIES AS AN
INDEPENDENT RISK FACTOR
FOR INFECTIOUS DISEASE
SPILL OVER.
THIS IS MY POSTDOC FAST
OWE IS LEADING THIS WORK
IN COLLABORATION WITH
Dr. COLIN KARLSSON AT
GEORGETOWN UNIVERSITY.
THERE'S LARGE-SCALE
MATHEMATICAL MODELS WHERE
WE CAN EVALUATE INFECTIOUS
DISEASE SPILL OVER RISK
GLOBALLY.
SO WHAT WE'RE DOING IS
WE'RE REVIEWING LARGE
CATER DOCUMENTS SUCH AS
THE GLOBAL HEALTH SECURE
CAN TEE INDEX, THE WORLD
HEALTH ORGANIZATIONS
INTERNATIONAL HEALTH
CATERS AND THINGS LIKE
THAT TO SEE WHAT ARE THE
MEASURES OF DATA
MANAGEMENT CAPACITY THAT
ALREADY EXISTS WHEN
THEY'RE NOT FINDING MANY.
BUT CAN WE USE THAT?
CAN WE CREATE A SCORE
INDEX TO MODEL THIS AND
QUANTIFY IT AND SEE HOW IT
IS THE RISK OF SPILL OVER.
AGAIN BEING INTERESTED IN
THAT EARLY EVIDENCE THAT
GETS PUT OUT INTO THE
LITERATURE, WE ARE LOOKING
AT PRE PRINTS AND THEIR
CORRESPONDING
PEER-REVIEWED POST PRINT
AS I WILL REFER TO THEM.
THAT WERE ACTUALLY
INCORPORATED INTO EARLY
U.S. GOVERNMENT COVID-19
POLICY.
SO WE ARE LOOKING AT THE
DEPARTMENT OF HOMELAND
SECURITY'S MASTER QUESTION
LIST AS WELL AS THE CDC'S
NIOSH WHICH IS THE
NATIONAL CENTER FOR
OCCUPATIONAL HEALTH, THEIR
WEEKLY COVID
RECOMMENDATIONS, THEY SITE
16% OF THE CITATION S WITH
PRO PRINTS.
26% OF THE THINGS THEY
INCLUDED WEREN'T
PEER-REVIEWED OUGHT ALL
NOR WERE THEY GOING TO BE.
WE'RE TRYING TO UNDERSTAND
WHAT THE QUALITY OF THAT
WAS.
DID THEY GET PUBLISHED IN
A PEER REVIEW JOURNAL.
LUCKY MANY OF THEM DID.
WHAT WERE THE CHANGES AND
HOW LONG DID IT TAKE TO
INCORPORATE CHANGES BACK
INTO POLICY.
WE'RE DOING THIS USING
NATURAL LANGUAGE.
THESE ARE TWO OF MY
PAPERS.
ONE WAS A PRE PRINT AND
ONE WAS THE PUBLISHED, NOT
INCLUDED IN POLICY BUT
WHAT WE DO IS WE TAKE THE
PRE PRINT AND THE
PUBLISHED ONE AND WE
SENTENCE ALIGNMENT SO YOU
CAN SEE AN EXAMPLE RIGHT
HERE OF TWO SENTENCES THAT
ARE ALGORITHM PREDICTED
WITH HIGH LEVELS OF
CERTAINTY TO BE THE SAME
SENTENCE WHICH IS GREAT
BECAUSE THEY ARE.
BUT IF YOU SEE DOWN BELOW,
WE ACTUALLY CAN TAKE THIS
A STEP FURTHER AND WE CAN
DO, USE NATURAL LANGUAGE
PROCESSING AND PRO TRAINED
ALGORITHMS, IF ANY OF YOU
ARE FAMILIAR WITH BIO
BIRCH OR SIDE MODEL WE CAN
DO INTENTION
CLASSIFICATION.
IT HELPS US DETERMINE WHAT
THE INTENT OF THE CHANGES
WERE SO IN MY SENTENCE YOU
SEE INDIVIDUALS WITH
CHRONIC ILLNESS AND OTHER
CO MOR MID BEE ARE LESS
LIKELY TO REDUCE TO BE
VACCINATED.
THAT'S IN THE PRE PRINTS.
IN THE PUBLISHED VERSION,
INDIVIDUALS WITH
CO-MORBIDITIES ARE NOT
LESS LIKELY TO REFUSE
VACCINATION.
THAT'S A BIG CHANGE, HUH.
WE ACTUALLY SPENT TIME
DOING ANOTHER WHOLE ROUND
OF SURVEYING AND ANALYSIS
AND THEN OUR CONCLUSIONS
CHANGED.
AND THIS WAS IN POLICY,
AND THIS DIDN'T GET
REINCORPORATED, WE COULD
BE MAKING POLICY OFF OF
DATA THAT IS NO LONGER
RELEVANT WHEN WE HAVE I AM
PROVED OUR STUT HE'S AND
OUR SAMPLE SIZE.
THIS IS A LARGE CORP IS OF
PUBLICATIONS THAT WE'VE
ACTUALLY PULLED OUT OF
REAL GOVERNMENT POLICIES
SO WE'RE VERY EXCITED TO
GO FORWARD THIS STUDY.
WE ALSO ARE INTERESTED IN
TRYING TO GET EXPERT INPUT
ON HOW WE STANDARDIZED THE
CONDUCT OF NON RANDOM
SIZED STUDY.
SO JUST THURSDAY AND
FRIDAY OF THE LAST WEEK WE
HOSTED NEXT PERTH WORKSHOP
AND WE BROUGHT PEOPLE FROM
ALL OVER THE WORLD TO COME
TO NIH AND TALK TO US
ABOUT THEIR -- WHAT WE SEE
AS THE GAPS IN THE
CHALLENGES ARE IN
CONDUCTING STUDIES IF YOU
ARE IN LOW TO MIDDLE
INCOME COUNTRIES OR IF YOU
ARE IN THE U.S. TRYING TO
DO COHORT STUDIES IT'S
DIFFICULT.
WE HAD DATA COLLECTORS, WE
HAD EPIDEMIOLOGISTS, WE
HAD AN INTERNATIONAL
HEALTH LAWYER WHO IS
CURRENTLY WORKING ON
HELPING DRAFT THE U.N.
PANDEMIC TREATY.
WE HAD A WONDERFUL GROUP
OF PEOPLE.
IT WAS REALLY AWESOME TO
HOST THIS YESTERDAY.
YOU CAN SEE US ALL HERE
WORKING IN BREAK OUT
GROUPS AND SMALL GROUPS
TRYING TO BRAINSTORM FOR
THIS AND WE'RE HOPING
THESE WILL COME OUT IN A
PEER REVIEW JOURNAL HERE
IN THE NEXT FEW WEEKS.
ALL RIGHT SOLVE TO SWITCH
GEARS A LITTLE MANY OF
IT'S FOCUSING ON DATA AS
ITS OWN ENTITY RIGHT BUT
EPIDEMIOLOGIST WE HELP
GENERATE DATA FOR SOME OF
THESE STUDIES.
AND SO NOW I'M GOING TO
TALK ABOUT SOME OF THE
MORE TYPICAL STUDIES THAT
YOU WOULD THINK OF WHEN
YOU THINK RESEARCH.
THE FIRST IS OUR PERSIST
STUDY.
THIS IS A LONGITUDINAL
STORY EVALUATING THE
IMMUNE RESPONSE TO COVID
VACCINES AND PEOPLE WITH
IMMUNE DISORDERS AND WE
HAD SIM POLLS FROM
APRIL 2021 THROUGH
JULY 2023.
WE JUST FINISHED SAMPLE
COLLECTION.
WE HAVE 308 PARTICIPANTS
ENROLLED.
235 OF THEM HAVE IMMUNE
DISORDERS OF A VARIETY OF
DIFFERENT TYPES.
THIS IS INBORN ERRORS OF
IMMUNITY SUCH AS PRIMARY
ANTI-DEFICIENCIES AND
SIGNALING PATHWAY
DEFICIENCIES AND WE HAVE
SECONDARY IMMUNE DISORDERS
LIKE PEOPLE WHO HAVE BEEN
TAKING PROTECTION A PLAN
AND HAD AN ORGAN
TRANSPLANT.
WE HAVE 73 HEALTHY
VOLUNTEERS.
THESE INDIVIDUALS ARE OVER
THE RANGE OF I BELIEVE OUR
YOUNGEST WAS SIX-YEARS-OLD
UP TO SOMEONE WHO 90 SO WE
HAVE A LARGE DISTRIBUTION
OF PEOPLE PARTICIPATING.
WE WERE ABLE TO COLLECT
1,166 INDIVIDUAL TIME
FLAMES AND THESE FROM BASE
LINES OF THE FOUR PEOPLE
WHO WERE VACCINATED UP
THROUGH 12 MONTHS POST
DOSE FIVE.
SOME OF THESE PEOPLE ARE
VERY IMMUNE DEFICIENT SO
THEY WERE ABLE TO GET
VACCINES EARLY ON.
AND WE COLLECTED A TON OF
SAMPLES.
WE HAVE WHOLE BLOOD MICRO
SAM PLEASURES, PLASMA, DNA
SO IF ANYBODY WANTS TO
COLLABORATE, PLEASE GIVE
ME A CALL.
ONE OF OUR BIG FINDINGS
WAS THAT WE DID AN INTERIM
ANALYSIS WHERE THE FIRST
YEAR WHERE WE LOOKED AT
195 PEOPLE WITH IMMUNE
DISORDERS AND 35 OF OUR
HEALTHY VOLUNTEERS.
AND WE FOUND THAT THE ANTI
SPIKE IGG RESPONSE WAS
COMMON WHICH IS GREAT SO
AFTER THE SECOND DOSE, 88%
OF OUR PEOPLE WITH IMMUNE
DISORDERS HAD SOME SORT OF
POSITIVE ANTIBODY RESPONSE
TO THE VACCINE THAT GREAT
NEWS.
AFTER SIX MONTHS, THE
THIRD DOSE, THIS WAS UP TO
93%.
SO IT SHOWS THAT GIVING
THESE MULTIPLE DOSES IN
PEOPLE WITH IMMUNE
DISORDERS CAN MAYBE REALLY
HELP GET THAT LEVEL OF
POSITIVITY UP.
HOWEVER, JUST BECAUSE THEY
WERE POSITIVE DOES NOT
MEAN THAT THEY ARE
PRODUCING ANTIBODIES AT
THE SAME MAGNITUDE AS THE
HEALTHY VOLUNTEERS AND
WHAT WE FOUND IS THAT
THEIR ANTIBODY RESPONSE
LEVEL WAS NEVER HIGHER
THAN A THIRD OF THAT WHAT
HEALTHY VOLUNTEERS CAN
MAKE AND SO WE CAN'T
ACTUALLY SAY WITH ANY
CERTAINTY, YOU KNOW, HI,
FOLKS, YOU HAVE RESPONDED
TO THE VACCINE BUT WE
DON'T KNOW IF YOU ARE
PROTECTED AND THAT WAS
SOMETHING REALLY HARD TO
SAY TO OUR PARTICIPANTS
OVER AND OVER AGAIN
THROUGHOUT THIS STUDY BUT
YOU KNOW WE ARE STILL
WORKING HARD.
