>>WELCOME TO THE SUBCOMMITTEE
MEETING OF THE DIVISION OF
ALLERGY IMMUNOLOGY AND
TRANSPLANTATION ADVISORY
COUNCIL.
WE HAVE A TERRIFIC GROUP OF
SPEAKERS THIS AFTERNOON WHO WILL
BE BRINGING US UP-TO-DATE IN THE
ASTHMA AND ALLERGY PORTFOLIO.
BEFORE WE BEGIN, I HAVE A COUPLE
ANNOUNCEMENTS TO MAKE WHICH ARE
LOGISTICAL FOR THIS AFTERNOON
AND THE FIRST IS ANY INTERESTED
MEMBERS OF THE PUBLIC CAN FILE
WRITTEN COMMENTS WITH THE
EXECUTIVE SECRETARY OF THE
COMMITTEE WITHIN 15 DAYS OF
TODAY'S MEETING.
THOSE COMMENTS WILL BE INCLUDED
IN THE MINUTES TO THE EXTENT
THAT IS PRACTICABLE.
THE MAILING INFORMATION TO DO
THAT WAS PUBLISHED IN THE
FEDERAL REGISTER NOTICE
ANNOUNCING TODAY'S MEETING SO IF
YOU ARE INTERESTED IN SUBMITTING
COMMENTS, PLEASE DO SO.
AND THEN A REMINDER TO OUR STAFF
AND TO COUNCIL MEMBERS, PLEASE,
ANYBODY WHO IS SHOULD BE ON
CAMERA AND AND ANYBODY WHO WOULD
LIKE TO USE THE CHAT ROOM,
PLEASE DO NOT THAT WON'T BE
INCLUDED IN THE OFFICIAL MEETING
NOTES.
SO IF YOU HAVE QUESTIONS OR
COMMENTS, WAVE YOUR HAND OR
RAISE YOUR HAND USE THAT
FUNCTION AND WE'LL BE SURE TO
FIND YOU.
PATRICE BECKER WILL GIFT HISTORY
ON ONE OF THE INSTITUTES' VERY
LONGSTANDING IN CHILDHOOD
PATRICE, THE FLOOR IS YOURS.
>>THANK YOU FOR THE
OPPORTUNITY TO INTRODUCE THIS
TOPIC.
THOSE OF YOU I HAVEN'T MET I'M
THE SECTION CHIEF FOR ASTHMA AND
AIRWAY BIOLOGY IN THE DIVISION
OF ASTHMA AND IT'S MY GREAT
PLEASURE TO ZOO OUR SPEAKERS
TODAY WHO WILL TELL YOU A LITTLE
BIT ABOUT SOME OF THE OVERVIEW
AND EXCITING DATA FROM THE URBAN
CHILDHOOD ASTHMA STUDY ALSO
KNOWN EUREKA.
URECA GREW OUT OF PROGRAMS
WITHIN NIAID AND AND CHILDREN
FROM DISADVANTAGED POPULATIONS
OF COLOR IN LOW INCOME URBAN
ENVIRONMENTS WHO YOU ARE BURDEN
BIAS MA TO BETTER UNDERSTAND THE
FACTORS THAT WERE INVOLVED IN
BOTH ASTHMA PATHOGEN A SIS AS
WELL AS ASTHMA MANAGEMENT IN
THIS POPULATION AND WITH RISK
FACTORS IN THESE URBAN CHILDREN
AND CONTINUING ON WITH A
ENVIRONMENTAL SELECTION STUDY
WITH A MAJOR FACTOR IN THIS
POPULATION AS AN ASTHMA RISK AND
THE ICAS STUDY AND LED INTO
FUNDING CYCLES OF WHAT WAS
CALLED THE INNER-CITY ASTHMA
CONSORTIUM STARTING IN 2002 AND
IT WAS IN 2005 THAT THIS WAS
INITIATED.
WE'VE HAD SEVERAL MORE
ITERATIONS OF FUNDING THAT HAVE
INVOLVED INTERVENTIONAL TRIALS
WITH DIAGNOSTICS IN THIS
POPULATION AND THERAPEUTICS AND
LOOKING AT PHENOTYPING AND
PILOTING BOTH BUY LOGICS AND
IMMUNO THERAPEUTICS AND BUY
LOGICS FOR ASTHMA AND MANAGEMENT
AND THERAPY AND OUR ITERATION
WHICH WAS FUNDED LAST YEAR THAT
WAS RENAMED TO THE CHILDHOOD
ASTHMA AND URBANS SETTINGS
NETWORK.