WE'VE BEEN LOOKING AT A
NUMBER OF DIFFERENT
VARIANTS.
WE DID FIND GOOD CROSS
COVERAGE, CROSS BINDING OF
THESE ANTIBODIES TO MANY
OF THE VARIANTS WHICH
ALTHOUGH DIDN'T DECREASE
TO OMICRON WHICH IS TO BE
EXPECTED AND WE LOOKED TO
SEE WHETHER THESE
ANTIBODIES COULD PSEUDO
NEUTRALIZE.
THE RECEPTORS FOR COVID.
WHETHER THAT RESPONSE WAS
CORRELATED WITH THE
ANTIBODY LEVEL.
WE SEE A LOT OF PEOPLE
SAYING OH, YOUR ANTIBODY
LEVEL PRE TICKETS HOW
PROTECTED YOU ARE FROM THE
VACCINE.
IS THAT TRUE?
WELL, IT DEPENDS.
IT DEPENDS ON THE VARIANT
AND HOW MANY VACCINES AND
IT DEPENDS ON WHAT YOUR
IMMUNE CONSTITUTION IS.
THERE'S MORE TO BE DONE
THERE.
WE DID JUST HAVE OUR FIRST
PAPER THAT WAS ACCEPTED TO
SCIENCE ADVANCES LAST
WEEK.
WE'RE JUST IN PRESS.
THEY WERE OUR FIRST
AUTHORS ON THAT AND THEY
DID SO MUCH WORK.
CHECK THAT OUT SOON.
ONE OF THE CONTINUING
PROJECTS, SO BECAUSE I'M
AN EPIDEMIOLOGIST I
INSISTED ON DOING ACTIVE
SURVEILLANCE OF COVID
BREAK THROUGH INFECTIONS.
SO LITTLE OVER HALF SENDS
THIS SALIVA WHICH WE
TESTED FOR COVID.
THEY CAN ALSO TELL FUSS
THEY DEVELOPED ANY COVID
EX WE WOULD SEND THEM A
TEST AND WE HAVE ABOUT A
HUNDRED OF OUR
PARTICIPANTS GOT A BREAK
THROUGH INFECTION AT SOME
POINT.
NOW THE GOOD NEWS WAS THAT
WE ONLY HAD ONE PERSON WHO
HAD DEAL AND NOTHING
BEFORE THAT.
WE WERE PANICKED OUR ESSAY
WASN'T WORKING BUT IT
WORKED FINE WHEN YOU GOT
OMICRON.
SO WE'RE EVALUATING THE
TIME IT TAKES TO GET
INFECTION.
HOW MANY DOSES THIS COULD
BE -- DOES THAT PREDICT
ANYTHING?
BUT I'M NOT GOING TO SPOIL
THIS WAS MCKENZIE IS
PRESENTING AT POST
EASTBOUND NUR 20 TODAY SO
CHECK THAT ONE OUT.
THE LAST THING I'M GOING
TO COVER, EPIDEMIOLOGY IS
REALLY A BROAD SET 6
METHODS AND WE COLLABORATE
WITH A LOT OF DIFFERENT
PEOPLE AND THAT'S ONE OF
THE THINGS THAT MAKES MY
JOB REALLY COOL AND IT'S
ONE OF THE REASONS I DO A
LOT OF INTERESTING SCIENCE
WITH A LOT OF REST OF YOU
SO THIS IS AN EXAMPLE OF
THAT STUDY, I'M
COLLABORATING WITH Dr.
KAITLYN SADLER AND FROM
NIBIB TO LOOK AT THE
CONSERVED AND DIVERGENT
IMMUNE RESPONSE TO
TRAUMATIC INJURY SO THEY
HAVE COLLECTED 1,000
SAMPLES FROM PEOPLE WHO
EXPERIENCED A TRAUMA AND
50 HEALING' CONTROLS AND
THEY TESTED THEM FOR SO
MANY BIOMARKERS AND THEY
ALSO HAVE A LOT OF
CLINICAL DATA.
WHERE I COME IN IS TO
DISCUSS SAMPLE SIZE, THE
DEVELOPMENT OF THE MODEL
THAT WE'RE BUILDING THAT
WE'RE USING, STATISTICAL
ANALYSIS, PUTTING THINGS
IN CONTEXT.
SO ONE OF THE THINGS WE'VE
BEEN ABLE TO IS WE'VE BEEN
ABLE TO Z. GREAT, IT DOES
APPEAR THAT CONTROLLING
FOR SOME OF THESE OTHER
VARIABLES, THERE'S AN UP
REGULATED RESPONSE IN SOME
BIOMARKERS RELATIVE TO
HEALTHY PEOPLE AND THERE'S
A DOWN REGULATED OF SOME
BIOMARKERS RELATIVE TO
HEALTHY PEOPLE.
WHAT I'M REALLY
INTERESTING IS HOW AN
INFECTIOUS DISEASE CHANGES
THIS RELATIONSHIP.
SO YOU CAN SEE IN THIS
BOTTOM FIGURE HERE, THE
BLUE BARS ARE PEOPLE WHO
EXPERIENCED TRAUMA BUT DID
NOT HAVE COVID HAVE NO
EVIDENCE FOR COVID
INFECTION AND VERSUS
HEALTHY PEOPLE.
AND THE PINK BARS ARE THE
PEOPLE WHO HAD COVID AND
ALSO TRAUMA SO REALLY BAD
DAY FOR THEM RELATIVE TO
THE HEALTHY PEOPLE AND YOU
CAN SEE THAT NOW THINGS
GET A LITTLE DIFFERENT.
MORE OF A POPULATION
LEVEL, HOW DOES HAVING AN
INFECTIOUS DISEASE IMPACT
YOUR BODY'S ABILITY TO
RESPOND TO A TRAUMA AND
ALSO HOW DOES HAVING A
TRAUMA MAY BE RESPOND TO
YOUR ABILITY TO COPE WITH
AN INFECTIOUS DISEASE
MAYBE IT'S AN INFECTION, A
SURGICAL SITE INFECTION OR
WOUND INFECTION OR
SOMETHING YOU GET LATER
DOWN THE LINE IF YOUR BODY
IS STILL RECOVERING FROM
TRAM A WITH THAT WE
COLLABORATE WITH ALL THE
OF INDIVIDUALS
INTRAMURALLY AND
EXTRAMURALLY AT MAIN
CAMPUS, RML, ACROSS THE
WORLD AND IF YOU ARE
INTERESTED IN GETTING
INVOLVED OR ANY SORT OF --
YOU HAVE AN
EPIDEMIOLOGICAL STUDY YOU
ARE INTERESTED IN TALKING
ABOUT YOU NEED TO HELP
DESIGN YOUR STUDY PROCESS,
ANYTHING LIKE THAT.
PLEASE GIVE US A -- LOOK
US UP.
WE HAVE A HUGE STUDY TEAM.
WE HAVE A HUGE NUMBER OF
COL AT RATERS AND I WANT
TO THANKLY SAY THANK YOU
TO MY UNIT AND THEY'RE
AMAZING AND YOU CAN CHECK
OUT -- I DIDN'T DO A QR
CODE BUT HERE IS OUR
WEBSITE.
IT HAS A HEINE' URL SO
E-MAIL ME IF YOU HAVE
QUESTIONS, I CAN TAKE
ANYTHING RIGHT NOW AND
CHECK OUR OUT WE ARE
SIGHT.
[APPLAUSE]
WEBSITE.
>>I DO HAVE A QUESTION
ON-LINE BUT IT'S PRETTY
OPEN-ENDED AND PROBABLY
APPLICABLE TO ANYONE.
HOW DO YOU THINK THAT THE
INFORMATION YOU AGAIN
RATGENERATED CAN BE
BETTER UNDERSTOOD BY THE
PUBLIC?
>>INTERESTING.
I THINK THAT IN GENERAL, I
PERSONALLY AND IN GENERAL
THINK THAT WE COULD DO A
LOT BETTER OF PUTTING OUR
INFORMATION IN CONTEXT
THAT IS MEANINGFUL TO THE
GENERAL PUBLIC.
SO RATHER THAN OH, YES,
COVID VACCINES WILL
PREVENT COVID, FINE.
WHAT DOES THAT MEAN FOR
YOU AND YOUR COMMUNITY?
WHAT DOES IT MEAN FOR YOUR
KIDS IN SCHOOL?
WHAT DOES IT MEAN FOR YOUR
SICK AUNT WHO YOU WANT TO
SEE AT CHRISTMAS?
YOU KNOW, IF WE TAKE OUR
RESULTS AND WE TRY TO PUT
THEM IN CONTEXT THAT'S
MEANINGFUL TO THE PEOPLE
TO WHOM WE'RE
GENERALIZING, THEY TEND TO
BE MER WILLING TO HEAR IT
AND IT MAKES A LOT MORE
SENSE.
>>RANDOM KIND OF COMMENTS
LESS QUESTIONS.
SO THE HIGH CROX --
RESEARCH INTRODUCE THAT
AND NOW THE EFFICACY IS
BEING REQUESTED.
THAT'S NOT EXAMPLE OF
POLICY CHANGE THAT I CAN
PACKETS US AND WE DO
ENVIRONMENTAL MICROBIOLOGY
SAMPLING AND WE FOUND THE
EPA REGULATIONS KEEP ON
DRAMATICALLY CHANGING SO
HOW DO YOU THINK YOUR WORK
IS GOING TO IMPROVE THAT?
>>INTERESTING.
I'M NOT SURE.
WE SHOULD TALK ABOUT THAT
LATER THOUGH.
THAT'S A GOOD THING.
THIS IS THE KIND OF THING
THAT YOU KNOW, WE DON'T
NECESSARILY ALWAYS THINK
OF IT AS RESEARCH OR, I
KNOW WE'RE REALLY RANDOM
WHEN IT COMES TO THE OTHER
NIAID INVESTIGATORS BUT
THIS IS THE KIND OF
RESEARCH WE DO LOOKING AT
THESE BROADER POLICY
IMPLICATIONS AND DATA MORE
BROADLY IN GENERAL CAN
REALLY HELP IMPACT THE
SCIENCE THAT HAPPENS IN
THE LAB EVEN BASIC SCIENCE
SO YEAH, LET'S TALK LATER.
I'M SUPER CURIOUS TO HEAR
MORE.
>>THANK YOU.
[APPLAUSE]
ANOTHER VERY WONDERFUL
SERVING.
THAT WAS DELIGHTFUL.
I WOULD LIKE TO INVITE MY
CO-CHAIR TO INTRODUCE THE
NEXT PRESENTER.
>> Parinaz Fathi: ALL
RIGHT.
SO NEXT UP WE HAVE Dr.
OYEBOLA OY E.S.O. LA WHO
IS PART OF THE 2023
RESEARCH SCHOLARS PROGRAM.
AND SHE'S ALSO IN NIAID
AND COMPLETED HER PH.D AT
CORNELL UNIVERSITY IN
IMMUNOLOGY AND INFECTIOUS
DISEASE.
>>HI, EVERYONE.
SO I AM ONE OF THE NEW
COHORTS FROM 2023 SCHOLAR
SO THE PROJECT I'LL BE
PRESENTING TODAY WAS DONE
IN MY PREVIOUS LAB.
SO IT WILL GIVE YOU AN
OVERVIEW HOW MY INTEREST
STARTED AND WHAT WE'LL BE
DOING IN MY PROGRAM.
THE WORK I'M PRESENT
ASPRESENTING IS
ALREADY PUBLISHED AND I
HAVE A QR CODE, I'M GOING
TO GIVE YOU A SNEAK PEEK
AND WHAT WILL PLAN TO DO
AND ANY PROGRAM.
SO I HAVE TWO POST BACKS
HERE, KELSEY AND LUCAS AND
HOPEFULLY THEY'LL PRESENT
NEXT YEAR SOLVE I WORK I'M
TALKING TO SOLDIER SIMILAR
TO WHAT WAS INTRODUCED.
AND LATER AND EXPERIENCE
AND THIS IS CONTEXT
DEPENDENCY AND VARIATIONS
AND REALLY WHAT GOT ME
INTERESTED IN THIS
RESEARCH SO IF YOU LOOK AT
MORTALITY TO COVID-19, YOU
SEE THE REGIONS WHERE
THEY'RE INFECTION HAVE
LOWER MORTALITY SO
SARS-CoV-2.
YOU CAN SUPER IMPOSE THIS
GRAPH ON MY OTHER DISEASE
AND COME TO THE SAME
CORRELATION THAT THERE'S
AN INVERSE CORRELATION
BETWEEN THE MORTALITY AND
MORBIDITY TO SARS-CoV-2.
SO CONTEXT METHODS.
AND ALONG THE SAME LINE
EARLY IN THE PANDEMIC
THERE ARE A LOT OF
RESEARCH THAT CAME UP SO
SUGGESTING THAT HELMINTH
PLAYS A ROLE BUT THERE WAS
NO MOUSE THEORY TO I AM
INTO AND THERE WAS DATA
COMING OUT FROM UTOPIA
SUGGESTING THERE WAS A
LINK BUT NO RESEARCH TO
SUPPORT THIS.
AND I UNDERSTAND WHEN I
WAS STARTING MY POSTDOC
CARRYING ALAN CHAIR LAB
PRESENTED THIS NICE STRAIN
AND THAT WERE GIVING BCG
WHICH IS A VACCINE TO
MICRO SEEN TO TUBERCULOSIS
SURVIVE BETTER THAN MICE
THAT WERE GIVEN SUB CUTE
OR MICE THAT DIDN'T GET
BCG.
WHAT THIS IS SUPPOSED TO
SHOW IS THAT THE RESPONSE
HAPPENS EARLY LIKE THE
PROTECTION HAPPENS EARLY
IN THE PATHOGENESIS OF
(INAUDIBLE).
QUESTION WE'LL BE
INTERESTED IN HOW DOES
HHELMINTH USING THIS
AND WE ALSO THEN USE THE
MOUSE MODEL WHICH SAY
MOUSE MODEL THAT THE AS
WELL AS THE MATH OWE
GENESIS OF THIS AFTER DAY
28 POST INFECTION WE CAME
UP WITH SARS-CoV-2.
WHAT YOU NOTICE IS THAT
THERE WAS REALLY NO
SIGNIFICANT DIFFERENCE
BETWEEN MICE THAT WERE CO
CURRENTLY EFFECTED WITH
THE MICE THAT WERE NOT
INFECTED SO JUST IN THAT
MAYBE CHRONIC HELMINTH
INFECTION DOESN'T PROTECT
AND IN REGION WHERE YOU
HAVE HELMINTH INFECTION
YOU HAVE IS THAT DURING
THE EARLY STAGE OF LIFE
THEY GET INFECTED, THEY
GET TREATED AND THEN YOU
CAN GET EXPOSED TO
SARS-CoV-2.
THE QUESTION SO ASK HOW
DOES PREVIOUS HELMINTH
INFECTION INFLUENCE A FORM
INFLUENCE THE PATHOGENESIS
OF SARS-CoV-2.
SO HERE IT'S DIFFERENT
THAT WE INFECTED MICE WITH
THIS IS IN IT'S ALSO
SELF-LIMITING SO BY DAY
SEVEN TO DAY EIGHT YOU
HAVE CLEARANCE SO AROUND
DAY 14 THE PARASITE IS
GONE AND WE COME AT DAY 28
SO THEY SURVIVE ALL OF
THESE MICE.
WE NOTICE THAT MICE THAT
WERE PREVIOUSLY INFECTED
AND THEN HAVE BETTER
SURVIVAL TO SARS-CoV-2.
WE ALSO OBSERVED A MICE
THAT WERE PREVIOUSLY
INFECTED WITH
SARS-CoV-2.
ALSO RECOVER FASTER THAN
THE CONTROL MICE
SUGGESTING THAT PREVIOUS
PRIOR CHALLENGE WITH
HELMET INFECTION COMES
PREVIOUS TO SARS-CoV-2.
SO THE QUESTION IS THEN IS
THIS EFFECTING
ESTABLISHMENT OF THE VIRUS
OR CLEARANCE OF THE VIRUS
SO IT'S A TWO PRONGED
QUESTION SO AFTER THIS WE
WE INFECTED K18 MICE WITH
RECEIPT LENS LAW CLEARANCE
AND LOOK AT VIRAL TYPES AT
DAY THREE AND DAY SEVEN
POST INFECTION.
DAY THREE HELPING US TO
GET AT ESTABLISHMENT OF
THE VIRUS AND DAY SEVEN
WITH CLEARANCE.
DAY THREE WE DIDN'T SEE A
DIFFERENCE SUGGESTING THE
VIRUS WAS NOT REALLY
EFFECTED.
BUT BY DAY SEVEN WE NOTICE
THAT AND CLEAR THE VIRUS
FASTER THAN THE CONTROL
MICE.
THE QUESTION THEN IS WHAT
ARE THE FEATURES OF THIS
RESPONSE AND WE DECIDED TO
USE SURE PATHOLOGY AND
RESPONSE AND WHAT YOUR
NOTICE IS THAT MICE THAT
WERE PREVIOUSLY EXPOSED IN
THE RESIDENTS HAVE A LOT
OF INFLAMMATION SO THERE'S
THIS INIF FLATION AND A
LOT OF I AM FOE SIGHTS IN
THE LUNGS COMPARED TO MICE
THAT WERE JUST EXPOSED.
SO BECAUSE WE KNOW THAT
LYMPH SIGHT ON THE CD-18
CELLS SO WE IN MICE THAT
WERE PREVIOUSLY HE IS
POSED TO AND THE CONTROL
MICE WE DECIDED WHILE
THERE WAS NO DIFFERENCE
AND EARLY IN THE
PERCENTAGE OF CD18 EARLY
AND BY DAY SEVEN WHEN
WE'RE HAVING THAT BETTER
CLEARANCE WE HAVE MORE CD8
CELL.
WHAT WE ALSO NOTICE IS
THAT THERE WAS HIGHER,
FASTER RECRUITMENTS OF
THESE CELLS IN MICE THAT
WERE PREVIOUSLY EXPOSED.
AT DAY THREE AS WELL AS
DAY SEVEN POST INFECTION.
SO ALL OF THESE SEARCHES
THAT IS AN INCREASE
RECRUITMENT AND
ACCUMULATION OF CD8
T-CELL.
WE NOTICED MICE PREVIOUSLY
EXPOSED HAVE MOST CD8T
CELLS COMPARED TO THE
COUNTERPART.
SO THE QUESTION WE THEN
ASKED IS THAT ARE THESE
CD8 T CELLS ARE THE VIRUS
IN MICE PREVIOUSLY EXPOSED.
WHAT WE DID WAS WE
INFECTED MICE AND
DEFLETTED THE CD8 T CELLS
USING DEPLETION AND COME
LATER WE (INAUDIBLE).
SO WHAT WE NOTICED WHEN WE
TAKEAWAY THE CD8 T-CELL
THE MICE BECOME AGGREGATED
SUGGESTING THAT THESE CD8
T CELLS ARE IMPORTANT IN
MICE EXPOSED TO THE
(INAUDIBLE) SO JUST TO
KIND OF TAKE A PAUSE, WHAT
I'VE SHOWN YOU SO FAR IS
THAT ONE THERE'S ENHANCED
CLEARANCE OF THE VIRUS IN
MICE THAT WERE PREVIOUSLY
EXPOSED.
AND THEY SURVIVE BETTER.
NOT AT DAY IS THREE BUT AT
DAY SEVEN POST INFECTION.
THAT IS INCREASED
PERCENTAGE AND NUMBERS OF
CD8 T CELLS IN MICE
PREVIOUSLY EXPOSED TO HELL
MINUTE AND IT'S ALSO IN
HANCE IN THESE MICE.
AND FINALLY, THAT THIS CD8
T CELLS IS INHEIGHTENED IN
GROUPS IN MICE PREVIOUSLY
INFECTED WITH N.
BRASILENSIS AND CRITICALLY
AND THIS IDEA OF
REMODELING AFTER HELMINTH
INFECTION IS REALLY NOT
NEW.
THEY HAVE SHOWN THERE'S
REMODELING OF TISSUE
FOLLOWING THE INFECTION
AND WE WANTED TO KNOW
WHETHER THIS IS IMPORTANT
IN THE ENHANCED.
IN THIS CASE.
SO THE APPROACH WE TOOK
WAS TO INFECT MICE WITH
NIPPOSTRONGYLUS AND THEY
CHARACTER EYES THE IMMUNE
RESPONSE USING SINGLE CELL
PARTICULAR KNOWLEDGE AND
WE NOTICED WE HAVE A AGAIN
THERE'S REMODELING AND WE
HAVE T-CELL LYMPH SIGHT
RESPONSE AND ACTIVATED
MAKE REFAGES IN MICE AND
IF WE LOOK TRANSCRIPTION
WE SEE THE TRANSCRIPTION
OR PROFILE OF MACROPHAGES
AND MICE PREVIOUSLY
EXPOSED IS DIFFERENT FROM
THEIR CONTROL MICE SO YOU
HAVE INCREASED ALTERNATIVE
TO MACROPHAGES BOTH IN THE
MACROPHAGE AS WELL AS IN
THE FALK ROW PAGES AND
ALSO YOU OBSERVED THAT
THIS MACROPHAGES HAVE
INCREASED SO YOU HAVE
INCREASED CHEMOKINES IN
MICE THAT WERE PREVIOUSLY
EXPOSED.
WE ALSO SAW THAT DCD14
CELL SUBSET SEEN AT 28
POST INFECTION HAVE A
DIFFERENT TRANSCRIPTION OF
PROFILE COMPARED TO THE
CONTROL MICE.
SUGGESTING THERE MIGHT BE
REMODELS OF THE HELMINTH
INFECTION THAT PERSISTS
LONG AFTER THE PARASITE IS
GONE.
AND I'M NOT SURE WE ALSO
OBSERVED THAT THERE ARE
EPIGENETIC CHANGES THAT
PERSIST UP TO DAY 45 POST
INFECTION IN MICE
PREVIOUSLY EXPOSED.