LOOKING AT THOSE OBSERVATIONALAY
2000s THERE'S BEEN THIS URECA
BIRTH COHORT THAT'S BEEN
INVOLVED.
I TELL YOU ABOUT URECA IT WAS TO
ESTABLISH IMMUNE LOGIC CAUSES
FOR THE DEVELOPMENT OF ATM
REOCCURRING ASTHMA IN THESE
CHILDREN OF COLOR FROM URBAN LOW
INCOME POPULATIONS AND AS I
MENTIONED, IT WAS INITIATED IN
2005 AT FOUR OF THE SITES THAT
PARTICIPATING IN THE FIRST
ITERATION OF THE INNER-CITY
ASTHMA CONSORTIUM.
IT'S A LONGITUDINAL PROSPECTIVE
EVALUATION WHERE CHILDREN WERE
RECRUITED AT BIRTH AND THIS YEAR
BEGINNING THEIR AGE 17 FINAL
STUDY VISITS.
THIS STUDY INITIALLY RECRUITED
560 PREGNANT MOTHERS WITH BABIES
WHO WERE AT HIGH-RISK FORAY
LEDGE FORALLERGIC DISEASE AND 4N
RECRUITED WITHOUT PARENTAL
HISTORY DISSERVICE AND CONTROLS.
IT'S BEEN A PRODUCTIVE STUDY.
IF WE COUNT WHAT WE CONSIDERED
TO BE THE PRIMARY MANUSCRIPTS,
PRE DEFINED BY ITERATIONS OF THE
PROTOCOLS THERE ARE CLOSE TO 40
AND AS YOU WILL HEAR FROM OUR
SPEAKERS, THERE ARE MANY, MANY
MORE ADDITIONAL MANUSCRIPTS THAT
HAVE BEEN GENERATED AND ARE
CONTINUING TO BE GENERATED FROM
THIS COHORT AND THE DATA AS YOU
WILL HEAR FROM AGAIN OUR
SPEAKERS, IS NOW BEING LOOKED AT
IN THE CONTEXT OF OTHER STUDIES
AND COHORTS OF CHILDHOOD ASTHMA
IN DIFFERENT DEMOGRAPHICS
POPULATION S WITH SOME
INTERESTING FINDINGS.
SO OUR THREE SPEAKERS TODAY, YOU
HEARD BRIEFLY INTRODUCED BY TONY
AT THE OPEN SESSION AT 10:30 AND
JIM GERN PROFESSOR IN THE
DIVISION CHIEF OF ALLERGY AND
RHEUMATOLOGY AND RESEARCH IN
SPEED ADD TRICKS AND JIM HAS
BEEN THE PRINCIPAL INVESTIGATOR
OF THE STUDY SINCE 2005 AND
ACTIVE PARTICIPANT IN ALL OF THE
STUDIES AND CAROLE OBER WHO IS
INVOLVED IN THIS NETWORK FOR
MANY YEARS.
THE BLUM-RIESE DIS TINGE FISHED
SERVICE PROFESSOR AND CHAIR OF
HUMAN GENETICS AT UNIVERSITY OF
CHICAGO AND MATT ALTMAN AND ALSO
AN ASSOCIATE SCIENTIST AT THE
BENAROYA RESEARCH INSTITUTE.
I'M GOING TO TURN THINGS OVER TO
JIM SO HE CAN KICK US OFF.
>> THANK YOU, VERY MUCH FOR THE
KIND INTRODUCTION AND FOR IN
INVITE US US TO SPEAK WITH US
HERE TODAY AND I'LL TALK ABOUT
PHENOTYPES OF ASTHMA AND
RHINITIS IN CHILDREN IN URECA
COHORT.
EUREKA THERE WAS 560 CHILDREN AL
HIGH-RISK NOT ONLY WHERE THEY'RE
GROWING UP FAMILY MEMBERS EITHER
MOM OR DAD HAD ALLERGIES AND AS
MA AND AS WE NOTED DURING
RECRUITMENT IT APPLIES TO 85% OF
FAMILIES IN THE INNER-CITY AND
OUR FINAL COHORT HAD 72% BLACK
CHILDREN AND 20% HISPANIC AND 8%
OTHER AND WHAT ARE THE EARLY
ENVIRONMENTAL AND WE FOCUSED ON
FOUR MAIN CATEGORIES, HOUSE
DUST ALLERGEN AND SMOKING, VIRAL
RESPIRATORY ILLNESSES AMONG A
HOST OF OTHER EVALUATIONS.
SO THIS SLOWS THE MAJOR
PREDICTORS AND OUTCOMES
EVALUATED IN URECA AND THEY'RE
FOUR MAIN TIME PERIODS SO THAT
PERRY NATHAT -- PERINATAL AND PL
FACTORS VIRAL RESPIRATORY
ILLNESSES, ALLERGANS, MICROBES,
STRESS, POLLUTION AND DIET.
DURING THE PRESCHOOL PERIOD, THE
MAIN OUTCOMES WERE ALLEGEIC AND
RECURRENT LEADS AND THESE MAIN
EVALUATIONS WERE ABOUT THROW
YEARS OF AGE AND THEN DURING THE
SCHOOL AGE TIME PERIOD, WE
EVALUATED RESPIRATORY AND ASTHMA
PHENOTYPES FROM LONGITUDINAL
MEASUREMENTS OF WHEEZE, ALLERGIC
SENSATION AND LUNG FUNCTION AND
CURRENTLY WE'RE IN THE PROCESS
OF LOOKING AT THAT TRANSITION
BETWEEN SCHOOL-AGE AND
ADOLESCENTS AND LOOKING AT
HORMONAL INFLUENCES, THE
INFLUENCE OF OBESITY AND ASTHMA
INCIDENTS AND REMISSION AND
AGAIN, AS MA PHENOTYPES, LUNG
FUNCTION AND AIRWAY HYPER
RESPONSIVENESS.
AND IN ADDITION, WE OBTAINED TWO
MAIN SETS OF SAMPLES FOR
MECHANISTIC STUDIES INCLUDING
AIRWAYS CELLS FOR GENE
EXPRESSION AND DNA METHYLATION
AND ALSO BLOOD CELLS FOR GENETIC
STUDIES AND THESE INCLUDE 17
17Q1221 SNIPS AS WELL AS WHOLE
GENOME SEQUENCES AND CAROLE AND
MATT WILL DISCUSS THESE FACTORS.
SO WE'LL START FIRST WITH THE
FINDINGS DURING THE PRESCHOOL
PERIODND ONE OF THE SURPRISING
FINDINGS WERE INDOOR ALLERGEN
EXPOSURE WAS INVERSELY
ASSOCIATED WITH RECURRENT WHEEZE
AT AGE THREE THE UNIQUE PATTERN
OF ALLERGAN EXPOSURE IN THOSE
CHILDREN WOULD LEAD TO MORE
MORBIDITY BUT WHAT YOU SEE IN
THESE GRAPHS STARTING WITH
COCKROACH, WE HAVE EXPOSURE AND
THIS IS IN NEAR ONE AND IT WAS
THE SIMILAR FOR YEARS ONE TWO
AND THREE AND THE MORE COCKROACH
ALLERGAN IN THE HOUSE DUST OF
THE HOMES, THE LOWER OF RISK OF
RECURRENT WHOSE IT WAS A
SUBSTANTIAL EFFECT ACROSS THOSE
THREE EXPOSURE TUR TILES AND CAT
AND MOUSE.
DUST MIGHT DIDN'T FOLLOW THE
SAME PATTERN BUT AGAIN, THESE
THREE MAJOR INDOORALLER AGAINST
WERE INVERSELY ASSOCIATED WITH
RECURRENT WHEEZE.
WE LOCKED AT THE COMBINED EARLY
LIFE ALLERGAN AND MICRO BIOTA
AND COMPARED THIS TO CHILDREN
WHO WERE CATEGORIZED PAID ON
RECURRENT WHEEZE AT THREE YEARS
OF AGE.