SO WE TRIED TO GET THE
MECHANISM WHICH IS
HAPPENING AND TO KNOW WHAT
IS RESPONSIBLE FOR THIS
ENHANCE NOT OF THE
RESPONSE THAT WE HAVE SEEN
IN MICE EXPOSED TO
SARS-CoV-2MENT I
MENTIONED ORDERS HAVE
SHOWN THE CCL16 PART WAYS
IS IMPORTANT FOR
LOCALIZATION AND THE
RECRUITMENT OF HERE AND
AGAIN WHEN WE LOOK IN MICE
PREVIOUSLY EXPOSED, YOU
SEE THERE ARE MORE OR 16
IN THE MACRO PAGES AND IN
THE ALTERNATIVE MACRO
PAGES AND EVEN AT DAY 28
POST INFECTION.
YOU SEE INCREASE MOUSE
INCREASE EXPRESSION OF
THIS CHEMO KEEN IN
MONOCYTES IN MACROPHAGES
AS WELL AS THE MICE THAT
WERE PREVIOUSLY EXPOSED.
THE QUESTION THEN BECOMES
ARE THESE MAKO PAGES
IMPORTANT IN THE RAPID
IMPROVEMENT OF THE CD8 T
CELLS.
YOU CAN DELETE THE
MONOCYTES, THE MACROPHAGES
AND AS WELL AS THE MAKO
PAGES USING INTRAASAL WITH
THE ADMINISTRATION.
AND WHAT WE SAW WAS THAT
WHEN HE WE DEPLETE THIS
MACRO PAGES THE ENHANCED
CLEARANCE AS WELL AS THE
CD8 CELL RESPONSE WE SEE
IN MICE PREVIOUSLY.
BECOME ABROGATED.
SO WHAT I'VE SHOWN TOLD
YOU TODAY IS THAT HELMINTH
INFECTION LEADS TO A
CHANGE IN MACROPHAGE
PROFILE AND THIS
MACROPHAGE IS IMPORTANT IN
VIRAL CLEARANCE SO I JUST
WANTED TO MENTION THAT ALL
THOSE HAVE EVEN THIS WITH
OTHER HELMINTH THIS IS A
QUESTION WE GET WHICH IS
ANOTHER HELMINTH THAT IS
PRESENT IN THOSE REGIONS
THAT I MENTIONED.
THEY ALSO SEE THAT THERE
IS ENHANCED CD8 SO THAT
HELPFUL IN VIRAL
INFECTION.
SO INCLUSION, PRIOR
HELMINTH INFECTION IS IN
THE LUNG AND THIS IS
IMPORTANT IN ENHANCING THE
CD8 RESPONSE AND VIRAL
RESPONSE WITH
SARS-CoV-2.
TO SUM UP AND GIVE YOU AN
OVER VOW OF WHAT WE ARE
INTERESTED IN, ALL OF
THESE STUDIES HAVE SHOWN
IS THEN BEGINNING TO SHOW
SHA HELP MINUTE INFECTION
OR AN INDIVIDUAL IN
ENVIRONMENTS IS IMPORTANT
IN THE TIMING HEALTH
CONTINUING INFECTION AND
WHAT WE'LL DO IN OUR
UNIQUE UNITS IS BEGIN TO
STUDY HOW HELMINTH
INFECTION CAN REPROGRAM
THE IMMUNE SYSTEM AND THEN
HOW THAT CAN THEN
INFLUENCE HOW ORDER AND
SOULS EITHER VIRUSES OR
FUNGI INFECTIONS.
AND WITH THAT OUR TIME
COMES ALL MY COLLEAGUES IN
THE SECTION AND MY PI AND
LUCAS AND KELSEY IN NEW
RECRUITS FOR THE
INDEPENDENT AWARD AND WITH
THAT I SAY THANK YOU AND
ANY QUESTIONS THAT YOU
WOULD HAVE.
>>I DO HAVE A QUESTION
FROM ON-LINE.
AND I HAVE ONE TOO.
CAN THE SEX OF THE MICE
MAKE ANY DIFFERENCE.
>>NO.
NOT IN THIS CASE.
>>AND MY QUESTION, IF I
CAN REMEMBER IT, THE
SLIDES ARE GONE.
ARE THERE AREAS OF -- ARE
THERE REGIONS THAT ARE
ENDEMIC WITH THIS KIND OF
INFECTION?
DID THEY HAVE LOWER RATES
OF COVID.
DO WE HAVE EPIDEMIOLOGICAL
DATA TO SUPPORT THAT MIGHT
HAVE HELPED PREVENT THE
SPREAD OF HUMAN COVID?
>>YEAH.
THANK YOU.
LIKE I MENTIONED WHEN I
STARTED, THERE IS ONE
STUDY FROM' TOPIA THAT
MIGHT BE CORRELATION
BETWEEN HELMINTH INFECTION
AND EPIDEMIOLOGICALLY YES.
THE MORTALITY TO
SARS-CoV-2 IS KIND OF TO
SARS-CoV-2 IS LOWER IN
REGIONS WHERE THERE ARE
INFECTION.
>>AMAZING.
>>I'M WONDERING IF THERE
IS EVIDENCE THAT THIS IS
SPECIFIC TO HELMINTH
INFECTION OR WHETHER THERE
ARE EITHER ENVIRONMENTAL
OR OTHER INFECTIOUS
FACTORS THAT CO SEGREGATE
IN THESE REGIONS?
>>GREAT QUESTION.
SO YEAH, WHETHER THE
ENVIRONMENT MATTERS OR
IT'S HELMINTH INFECTION IN
PARTICULAR.
WE HAVE THIS MODEL WE'RE
COLLABORATING WITH ANDREA
GRAHAM WHERE WE TAKE MICE
INTO A ENVIRONMENT TO KIND
OF DISTORT HOW DOES THE
ENVIRONMENTS REALLY PLAY A
ROLE IN OUTCOMES TO
SARS-CoV-2 OR OTHER
VIRAL SO USING THAT MODEL
WE WILL BE ABLE TO ANSWER
THAT QUESTION.
WE DON'T HAVE AN ANSWER
YET BUT YEAH.
THANK YOU, VERY MUCH.
[APPLAUSE]
>> Parinaz Fathi: SO NEXT
WE'LL HAVE Dr. SHAUN
ABRAMS PART OF THE 2023
INDEPENDENT REOPEN SCHOLAR
COHORT AND HE IS LEADING
THE CRANIO FACIAL
DEVELOPMENT IN THE
NATIONAL INSTITUTE OF
DENTAL AND RAIN YO FACIAL
RESEARCH AND HE COMPLETED
HIS PH.D IN THE ORAL AND
SCIENCE GREAT WAD PROGRAM
AT UNIVERSITY OF
CALIFORNIA SAN FRANCISCO.
[APPLAUSE]
PLEASE WELCOME OUR
SPEAKER.
>>GOOD MORNING.
THANK YOU SO MUCH TO THE
ORGANIZERS FOR THE
OPPORTUNITY TO PRESENT MY
PRELIMINARY WORK AND I'M
REALLY EXCITED TO PRESENT
IT IN THIS EARLY STAGE
BECAUSE IT'S A PROJECT
THAT CAME FROM A REALLY
EXCITING, USUAL FINDING
THAT CAME FROM MY PH.D
WORK AT THE UNIVERSITY OF
CALIFORNIA SAN FRANCISCO
THAT I'M EXCITED TO
SPEARHEAD TACKLING
INDEPENDENTLY AS AN IRS
SCHOLAR.
I'M ALSO REALLY GRATEFUL
FOR MY CO PRIMARY MENTORS
WHO HAVE BOTH ALLOWED ME
TO DRIVE THIS PROJECT
INDEPENDENTLY IN ADDITION
TO A COLLABORATIVE PROJECT
I'M RUNNING BETWEEN THEIR
TWO LABS.
AND THIS PROJECT STEMS
FROM UNDERSTANDING HOW
SCENERY OWLS WHICH ARE --
WE'VE UNDISCOVERED TISSUE
SPECIFIC REQUIREMENT FOR
THIS ORGANEL AND FACIAL
VEM.
THE PROJECT STEMMED FROM
AN INTERESTING FINDING
WHERE TWO HUMAN DISORDERS
THAT ARE CAUSED BY
MUTATIONS IN THE SAME GENE
CAN EFFECT DIFFERENT
ORGANS AND TISSUES.
SO THE FIRST CASE YOU HAVE
PRIMARY MICROCEPHALY WHICH
IS RECESSIVE DISORDER
WHICH PRIMARILY EFFECTS
DEVELOPMENT OF THE BRAIN
AND PRESENTS WITH
DRAMATICALLY REDUCES BRAIN
SIZE AT BIRTH AND
CONTINUING THROUGHOUT THE
DEVELOPMENT.
AND YOU CAN SEE THAT IN
THIS INDIVIDUAL HERE.
IN ADDITION, WE HAVE
ANOTHER RARE DISORDER
SECEL SYNDROME CAUSED BY
MUTATION IN THE SAME GENE
THAT IN ADDITION TO
MICROCEPHALY AND
DRAMATICALLY REDUCED BRAIN
SIZE THIS SYNDROME
PRESENTS WITH A GLOBAL
DEFECT IN OVER ALL GROWTH
OR DWARFISM AS WELL AS THE
PRESENCE OF CRANIO FACIAL
DEFECTS.
SUCH AS RETRO NAPPIA OR
THE LOWER JAW TOO FAR BACK
AS WELL AS MICRO WHICH
PRESENTS HAS A HIGH OWE
PLASTIC OR SMALL JAW.
SO BOTH OF THESE DISORDERS
CAN BE CAUSED BY MUTATIONS
IN SEM PJ KNOWN AS PROTEIN
J AND SAS34 OR CPAC AND IN
THE FLY, THEY FOUND THAT
CENPJ OR SAS-4 YOU CAN SEE
IT CO LOCALIZES WITH GAMMA
TUBE YOU LYNN IN THE FINE
NEURO BLAST AND WHEN YOU
KNOCK OUT SAS-4, YOU LOSE
SENTRY OWLS IN THE FLY.
SO FIRST THEY FORM THE CO
COMPONENT OF THE
ORGANIZING CENTER AND IT'S
CRITICAL FOR ANCHORING
SPINDLE MICRO TUBE Y'ALL
DURING CELL DIVISION AND
LATER ON, THESE CENTRIOLES
WILL GO ON TO FORM THE
BASIL BODY THAT WILL
TEMPLATE FORMATION OF
SILLY A WHICH WE HAVE COME
TO APPRECIATE TO BE
IMPORTANT FOR HUMAN
DEVELOPMENT BECAUSE IT CAN
LEAD TO A WHOLE CLASS OF
DISORDERS KNOWN AS SILLY
OTH A PEES.
SO THERE'S BEEN SOME
MOUNTING EVIDENCE THAT
CHARGES THE DOGMA THAT
CENTRIOLES ARE REQUIRED
FOR CELL DIVISION.
THERE'S A SEMINOLE PAPER
IN 2006 WHERE THEY KNOCKED
OUT SASS-4 OR CENPY AND
WHEN YOU COMPARE THEM HERE
THEY WERE PRETTY SIMILAR
TO WILD TYPE COUNTERPARTS.
AND INDICATING THAT
CENTRIOLES MAY NOT BE AS
CRITICAL FOR CELL DIVISION
AS WE THINK.
IT'S THE SAME TRUE FOR
SYSTEMS BUT IN THE MOUSE
THEY DID A SIMILAR
DESELECTION OF SASS-4 IN
THE MOUSE THAT MUTATION
LED TO APPROXIMATE
MEDICINE GESTATION.
THEY WERE REQUIRED FOR
DEVELOPMENT IN THE MOUSE.
WHEN THEY LOOKED AT MOUSE
TISSUE THEY FOUND 24 IN
THESE MUTE OUNCE THEY LED
TO WE HAD PRIDED CELL DECK
WITHIN THE EMBRYO LEADING
TO THAT LETHALITY.
THE CENTRAL QUESTION HERE
IS HOW DOES CENTRIOLES
LOSS CAUSE HUMAN DISEASES
WITH PHENOTYPES DISTRICTED
TO ORGANS.
IN MICROCEPHALY, IT'S
RESTRICTED TO THE
DEVELOPING BRAIN.
FIRST IN ADDITION TO THE
BRAIN DEFECTS WE ALSO HAVE
THE PRESENCE OF CRANIO
FACIAL ABNORMALITIES AS
WELL AS OVER ALL GROWTH
DEFECTS.
AND TO TACKLE THIS, WE USE
A CONDITIONAL KNOCK OUT
APPROACH BECAUSE GLOBAL
KNOCK OUT IS LETHAL IN THE
MOUSE AND IN MY FIRST
INVESTIGATION I LOOKED AT
KNOCKING OUT THIS PROTEIN
IN RAPIDLY DIVIDING AND A
DETERMINAL ORGAN USING THE
SONIC HEDGE HOCKEY DRIVER
THAT WILL COMPARE ME LOSS
OF SENTRY OLE IN THE LUNG
AND THE INTESTINE AND NOW
I'M INTERESTED IN LOOKING
AT THE REQUIRE MANIES FOR
CENTRIOLES SPECIFICALLY IN
THE CRANIO FACIAL COMPLEX
AND I'VE BEEN USING THE
SOX NINE FREE DRIVER THAT
KNOCKS OUT THIS PROTEIN
AND CRANIO FACIAL TISSUES.
FIRST THE CONSEQUENCE OF
LOSING CENPJ.
YOU ARE LOOKING AT I 16.5
MOUSE LUNG AND YOU CAN SEE
IN THE BRIGHT FIELD IMAGE
WE HAVE A BEAUTIFUL LUNG
STRUCTURE HERE AND IN OUR
RED SIGNAL YOU CAN SEE
WHERE WE HAVE ACTIVATION
OF THAT SONIC HEDGEHOG IN
THE LUNG EPIDEMIOLOGY YUM
AND THIS IS OUR CONTROL
MODEL.
IF WE KNOCK OUT USING THIS
CREE DRIVER WE SEE A
DRAMATIC IMPAIRMENT IN
DEVELOPMENT OF THE LUNGS
SO YOU CAN SEE COMPARED TO
THE WILD TYPE LUNG YOU
HAVE A DRAMATICALLY
IMPAIRED OR HYPO PLASTIC
LUNG WHICH HAS NOT
COMPLETED BRANCHING TO
DEVELOP INTO THE ORGAN.
IT'S THE SAME TRUE IF WE
LOOK IN THE GUT.
SO THIS IS TELLING US THAT
CENTRIOLES ARE REQUIRED
FOR DEVELOPMENT OF THE
LUNG.
WHEN I LOOKED AT THE GUT,
I SAW SOMETHING REALLY
SURPRISING.
SO ON THE TOP PANEL HERE,
YOU HAVE AN EMBREE ON A
DAY 16.5 INTESTINE AND YOU
CAN SEE IN RED RTD TOMATO
SHOWING WHERE OUR CREE IS
ACTIVE AND WE OPEN UP THE
GUT AND MEASURE THE
CONTROL VERSUS THE MUTANTS
I SAW THERE WAS NO
DECREASE IN THE
DEVELOPMENT OF THE GUT
WHEN WE DELETE CENTRIOLES
SO THIS STARTED TO UNCOVER
THE FACT THAT CENTRIOLES
ARE REQUIRED IN SOME
TISSUE SUCH AS THE LUNG
BUT ARE DISPENSE ABLE IN
OTHER TISSUES SUCH AS THE
GUT.
SO JUST TO REMIND YOU THIS
IS THE CONTROL LUNG AND
THIS IS OUR MUTANT LUNG
WHERE WE HAVE DRAMATICALLY
IMPAIRED LUNG DEVELOPMENT
AND IF WE TAKE THIS SAME
MUTANT AND DELETE P53 WE
CAN RESTORE DEVELOPMENT OF
THE LUNG REALLY
HIGHLIGHTING THAT IT'S
REALLY A P53 MECHANISM
THAT'S LEADING TO THE CELL
DEATH AND IMPAIRED ORGAN
DEVELOPMENT.
SO AS A CRANIO FACIAL
DEVELOPMENT BIOLOGIST I'M
REALLY INTERESTED IN
MOVING THIS WORK FROM THE
GUT AND THE LUNG INTO THE
CRANIO FACIAL COMPLEX.
AND THIS IS USING SOCKS
DEGREE RIVER THAT WILL
ALLOW ME TO DELETE CENPJ
IN VARIOUS CRANIAL TISSUE.
AND THEN SOX 9 IS LATER IN
THE THAT WILL GIVE RISE TO
CARTILAGE AND CON DRO
SIGHTS.
A LITTLE BIT OF
BACKGROUND.
IT'S A STEM CELL
POPULATION CRITICAL FOR
DEVELOPMENT OF THE CRANIO
DEVELOPMENT COMPLEX SO THE
NEURO CREST STARTS TO
DEVELOP TOWARDS THE END OF
GUEST RELATION.
AT THE NEURO PLATE BORDER
THE JUNK TUN BETWEEN THE
DEVELOPING NEURO PLATE
THAT GOES ON TO FORM THE
CENTRAL NERVOUS SYSTEM AND
GOING ON TO FORM THE SKIN.
WHEN THE NEURAL TUBE
FOLDS, THE NEURO CREST
CELLS LIE DORSAL ASPECT
AND UNDERGO A TRANSITION
TO MIGRATE TO A VARIOUS
DISTINCT AREA THROUGHOUT
THE EMBRYO TO GIVE RISE TO
A VARIETY OF DIFFERENT
CELL TYPES.
THESE INCLUDE PERIPHERAL
NERVOUS SYSTEM, AND THE
STRUCTURE THAT I'M REALLY
INTERESTED IN AND THE RAIN
YO FACIAL SKELETON.
SO JUST A LITTLE BIT OF
BACKGROUND ON O CRANIAL IN
HUMANS THIS IS A
BEAUTIFULLY ELEGANT
PROCESS WHEREBY YOU HAVE A
VARIETY OF DIFFERENT
FACIAL PRIME MOR TEE A YOU
HAVE YOUR LATERAL NASAL
PROM INNSANCE, AND
MANDIBULAR PROM INNSANCE
THAT GROW, FUSE AND SIGNAL
TO ONE ANOTHER IN ORDER TO
FORM A FINAL FACIAL FORUM
THAT IS FREE FROM DEFECTS
AND WE KNOW PROLIFERATION
OR SIGNALING BETWEEN THESE
DIFFERENT TISSUE TYPES
LEAD TO CRANIO FACIAL
DEFECTS WHICH OCCUR IN THE
ONE-THIRD OF ALL BIRTH
DEFECTS.
AND THE MOUSE MODEL
BECAUSE OF ITS SIMILARITY
IN THE SIGNALING PATHWAYS
THAT GUIDE FACIAL
DEVELOPMENT IN THE MOUSE
AND THE HUMAN, AND THE
DEVELOPMENT WHEREBY THERE
ARE STAGES BETWEEN THE
EMBRYONIC DEVELOPMENT OF
THE MOUSE AND THE HUMANS
THAT ARE VERY SIMILAR THAT
ALLOWS THIS TO BE A GREAT
MODEL TO UNDERSTAND THE
SIGNALING MECHANISMS
GUIDING CRANIO FACIAL
DEVELOPMENT.
SO WHEN WE LOOKED AT
KNOCKING OUT SOX 9 FREE
DRIVER AT 'EM DEGREE ON I
CAN DAY 16.5 YOU CAN SEE
THE FRONTAL AND LATERAL
VIEWS OF THIS MOUSE EMBRYO
AND COMPARED TO THIS
CONTROL EMBRYO, WHEN WE
LOSE CENTRIOLES, WE SEE A
NUMBER OF SEVERE CRANIO
FACIAL DEFECTS.
SO WE SEE A MID LINE
CLEFT, AND IN THE SIDE
VIEW YOU CAN SEE A
DRAMATICALLY ABSENT
MAXILLA THAT FORM THE
UPPER JAY AND THE MAN DA
DEBULL SO WE HAVE
INCREASED MID LINE WIDTH
BETWEEN OUR MUTANTS AND
CONTROLS AND FACIAL CLEFT
AND THEY ARE REMINISCENT
OF THE CLINICAL FEE SUES
OF SECEL SYNDROME.
IF WE LOOK TWO DAYS
EARLIER AT DAY 14.5 WE SEE
THESE DEFECTS ARE ALREADY
APPARENT SO SHOWING THAT
THIS IS HAPPENING DURING
EARLY EMBRYONIC
DEVELOPMENT.
AND I WAS VERY FORTUNATE
TO HAVE A VERY TALENTED
MRSP STUDENT, KAITLYN
FOSTER, WHO WORKED WITH ME
GETTING THIS PROJECT OFF
THE GROUND FOR THE PAST
YEAR.
SO FIRST WE WANTED DO A
PLASTIC DEVELOPMENTAL
BIOLOGY APPROACH BY
LOOKING EARLY ON DURING
EMBRYONIC DEVELOPMENT TO
TRY TO PINPOINT WHEN THESE
DEFECTS FIRST HAPPENED
DURING CRANIO FACIAL
DEVELOPMENT AND IN WHAT
CELL TYPES THESE DEFECTS
ARE FIRST OCCURRING.
SO FIRST WE MEASURED THE
MID LINE WIDTH OF THESE
EMBRYOS AT EMBRYONIC DAY
10.5 AND AS A PROXY WE
MEASURED THE DISTANCE
BETWEEN THE NASAL PITS OF
THE MOUSE AM BRIOUX IN
THIS FRONTAL VIEW.
WHEN WE COMPARED CONTROL
AND CONTINUAL KNOCK OUT
MUTANTS, YOU CAN SEE THAT
THERE'S SOME MILD DEFECTS
BUT IT DOESN'T LOOK LIKE
THERE'S A SIGNIFICANT
INCREASE OR DECREASE IN
MID LINE FACIAL WIDTH.
IF WE LOOK ONE DAY FURTHER
WE CAN SEE CLEAR DEFECTS
AND WE MEASURE THE FACIAL
MID LINE WIDTH WE SEE
THERE'S A WIDENING THE
FACIAL MID LINE IN OUR
CONTINUAL KNOCK OUTS AND
THIS IS EVEN MORE SEVERE
WHEN WE LOOK AT EMBRYONIC
DAY 12.5.
AT THIS POINT YOU HAVE NO
UPPER OR LOWER JAW AND YOU
HAVE A DRAMATICS EXPANSION
OF THE MID LINE IN THESE
MUTANTS.