SO FIRST OF ALL, THE KIDS AND
THE FOUR COLUMNS HERE, KIDS WHO
HAD NEITHER RECURRENT WHEEZE AND
KITS WHO HAD ONLY WHEEZING AND
NO SENSATION KIDS ONLY SENSE A
TIESED WITHOUT WHEEZE AND KIDS
WHO HAVE BOTH AND AND WE CUT
RICHNESS AND EARLY AGAIN
EXPOSURE IN THE FIRST THREE
YEARS INTO DIFFERENT CATEGORIES
BASED ON ABOVE OR BELOW THE
MEDIAN.
THE RED IS HIGH, HIGH ROBES ARE
IN AND LOW ALLERGANS AND GROWN
AND LOW MICROBES AND YOU CAN SEE
MARKET DIFFERENCES IN THE
ENVIRONMENT IF THE FIRST THREE
YEARS FOR CHILDREN IN THE
DIFFERENT OUTCOME CATEGORIES SO
KIDS WHO HAD NEITHER WHEEZE NOR
OTHER SENSATIONS WERE MOST
LIKELY TO GROW UP IN
ENVIRONMENTS THAT HAD HIGH
EXPOSURE TO BOTH MICROBES
ANDALL ALLERGAN AND LEAST LIKELO
GROW UP IN ENVIRONMENTS IN HOMES
WITH LOW MICROBIAL EXPOSURE AND
LOW ALLERGAN EXPOSURE.
IF YOU MOVE TO THE RIGHT, THE
KIDS WITH BOTH WHEEZING AND
ATOPY WERE LESS LIKELY TO GROW
UP IN HIGH EXPOSURE HOMES AND
MOST LIKELY TO GROW UP IN LOW
EXPOSURE HOMES.
SO AS WE MOVE FORWARD TO SCHOOL
AGE WE FIRST STARTED TO TAKE A
LOOK AT EARLY LIFE ENVIRONMENTAL
EXPOSURES AND ASTHMA AT AND WE
FOUND POSITIVE RELATIONSHIPS
WITH MATERNAL DEPRESSION SCORES
AND AS MA AND MATERNAL PERCEIVED
STRESS AND HAS MA AND THIS IS
PRE-NATAL OVER THE FIRST THREE
YEARS AND THE MORE ILLNESSES
REPORTED BY THE CHILD, THE
GREATER ASTHMA.
THE AND THE AIR AND HOME
EXPOSURE SIMILAR TO WHAT WE
REPORTED AT THREE YEARS OF AGE
AND THIS INVERSE RELATIONSHIP
WAS TRUE FOR KIDS WHO WERE SENSE
A TIESED AND KIDS WHO WERE NOT
SENSE A TIESED AND YOU CAN SEE
OVER ALL IN THE SENSE TIESED
KIDS HAVE A HIGHER RISK OF
ASTHMA AND
LUNG FUNCTION IN THE FIRST 10
YEARS THAT WE USED TO PUT
TOGETHER LONGITUDINAL
TRAJECTORIES AND FOR EACH OF
THESE AND A MATRIX WAS AND THESE
PHENOTYPES WERE RELATED TO EARLY
LIFE ENVIRONMENTAL EXPOSURES AND
I'LL SHOW YOU THOSE DATA IN THE
NEXT COUPLE OF SLIDES AND MATT
IS GOING TO SHOW YOU
RELATIONSHIPS TIGER WOODS
RELATIONSHIP -- GREEN EXPRESSION
AND NASAL BRUSHINGS AT 11 YEARS
OF AGE.
SO HERE WERE THE SIX PHENOTYPES
JUST NAMED FOR THEIR DIFFERENT
PATTERN OF WHEEZE, ATOPY AND
LUNG FUNCTION.
THESE WERE THE HEALTHIEST SO LOW
WHEEZE, LOW A TOP' AND WE HAVE
THIS AND THEN A GROUP OF KIDS
WITH MODERN AMOUNTS OF WHEEZING
IN LOW ATOPY AND THIS GROUP OF
CHILDREN WHO DIDN'T WHEEZE BUT
HAD HIGH ATOPY THIS GROUP WITH
MODERATE WHEEZING AND HIGH ATOPY
AND A GROUP THAT HAD THE HIGHEST
RATE OF WHEEZING, HIGH ATOPY AND
UNIQUELY EVIDENCE OF AIRWAY
OBSTRUCTION.
AND ALL OF THESE GROUPS HAD
DECENT SAMPLE SIZES SO WE CAN
REALLY START TO LOOK AT EARLY
LIFE ENVIRONMENTAL FACTORS.
AND FIRST OF ALL, WE'LL JUST
TAKE A LOOK AT PATTERNS OF
WHEEZE, ALLERGIC SNESITIZATION
AND LUNG FUNCTION AMONG THESE
SIX WE HAD TWO MODERATE WHEEZE
GROUP AND KIDS WHO HAD LITTLE OR
NO WHEEZING WITH OR WITHOUT
ALLERGICALLEGE SENSITIZATION.
THERE WERE TWO GENERAL PATTERNS
SO WE HAD THREE GROUPS HERE THAT
HAD INCREASING AMOUNTS OF ARROW
ALLERGAN SENSITIVITY SO NOT
SURPRISINGLY, THIS HIGH WHEEZE,
HIGH ATOPY AND LOW LUNG FUNCTION
AND ALSO THE MODERATE WHEEZE
GROUP AND A GROUP THAT DIDN'T
HAVE WHEEZING AND YET HAD
SIMILAR PATTERNS OF ALLERGIC
SENSITIZATION OVER TIME AND
THREE GROUPS WITH LITTLE OR NO
ALLERGIC SENSITIZATION.
WITH LUNG FUNCTION WE HAD TWO
DIFFERENT MEASUREMENTS SO FEV1
AND FEC, VERY TRADITIONAL
MEASURE OF AIRWAY OBSTRUCTION
AND REACT WHICH MEASURES THE
HETEROGENEITY OF SMALL AIRWAVES
CALENDER AND FUNCTION AND FOR
THE RATIO YOU CAN SEE THAT THE
KIDS EXCEPT FOR THIS GROUP WHICH
IS PART FOR THE NA THAT YOUNG
KIDS HAVE TROUBLE WITH SUSTAINED
EX PA TORI MANEUVER SO THEY
MIGHT BE UNDERESTIMATING AND
CLEARLY ONE GROUP STANDING APART
AND THIS HIGH WHEEZE HIGH ATOPY
LOW FUNCTION GROUP.
IF YOU LOOK AT THE REACT ANTS
AREA THEY'RE MUCH MORE PARALLEL
AND AND NEXT WE'LL LOOK AT
CLINICAL ASSOCIATIONS WITH THE
PHENOTYPES SO THEY'RE ALL IN THE
COLUMNS HERE AND THEN THE
MEASUREMENTS ARE GROUPED IN
TERMS OF CO-MORBIDITY SO ASTHMA,
ECZEMA, CHRONIC NASAL SYMPTOMS
AND LUNG FUNCTION MEASUREMENTS
SUCH AS PC20 AND THIS WAS AT AGE
10 AND FEV1 AT AGE 10 AND
MEDICATION USE IN THE 10 YEAR OF
LIFE AND WHAT CAN YOU SEE BY
LOOKING AT THE DIFFERENT COLUMNS
IS IT'S REALLY THIS HIGH WHEEZE,
HIGH ATOPY LOW LUNG FUNCTION
THAT HAS THE CLOSEST ASSOCIATION
WITH CO-MORBIDITY AND A LITTLE
MORE ECZEMA WITH THIS MODERATE
WHEEZE HIGH ATOPY GROUP AND THE
FUNCTION FUNCTIONS WERE MOST
ABNORMAL IN THIS GROUP AND MOST
LIKELY TO BE USING EITHER INHALE
STEROIDS OR OR ALTER VOIDS SO
WE'LL LOOK AT ENVIRONMENTAL
EXPOSURES AND THE PHONE OWE
TYPES AND WE'RE LOOKING AT
MATERNAL DEPRESSION SCORES AND
MA THESE ARE CUMULATIVE FOR THE
FIRST THREE YEARS AND THE
ALLERGAN EXPOSURE INDEX SO THIS
IS IF YOU ADD UP EXPOSURE TO IN
YOU HOUSE DUST TO CAT, DOG,
MOUSE AND COCKROACH, THAT'S WHAT
THIS INDEX IS AND HOUSE DUST IS
A MEASUREMENT OF FUNGEL EXPOS
EXPOSURE.