IT'S SHOWING THAT WE DON'T
SEE ANY DEFECTS IN MID
FACE WITH AT 10.5 AND WE
GET A PROGRESSIVE INCREASE
IN THAT MID LINE WIDTH
MEASUREMENT AS WE PROGRESS
THROUGH DEVELOPMENT.
LOOKING AT WHETHER CELL
DEATH INCREASE CELL DEATH
IS DRIVING THE APPEARANCE
OF THIS PHENOTYPE.
WE LOOKED AT CELL DEATH
FIRST PRIMARILY LOOKING AT
IN THE JAW SO THIS IS THE
FIRST ARCH LOOKING AT THE
MANDIBULAR PROVE I AMANCE
THAT GIVE RISE TO THE
LOWER JAW AND WE SEE A
DRAMATIC INCREASE IN A
INCREASE IN CELL DEATH IN
THE LOWER LAWYER DURING
THAT IS ALREADY APPARENT
AT EMBRYONIC DAY AT 10.5
BEFORE I SAW ANY OVERT
DEFECT IN THE FACIAL MID
LINE DEVELOP MANY.
IF WE LOOK LATER AND THE
LOSSES OF ON THE
DEVELOPMENT, THIS IS AN
EMBRYONIC 6.25 LATERAL
MOUSE THAT WE HAVE DONE TO
LOOK AT THE 12 THE
CARTILAGE IN BLUE AND WHEN
WE COMPARE TO THE CONTROLS
WE SEE IN OUR MUTANTS AND
WE HAVE A DRAMATIC
IMPAIRMENT IN DEVELOPMENT
OF BOTH THE BONE AND CARD
LIGE IN OUR MUTANTS SO YOU
HAVE BASIC FLEE MAX OR
UPPER JAW OR LOWER JAW,
LOSS OF CARTILAGE AND
SEVERE DEFECTS IN SKULL
DEVELOPMENT.
SO I POINTED IN THE LUNG
AND TOTE KNOCK OUT AND
SHOWED P53 WAS ESSENTIAL
MEET EIGHT OR IN THIS
FORMATION OF THESE DEFECTS
AND WE WANTED TO ALSO LOOK
AT WHEN WE CAN RESCUE
THESE BY DELETING P53 IN
THIS NEW MODEL THAT I'VE
DEVELOPED AND JUST TO
REMIND YOU AGAIN OF THESE
DEFECTS, THIS IS EMBRYONIC
DAY 17.5 CONTROL EMBRYOS
IN THE FRONTAL AND LATERAL
VIEW AND THIS IS OUR
CONDITIONAL MUTANTS WHERE
WE CAN SEE THAT MID LINE
FACIAL CLEFT AND A
DRAMATICALLY HYPO PLASTIC
OR ABSENT MAXILLA AND MAN
DA BELL AND YOU TAKE THE
SAME MUTANT AND DELETE P53
WE CAN DRAMATICALLY
RESTORE NORMAL DEVELOPMENT
OF THE CRANIO FACIAL
COMPLEX RESTORING
DEVELOPMENT OF THE UPPER
AND LOWER JAW AND
PREVENTING THE DEVELOPMENT
OF THAT MID LINE FACIAL
CLEFT.
SO THIS IS REALLY EXCITING
FOR US TO START OUT THE
PROJECT HERE AT THIS POINT
BECAUSE THERE'S SO MANY
EXCITING AVENUES THAT WE
WANT TO MOVE INTO FROM
THESE EARLY RESULTS.
AND JUST TO SUMMARIZE WHAT
I'VE SHOWN YOU SO FAR
TODAY, I'VE SHOWN YOU THAT
LOSS CENTRIOLES THEY CAN
CAUSE TWO DISTINCT HUMAN
DISEASE, MICROCEPHALY WITH
DEFECTS IF BRAIN
DEVELOPMENT AND SECKLE
SYNDROME AND SIN TREE OWLS
ARE REQUIRED FOR THE
DEVELOPMENT OF SOME ORGANS
SUCH AS THE LUNG IN THE
MOUSE BUT DISPENSE ABLE
FOR THE DEVELOPMENT OF
OTHERS SUCH AS THE BUT
THE.
AND OUR PRELIMINARY
ANALYSIS OF THE CRANIO
FACIAL DEFECTS SHOW THAT
THE CENPJ MODEL DOES PINOT
COPY SOME ASPECTS OF SECEL
SYNDROME AND WE'VE SHOWN
THAT P53 DELETION CAN
RESCUE THE DEFECTS WE SEE
IN THIS M PJ CONDITION AT
KNOCK OUT SO WITH THIS I
AM EXCITED AND OVER THE
NEXT THREE YEARS AND AS AN
IRS SCHOLAR TO ELUCIDATE
THE MECHANISM THAT IS
UNDERLINED THE CRANIO
FACIAL DEFECTS IN OUR
KNOCK OUT MODEL AND OUR
PINOT TIP I CAN RESCUE
WITH P53 SO WE'RE EXCITE
TODAY DO MORE
CHARACTERIZATIONS AND
REALLY IDENTIFY THE ONSET
IN CELLULAR MECHANISMS
THAT ARE DRIVING THE
DEVELOPMENT OF THESE
CRANIO FACIAL DEFECTS AND
I'M EXCITED THAT USING OUR
MOUSE GENETICS SYSTEM WE
HAVE A NUMBER OF TOOLS
THAT WILL ALLOW US TO
DELETE THIS MPJ IN A LOT
OF THE DIFFERENT CELL
TYPES TO FORM THE CRANIO
FACIAL COMPLEX SO WE CAN
KNOCK OUT IN THE NEURAL
CREST AND KNOCK IT OUT IN
THE SURFACE THAT FORMS THE
SKIN AND THE BRAIN AS WELL
AS IN THE CRANIO FACIAL
MISO DERM SO I'M EXCITE
TODAY UNCOVER WHICH CELL
TYPES ARE SUSCEPTIBLE TO
LOSS OF CENTRIOLES AND
WHICH ARE NOT AND TO
IDENTIFY PROTECTED
MECHANISM THAT'S ALLOW
CERTAIN CELL TYPES WITHIN
THE CRANIO FACIAL COMPLEX
TO DEVELOP IN THE ABSENCE
OF CENTRIOLES AND THEN AS
I MENTIONED, ALSO
INFORMING SILLIA AND NOW
WE HAVE THE TOOLS TO
DISSECT THE FUNCTIONS OF
CENTRIOLES AND CENPJ IN
THE ROLE FOR THEIR
FUNCTION IN CELL DIVISION
SEPARATELY FROM THEIR
FUNCTION IN SILLY A
FORMATION BECAUSE WE CAN
GENETICALLY DELETE SILLY A
USING A IFT88 KNOCK
OUTCOME PAIRED THAT TO OUR
CENPJ KNOCK OUT AND WHAT
IS REGULATE TODAY IDENTIFY
ZEALIA INDEPENDENT
REGULATION OF CENPJ AND
I'M EXCITED HERE TO
DEVELOP HUMAN IPC MODELS
OF SECEL SYNDROME AND I
HAVE A COLLABORATOR WHO
HAS A COHORT OF SECEL
PATIENTS AND IPSCs THAT
EXIST SO I'M EXCITED TO
USE THAT AS A MODEL TO GET
AT MECHANISM AS WELL AND
IN ADDITION TO CREATING A
HUMANIZED MOUSE MODEL
WHERE I CAN MAKE THE EXACT
CENPJ IN A MOUSE MODEL AND
FINALLY AS A SENTIST
SCIENTIST AND CLINICIAN
SCIENTIST I'M EXCITED TO
BE HERE WHERE I CAN DO
CRANIO FACIAL PHENOTYPING
AND COLLABORATE TO DO SOME
PHENOTYPING OF SICKEL
SYNDROME PATIENTS AT NIH
AND THE DENTAL CLINIC AND
WITH THAT I WOULD LIKE TO
THANK MY PH.D MENTOR
JEREMY RIDER THE UCSF WHO
ALLOWED ME TO TAKE THIS
WITH ME TO SPEARHEAD AND
DRIVE INDEPENDENTLY HERE.
I'M GRATEFUL FOR MY CO
PRIMARY MENTORS HERE AT
NIDCR WHO HAVE BEEN REALLY
AMAZING AT ALLOWING ME TO
DRIVE THIS PROJECT IN
ADDITION TO THE PROJECT
I'M RUNNING IN
COLLABORATION WITH THE TWO
LABS AND AIM GRATEFUL AND
DIRECTOR LEADERSHIP
MATTHEW HOFMANN THE PAST
SCIENTIFIC DIRECTOR WHO
NOMINATED ME FOR THIS
PROGRAM AND WHO WAS AN
INCREDIBLE MENTOR FOR ME
WHO I WAS POSTBAC AND TO
BE BACK AT NIDC RESEARCH
SCHOLAR IS SPECIAL FOR ME
AND I'M GREATING FOR THE
NIDCR CLINICAL RESEARCH
FELLOWSHIP PROGRAM AND
EXCEPTIONAL STUDENT
KAITLYN FOSTER WHO I WAS
FORTUNATE TO HAVE THE
OPPORTUNITY TO MENTOR OVER
THE PAST YEAR AND I'M
REALLY EXCITED TO WELCOME
TWO NEW MEMBERS OF THE
CRANIO FACIAL DEVELOPMENT
UNIT BIANCA AND DAY
GENTLEMAN AND I'M EXCITED
THAT YOU ARE JOINING ME ON
THIS QUEST TO LOOK AT THE
ROLE OF CENTRIOLES AND
CRANIAL FACIAL
DEVELOPMENT.
WITH THAT I'M EXCITED TO
TAKE ANY QUESTIONS.
>>NO QUESTIONS ON-LINE.
BIANCA, EVERY DAY WE DON'T
HAVE FOOD ALL OVER THE
PLACE AT THE NIH BUT TODAY
WE DON'T.
>>SO WITH REGARD TO THE
CELL DEATH THAT IS
OBSERVED IN
TISSUE-SPECIFIC MANNER,
THE INTESTINES ARE FAIRLY
RESISTANT TO P53 WHETHER
IT'S THROUGH A RADIATION
OR UV EXPOSURE AND DO YOU
THINK THAT THE TISSUE
SPECIFICITY ARISES FROM A
RESISTANCE THAT IS
SPECIFIC OR ARE THERE
OTHER MECHANISM THIS IS
OTHER TISSUES?
>>THAT'S A GREAT
QUESTION.
IN THE GUT AND LUNG STORY,
WE ACTUALLY FOUND THAT
REGIONS OF SIGNAL -- AND I
DIDN'T SHOW THE DATA BUT
IN THE LING, THERE WERE
ACTUALLY TWO DIFFERENT
POPULATIONS SO YOU HAVE
THIS SOX 2 POSITIVE
PROXIMAL THAT DOESN'T HAVE
SIGNAL NORTH THE VICINITY
AND YOU HAVE MORE DISTAL
SOX 9 POSITIVE THAT HAS
ACTIVITY AT THE DISTAL END
BUDS AND IN THAT MUTANT
LUNG YOU ONLY HAVE AN
EXPANSION OF THE SOX 9 AND
WE THINK THAT IT'S A
PROJECT TIVE IRK SIGNALING
THAT ALLOWS THAT CELL TYPE
TO SURVIVE AND THE OTHER
PROXIMAL TO BE MORE
SENTRIAL SO GREAT QUESTION
AND I'M EXCITED TO SEE IF
THOSE MECHANISMS ARE ALSO
AT PLAY OR IF THEY'RE NEW
MECHANICKISTS THAT ALLOW
THESE CELLS TO DEVELOP IN
THE ABSENCE OF
CENTRIOLES.