SO, MATERNAL STRESS AND
DEPRESSION WAS ASSOCIATED WITH
OTHER WHEEZING PHENOTYPES BUT
MOST CLOSELY ASSOCIATED WITH
THIS MODERATE WHEEZE AND IN
CONTRAST THE HIGH WHEEZE, LOW
LUNG FUNCTION PHENOTYPE HAD THE
LOWEST ALLERGAN EXPOSURE IN
EARLY LIFE, CONTINUING THAT
THEME WE SAW AT AGE THREE AND
AGE SEVEN.
ALSO, HAD INCREASED EXPOSURE IN
EARLY LIFE TO ERGOSTEROL AND
THIS IS A MEASUREMENT OF FUNG
ALEX POSE YOU'RE.
THIS ANALYSIS GOES THROUGH UNTIL
AGE 12 AND WE'RE DEVELOPING THIS
DATA THERE WERE FOUR WITH
PATTERNS WE USED A SIMILAR
VALUED APPROACH HERE AND KIDS
HAVE LOW TO MINIMUM RHINITIS
EVERYONRYAN OVERTIME AND THOSE E
PERSISTENT RHINITIS IN THE GREEN
AND THOSE WHO HAVE PERSISTENT
RHINITIS THAT DECREASES A LITTLE
BIT IN EARLY LIFE AND THIS
PERSISTENT RHINITIS PHENOTYPES
SEEMS TO BE THE ONE THAT IS MOST
PROBLEMATIC WITH A FAMILY
HISTORY OF ALLERGIC DISEASE AND
PRO NAL AT POST EXPOSURE AND
ANTIBIOTIC USE AND RAPID WEIGHT
GAIN IN EARLY LIFE AND CLOSELY
WITH BIOMARKERS AND ASTHMA RISK
AND I'LL JUST MENTION AS WELL
THAT THESE PATTERNS ARE RHINITIS
REALLY PARALLEL TO THE LARGE
EXTENT OF WHAT WE FOUND IN TERMS
OF PATTERNS OF WHEEZE SO, THIS
IS A SUMMARY OF SOME OF THE PURE
EQUAL A DATA AS A INDIVIDUAL
COHORT AND AND MODERATE TO
SEVERE AS MA AND MOST OF THE
ASTHMA IN URECA IS MILD AND ALSO
THE DATA ARE POPULATION SPECIFIC
AND IT'S DIFFICULT TO COMPARE
ACROSS DIFFERENT POPULATIONS AND
ACROSS DIFFERENT ENVIRONMENTS
AND THEY HAVE DIFFERENT
POPULATIONS OF CHILDREN AND THIS
IS WHERE COLLABORATIONS WITHIN
THE ECHO, THE ENVIRONMENTAL
INFLUENCES ON CHILD HEALTH
OUTCOMES AND CROW CHILDREN'S
RESPIRATORY AND ENVIRONMENTAL
WORKGROUP PROGRAMS HAS REALLY
BEEN WONDERFUL AND THESE ARE TWO
PROGRAMS SUPPORTED BY THE
NATIONAL INSTITUTE OF HEALTH AND
SIX OWE IS COHORTS AND THESE
WERE ECHO WAS FUNDED IN CREW IS
ONE OF THE 31 ECHO AWARDS AND
CONSISTS OF 13 BIRTH GOERS THAT
INCLUDE URECA AND 9,000 NEWBORNS
AND THE OUTCOMES ARE RELATED TO
CHILDHOOD ALLERGY AND ASTHMA AND
TOGETHER, EITHER ECHO OR CREW
REALLY PROVIDE POPULATION
DIVERSITY WITHIN EACH OF THESE
STUDIES AND THIS IS IN TERMS OF
GEOGRAPHIC DIVERSITY ALSO THE
YEAR OF BIRTH.
13469 COHORTS ARE STILLEN
ROLLING AND INCLUDING URBAN,
SUBURBAN AND RURAL CHILDREN AND
A VERY REPRESENTATIVE VARIETY OF
THESE ARE THE FOUR URECA COHORTS
IN BLUE AND MAD SIN IS THE
LEADERSHIP CENTER AND ROW HAS
BEEN THE COORDINATING CENTER FOR
CAUSE AND YOU CAN SEE IF WE ADD
IN THE CREW COHORT WE HAVE 13
NOW WITH BETTER REPRESENTATION
RA CROSS THE COUNTRY WE HAVE A
COUPLE OUST WEST AND A COUPLE IN
THE SOUTH AND SO FOURTH AND YOU
REALLY SEE TREMENDOUS DIVERSITY
IF YOU ADD IN THE 69 COHORTS
THAT ARE PARTICIPATING IN ECHO
AND WE HAVE U.S. CHILDHOOD
ASTHMA AND PATTERNS FROM THE
ECHO CONSORTIUM TO HIGH FIE
HIGH-RISK GROUPS INFORM PRIMARY
PREVENTION.