>>I HAVE A QUESTION THAT
JUST CAME IN.
SOMEONE IS ASKING WHETHER
YOU SEE NEW WAYS TO TREAT
NEW PATIENTS.
>>THAT'S A GREAT
QUESTION.
SO P53 IS NOT A TARGET WE
WRITE.
IT'S A TIME OR SUPPRESS OR
AND WE DO WANT TO MESS
WITH P53 BUT WE -- THERE'S
A LOT OF RECENT WORK
THAT'S IDENTIFIED WHAT IS
UPSTREAM OF P53
ACTIVATION.
AND THERE'S ACTUALLY A U
SP28 WHEN THEY KNOCK THAT
OUT THEY CAN RESCUE THE
CELL DEATH THAT THEY SEE
IN THE BRAIN SO I'M
INTERESTING TO SEE IF
THERE ARE BETTER TAG HE ET
CETERA UPSTREAM THAT MIGHT
BE INTERESTING CLINICAL
TARGETS IN THE FUTURE SO
THAT'S A GREAT QUESTION.
>>I'M CURIOUS WHAT
HAPPENS ON THE CHROMOSOME
LEVEL WITH THE CENTRIOLES
IF?
HOW DO THEY GET TO AND HOW
DO THEY DIVIDE AND WHAT
HAPPENS WITH THE
CHROMOSOMAL STABILITY?
WE HAVEN'T LOOKED AT THE
MOUSE IN OUR GUT KNOCK
OUT.
THERE AOR GROUPS THAT HAVE
SHOWN THAT DNA DAMAGE
RESPONSE PATHWAYS THERE'S
INCREASE IN GAMMA HTAX SO
THERE'S SOME DATA SHOWING
THAT THERE IS INCREASED
DNA DAMAGE AND WITH
BIPOLAR SPIN DAL FORMATION
BUT IT SEEMS TOCK CELL AND
ORGANISMS CONTEXT
DEPENDENT.
BUT WE HAVEN'T, IT WOULD
BE INTERESTING TO LOOK AT
THAT IN OUR MOUSE MODEL
WHEN WE GET MORE DETAILED
INTO THE MECHANISM BUT
IT'S A GREAT QUESTION.
>>THANK YOU.
[APPLAUSE]
AND THE LAST PEAKER IS
MARY DIAZ SAN TAN A. PART
OF THE 202 COHORT AND IS
PART OF THE NATIONAL
INSTITUTE OF ENVIRONMENTAL
HEALTH SCIENCES.
SHE COMPLETED HER PH.D IN
EPIDEMIOLOGY THE THE
UNIVERSITY OF
MASSACHUSETTS AMHERST.
>>GOOD MORNING, EVERYONE.
MY NAME IS MARY DIAZ
SANTANA AND IMPART OF THE
2022 IRS COHORT AND THE
DATA FOR MY PRESENTATION
TODAY IS PERSONALIZED RISK
PREDICTION MODELS FOR
BREAST CANCER IN HISPANIC
WOMEN.
THE IMPORTANCE OF
CONSIDERING HISPANIC
SUBGROUPS AND THE SOCIAL
ENVIRONMENT.
ONE OF THE LONG-TERM
RESEARCH GOALS OF MINE IS
TO LESSEN THE BURDEN OF
BREAST CANCER AND RACIAL
MINORITY WOMEN ESPECIALLY
HISPANIC WOMEN TO
PRECISION PREVENTION.
MY PROPOSED RESEARCH IS A
AN EXTENSION OF MY
GRADUATE AND POSTDOCTORAL
TRAINING WITH SOCIAL EARLY
LIFE FACTORS, IS
ENVIRONMENTAL FACTORS AND
THE RELATIONSHIP WITH
BREAST CANCER RISK.
NOW THAT I HAVE
TRANSITIONED INTO THIS
INDEPENDENT POSITION, I AM
TAKING MY RESEARCH FOCUS
INTO A SLIGHTLY NEW
DIRECTION UNDER THE
GUIDANCE OF MY MENTORSHIP
TEAM AND I'M ESTABLISHING
PROGRAMS FOCUSED ON
REDUCING HEALTH
DISPARITIES, ESPECIALLY IN
BREAST CANCER RELATED BY
INTEGRATING THE USE EVER
BIOLOGICAL BEHAVIORAL
SOCIAL ECONOMIC AND
EPIDEMIOLOGIC DATA.
ALL OF THESE ARE
COMPONENTS OF A PRECISION
PREVENTION.
IN THE CASE OF THE CURRENT
PROJECT, SORRY, THAT I AM
WORKING ON AND THAT I WILL
DISCUSSING WITH YOU TODAY,
THE END GOAL OF THIS
PRODUCT IS TO REDUCE THE
BURDEN OF BREAST CANCER
AMONG HIS PANIC WOMEN
SPECIFICALLY.
"WOULD LIKE TO APPROXIMATE
DESCRIBE THE POPULATION I
AIM TO FOCUS ON IN THIS
POPULATION.
THE HISPANIC POPULATION IS
THE SECOND LARGEST RACIAL
ETHNIC GROUP IN THE UNITED
STATES AFTER NON-HISPANIC
WHITES IN OVER ALL.
APPROXIMATELY 60 MILLION
HISPANICS LIVE IN THE
CONTINENTAL U.S. IN 2019
COMPARED TO 18% OF THE
ENTIRE POPULATION.
THAT HISPANIC IS USING
WITH LATINO, LATINA, LATIN
X BUT WHO ARE HISS PAN
PICK AND LATINO AND THE
TERM HISPANIC WHEN USED AS
AN OBJECTIVE MEANS
RELATING TO SPAIN, AS A
NUMBER IT'S SPECIFICALLY
REFERS TO SPANISH-SPEAKING
PERSON LIVING IN THE U.S.
OR CANADA OR A PERSON WHO
IS FAMILY CAME FROM A
SPANISH-SPEAKING COUNTRY.
LATINO OR LATINA IS A
PERSON WHO COMES FROM
LATIN AMERICA OR WHOSE
FAMILY CAME FROM A LATIN
AMERICA COUNTRY AND FAMILY
LANGUAGE IS A EITHER
SPANISH, FRENCH, OR
PORTUGUESE.
AS YOU CAN SEE IN THIS
DIAGRAM, THE MINORITY FALL
IN THE MIDDLE OF THE
DIAGRAM AND THEY'RE ALSO
LATINO BUT THE SAME IS NOT
NECESSARILY TRUE IN
REVERSE AND FOR THE
PURPOSE OF THIS
PRESENTATION, WE'LL BE
TALKING ABOUT PEOPLE IN
THIS MILLION DOLLAR OF THE
DIAGRAM.
HISPANIC SHARE A COM AN
LANGUAGE IN SPANISH AND
COME FROM LATIN AMERICA AS
I JUST MENTIONED.
THEY CAN BE AS CULTURALLY
AND BIOLOGICALLY AND
PHENOTYPICALLY FROM ONE
ANOTHER TWO ANY OTHER TWO
INDIVIDUALS FROM ANY OTHER
ETHNICITY.
IT DEFINES RACE AS
DISTINCT CONCEPT AND
THEREFORE INDIVIDUALS FROM
HISPANIC ORIGIN CAN
IDENTIFY AS A VARIOUS
COMBINATION OF THESE THREE
RACES EITHER WHITE
EUROPEAN, NATIVE AMERICAN
OR ABORIGINAL AND BLACK.
THIS IS IMPORTANT BECAUSE
RESEARCH STUDIES HAVE
EVALUATED HIS PANIC
DISEASE READS AND REPORTS
RESULTS AS AN AGO AGREE
GATE WHICH MASK IMPORTANT
HETEROGENEITY UPON
SUBGROUPS AND IT'S GOOD TO
KEEP THIS IN MIND AS IT
COME BACKS IN A LITTLE BIT
IN MY PRESENTATION.
I WOULD LIKE BACKGROUND
REGARDING THE MAGNITUDE OF
THE PUBLIC-HEALTH ISSUES.
AMONG HISPANIC WOMEN IT'S
THE FIRST LEADING CAUSE OF
CANCER DEATH WITH 14% OF
ALL CANCER DEATHS
ATTRIBUTED TO BREAST
CANCER AS OF 2021.
COMPARED TO NON-HISPANIC
WHITE WOMEN, HISPANIC
WOMEN HAVE A HIGH GRADE
TUMOR DIAGNOSIS WITH LOWER
MAMMOGRAPHY AND HISPANIC
WOMEN ARE ALSO DETECTED
WITH BREAST CANCER AT
LATER STAGES.
THEY'RE DETECTED WITH
LARGER TUMORS AND HIGHER
RATES OF TRIPLE NEGATIVE
BREAST CANCER WHICH IS A
HIGHLY AGGRESSIVE CANCER
SUBTYPE AND THEY
CONTRIBUTE TO THE WORSE
BREAST CANCER PROGNOSIS
THAT IS SERVED AMONG
HISPANIC WOMEN.
SO DISCUSSING BEFORE IN
HEALTH RESEARCH, HISPANICS
ARE TREATED AS A HOMEY
GENIUS GROUP EVEN THOUGH
THEIR EXPERIENCES VARY.
HERE IS AN EXAMPLE.
AMONG PUERTO RICAN WOMEN,
BREAST CANCER ACCOUNTED
FOR 19% OF THE CANCER THAT
IS DURING THE 2014 TO 2018
PERIOD AND COMPARED TO
NON-HISPANIC WHITE WOMEN,
PUERTO RICAN ARE 90% MORE
LIKELY TO BE DIAGNOSED
WITH ESTROGEN RECEPTORS
AND NEGATIVE BREAST CANCER
AND COMPARED TO OTHER
WOMEN ON OTHER HISPANIC
SUBGROUPS WHICH IS
MEXICAN, SOUTH AND CENTRAL
AMERICAN AND CUBAN WOMEN
AND LASTLY WHILE THE
INCIDENTS OF RACE OF WOMEN
IN PUERTO RICO ARE SIMILAR
TO THOSE OF HISPANIC WOMEN
IN THE UNITED STATES THE
MORTALITY RATES ARE MUCH
HIGHER.
ARE 28% HIGHER.
IN PUERTO RICO.
AND 9% OF NON-HISPANIC
WHITE AND IN 2018 THERE'S
BEEN A BIG MIGRATION OF
HEATH CARE PERSONNEL ALSO
NEARLY ONE HALF OF THE
POPULATION IS MEDICAID
INSURED COMPARED TO 20% OF
HISPANIC IN THE
CONTINENTAL U.S. AND IT'S
IMPORTANT TO KNOW IN THE
SCIENTIFIC LITERATURE
THERE'S EVIDENCE THAT THE
SOCIAL ENVIRONMENT IMPACT
BREAST CANCER.
PHYSICAL ACTIVITY IS ONE
OF THEM.
ONLY LESS THAN 90% OF
PUERTO RICANS DO NOT
IMMEDIATE THE GUIDELINES
AND ALSO CO-MORBIDITY
DISEASE AND OWE HE BEES
TEE IS ONE OF A BIG RISK
FACTORS AND THE PREVALENCE
OF OBESITY IN PUERTO RICO
WAS 30% IN 2019.
SOME BACKGROUND, WOMEN
RISK OF BREAST CANCER IS
THE INTERACTION BETWEEN
GENETIC ENVIRONMENTAL AND
SOCIAL AND LIFESTYLE
FACTORS.
MODEL ARE USED FOR RISK
STRATIFICATION AND
ALLOWING FOR EACH WOMEN'S
BREAST CANCER RISK.
IN ORDER TO VALIDATE RISK
PREDICTION MODEL IT'S
IMPORTANT IS THEIR
PERFORMANCE, CALIBRATION
AND DIS CHRIS NAME ARE TWO
IMPORTANT WAYS OF DOING
THIS AND CALIBRATION SENDS
THE ABILITY OF THE MODEL
TO GENERATE IT CAN BE ONLY
BE COMPARED TO EXPECTING
NUMBER OF COMPARED TOED
MODEL TO THOSE OBSERVED
AND HOW WELL THE MODEL
SEPARATES THE RISK BETWEEN
THE CASE AND NON CASES
USUALLY MEASURED WITH THE
CO CORRESPONDENCE WITH
THE AUC CURVE.
ORIGINALLY THE NCI BREAST
CANCER AND THE GALE MODEL
AS WELL-KNOWN WHICH IS AT
RISK IN CLINICAL PRACTICE
ESTIMATED RISK FOR
HISPANIC WOMEN BY
COMBINING HISPANIC AGE
SPECIFIC INCIDENTS RATE
WITH RELATIVE AND
ATTRIBUTABLE RISK FROM
NON-HISPANIC WHITE WOMEN
WITH THAT METHODOLOGY
SERVED THAT THE MODEL
UNDERESTIMATED BREAST
CANCER RISK BY 18% AMONG
HISPANIC WOMEN OVER ALL
AND SINCE HISPANIC WOMEN
AND NON-HISPANIC WHITE
WOMEN DELIVERING THE
DISTRIBUTION OF RISK
CANNER AND AND HISPANIC
WOMEN IN INITIATIVE AND IT
SHOWS THAT THE HISPANIC
RISK MODEL WAS CALIBRATED
FOR U.S. BORN HISPANIC
WOMEN BUT IT APPEARED TO
OVER ESTIMATE THE RISK FOR
FOREIGN BORN WOMEN.
AND THIS IS IMPORTANT TO
NOTE BECAUSE WOMEN MAKE
DECISIONS OF WHAT
TREATMENT THEY'RE GOING TO
TAKE BASED ON THIS RISK
MODEL SO IT IS GOOD FOR US
IT WILL BE BENEFICIAL FOR
WOMEN TO GET AN ACCURATE
ASSESSMENT.
THE CORE MODELS AVAILABLE
FOR RISK PREDICTION IN
HISPANIC WOMEN THERE ARE
POTENTIAL AREAS FOR
IMPROVEMENT, IT WAS
DEVELOPED AS I MENTION
USED A POPULATION OF WOMEN
OF MEXICAN AND CENTRAL
AMERICAN DISSENT HOWEVER
AS I SAID, HISPANIC
WOMEN -- THERE'S
SCIENTIFIC EVIDENCE
THERE'S ALSO HETEROGENEITY
OF THE BREAST CANCER RATE
AMONG WOMEN VALIDATING
THIS MODEL IN OTHER
SUBGROUPS AND ALSO
CONSIDERING COUNTRY OF
ORIGIN AS AN ESTIMATED
RACE OF BREAST CANCER IN
HISPANIC WOMEN AND
ADDITIONALLY, AS I
MENTIONED, THIS MODEL WAS
SHOWN TO OVER ESTIMATE
RACE FOR HISPANIC WOMEN
AND AS I JUST SAID, IT HAS
AN IMPACT OF THE
POPULATION LEVEL AND
BECAUSE WE NEED TO GIVE
THE TOOLS TO THESE WOMEN
TO MAKE CHARACTERIZATION
ABOUT THEIR TREATMENT.
THIS IS WHY I DECIDE TODAY
DEVELOP THIS PREDICTION
MODEL.
PARTICULARLY FOR PUERTO
RICAN WOMEN SINCE I
MENTIONED THEY HAVE A
HIGHER MORTALITY RATE IN
COMPARISON TO HISPANIC
WOMEN IN THE UNITED STATES
BASED ON THE SCIENTIFIC
EVIDENCE WOMEN THAT SHOWS
THAT SOCIAL ECONOMIC
INEQUALITIES COULD BE ONE
OF THE MAIN FACTORS
CONTRIBUTING TO THE EXCESS
BREAST CANCER MORTALITY IN
THIS POPULATION.
DRIVING OUR ANALYSIS THAT
POOR PERFORMANCE OF BREAST
CANCER RISK PREDICTION
MODELS IN FOREIGN BORN
HISPANIC WOMEN MAY BE PART
DUE TO THE LACK OF THE
SOCIAL ENVIRONMENT IN
PREVIOUSLY MODEL AND IT
TAKES INTO ACCOUNT COUNTER
PER SPECIFIC I HAVE RISK
FACTORS AND SOCIOECONOMIC
FACTORS AND INCIDENTS AND
MORTALITY DATA SPECIFIC TO
PUERTO RICAN WOMEN MAY
IMPROVE RISK PREDICTION IN
THIS POPULATION.
WE ARE TESTING THIS
HYPOTHESIS USING A
ESTABLISHED POPULATION
BASED STUDY AND OF BREAST
CANCER IN 663 PUERTO RICAN
WOMEN AND DATA FROM THE
SISTER STUDY WHICH IS A
BIG PERSPECTIVE COHORT
STUDY OF 50,000 WOMEN FROM
THE U.S. AND PUERTO RICO.
WE HAVE MULTI VARIABLE
RELATIVE RISK MODEL
INCLUDING RISK FACTORS ON
SOCIOECONOMIC FACTORS AND
MAKE ABSOLUTELY RISK
PROJECTIONS FOR WOMEN WITH
SPECIFIC RISK FACTORS BY
MULTIPLYING THEIR PULL BEE
RELATIVE RISK TIMES BASED
ON AGE SPECIFIC BREAST
CANCER INCIDENTS RATE AND
TAKING INTO ACCOUNT THE
AGE SPECIFIC MORTALITY
RATES.
THIS MODEL WILL BE BUILT
USING THE EYE CARE PACKAGE
WE WILL EXAM MOST CLOSELY
ALIGN WITH THE RISK FACTOR
AND PUT ITEL IN THE MAUD
AND WE HAVE FACTORS SUCH
AS THE NEIGHBORHOOD
DEPRIVATION INCHILDHOOD
INCOME LEVEL AND HEALTH
INSURANCE.
THE ACCURACY WILL BE
TESTED USE DATA FROM THE
PUERTO RICAN WOMEN IN THE
SISTER STUDY AND
EVALUATING THE
DISCRIMINATION AND
ACCURACY OF THE RISK AND
MODEL USING A AUC CURVES.
AND THE POTENTIAL
PUBLIC-HEALTH INPUT OF OUR
WORK IS WE COULD DEVELOP A
PERSONALIZED MODEL THAT
PREDICTS ABSOLUTE RISK FOR
FOREIGN BORN HISPANIC
WOMEN THAT MANY PROVE
ACCURACY OF RISK CANCER IN
THIS POPULATION OF WOMEN
AND TO SUMMARIZE MY
PRESENTATION, HISPANICS
ARE VERY GROUPS OF
INDIVIDUALS AND IT'S
IMPORTANT TO CONSIDER THIS
HETEROGENEITY INVOLVING
THESE STUDIES AND THEY
HAVE OVER ALL
UNDERESTIMATED BREAST
CANCER RISK AND OVER
ESTIMATED BRISK CANCER
RISK FOR BORN HISPANIC
WOMEN AND PUERTO RICAN
WOMEN THEY HAVE A HIGHER
MORTALITY RATE IN
COMPARISON TO HISPANIC
WOMEN IN THE WOMEN AND IT
COULD BE A MAIN FACTOR
CONTRIBUTE TO GO THIS
EXCESS BREAST CANCER
MORTALITY.
THE PERFORMANCE OF COULD
BE I AM PROVED IF WE TAKE
INTO ACCOUNT THIS FACTORS.
I WOULD LIKE TO THANK MY
TWO FABULOUS POSTBACS AND
I ALREADY CONCLUDED HER
YEAR WITH SHE AND SHE
MOVED ON TO A PH.D IN
STATS -- IN GENETICS SORRY
AND MOLLY ROGERS AND ALSO
MY MENTORING TEAM AT
NIEHS.
ANY QUESTIONS?
[APPLAUSE]
>>NOTHING YET ON-LINE.
>>VERY NICE
PRESENTATION.
>>THANK YOU.
>>SO ONE OF THE THINGS
THAT YOU ARE FOCUSED ON IS
SOME OF THE SOCIAL AND
ENVIRONMENTAL
DETERMINANTS.
THAT ARE SPECIFIC TO
PROTECTION OR MAYBE THE
LACK OF PERFORMANCE OF A
GIVEN MODEL.
DO YOU THINK THAT ALSO
UNDERSTANDING SORT OF THE
UNDERLYING FACTORS MAY
ALSO BE USED IN SORT OF
THE OTHER DIRECTION TO
SORT OF MOVE THIS TYPE OF
RESEARCH NO A DIRECTION
WHERE NOW YOU CAN SORT OF
SAY, OKAY, I CROSSED ALL
OF THESE DIFFERENT GROUPS
OF INDIVIDUALS AND HERE IS
YOUR BETA THAT MAY PREDICT
SUCCESS OR FAILURE IN A
GIVEN HEALTH CIRCUMSTANCE.
YOU CAN START TO TEASE OUT
THE INDIVIDUAL TRAITS
WHETHER THEY ARE GENETIC,
ENVIRONMENTAL OR SOCIAL
DETERMINANTS OF HEALTH TO
TAILOR PUBLIC-HEALTH
INTERVENTION.
>>THE ANSWER IS YES.
IT'S BEEN DONE FOR A LOT
OF FACTORS.
I THINK WHAT I WILL BE
ADDING TO THE TABLE WILL
BE ALSO TESTING OR
ASSESSING WHETHER SOCIAL
ECONOMIC FACTORS COULD
ALSO IMPROVE AND TAKE THIS
MODEL A LITTLE FURTHER.
>>THAT'S IT.
THANK YOU.
[APPLAUSE]
>> Parinaz Fathi: THANK
YOU TO OUR SPEAKERS AND
EVERYBODY WHO JOINED US
IN-PERSON OR ON-LINE.
THIS CONCLUDES OUR
SESSION.
PLEASE HEAD OVER TO THE
POSTER SESSION TO SEE THE
WORK OF SOME OF THESE
INVESTIGATORS AND OTHER
INDEPENDENT RESEARCH
SCHOLARS AND PLEASE JOIN
US AGAIN TOMORROW TO HEAR
FROM A FEW OTHER
INDEPENDENT SCHOLARS.