THESE ARE THE PAR PARTICIPATING
SITES AND AND THE STUDY DESIGN
WAS A DISTRIBUTE META ANALYSIS
INCLUDING URECA OVER 12,000
CHILDREN AND THE OUTCOMES WAS
THE INCIDENTS OF Dr. DIAGNOSED
ASTHMA WHICH ACROSS THE UNITED
STATES.
OF THIS STUDY WAS LED BY
CHRISTINE JOHNSON.
IT'S EXPECTED THIS YOU LOOK AT
ASTHMA INCIDENTS RATES ONE OF
THE IMPORTANT FACTOR IS FAMILY
HISTORY IF YOU LOOK AT THE TWO
COLUMNS HERE WE HAVE DATA FOR
CHILDREN WITH NO FAMILY HISTORY
OF ASTHMA AND IF
YOU LOOK ACROSS KIDS WITH FAMILY
HISTORY HAVE GREATER INCIDENTS
RATES OVER ALL AND THE
INFLUENCES OF SEXES AS EXPECTED
WE'VE KNOWN THIS FOR PREVALENCE
DATA FOR YEARS AND GREATER
INCIDENTS IN BOYS UP UNTIL ABOUT
TUBER PEE AND THOSE LINES CROSS
AND THEY STILL LOOK THERE IN THE
KIDS WITH THE POSITIVE FAMILY
HISTORY BUT WHAT IS REALLY
REMARKABLE IF YOU LOOK AT THE
INFLUENCE OF RACE ON ASTHMA
INCIDENTS, INCIDENTS HIGHER IN
BLACKS OR IF YOU LOOK IN THE
FIRST FEW YEARS LIFE YOU HAVE
THREE TIMES THE ASTHMA INCIDENTS
RATES IN NON HISPANIC BLACK
CHILDREN COMPARED TO NON
HISPANIC WHITE CHILDREN.
IF YOU GO OUT INTO THE
ADOLESCENTS AND TEEN YEARS, THE
INCIDENTS THERE IS HIGHER IN
WHITE CHILDREN AND IF YOU ARE
PREDISPOSED TO ASTHMA IN YOUR A
BLACK CHILD, YOU ARE GOING TO
GET THAT DISEASE IN EARLY LIFE
WHICH IS A PROBLEM AND WE KNOW
THAT EARLY ONSET ASTHMA IS MORE
SEVERE AND HAVE MORE AND MORE
MORBIDITY AND JUST LOOK AT THE
DISPARITY IF CHILDREN HAD A
POSITIVE FAMILY HISTORY OF
ASTHMA AND JUST SKY HIGH RATES
WE HAVE A SECOND PAPER THAT IS
JUST BEEN PUBLISHED IN THE LAST
WEEK LED BY ANTON ELLA AND
DIANNE GOLD AND THIS IS AN ECHO
CREW PAPER AND SO DO
NEIGHBORHOOD LEVEL SOCIAL
ECONOMIC INDICATORS EXPLAIN
THESE BIG RACIAL AND ETHNIC
DISPARITIES IN CHILDHOOD
WHEEZING AND ASTHMA?
WE USED THE CREW POPULATION OVER
5800 CHILDREN AND 43,000 PLUS
THEY WERE A HAZARD MODEL TO
DEVELOP HAZARD RATIOS OF ASTHMA
INCIDENTS AND LOGISTIC
REGRESSION TO CAT CUE LATE THE
ODDS RATIO FOR EARLY AND
PERSISTENT WHEEZE.
THE THE MAIN EXPOSURE WAS
NEIGHBORHOOD LEVEL AND DEFINED
BY U.S. CENSUS TRACKS LINKED TO
PARTICIPANT'S BIRTH ADDRESS AND
DECADE OF BIRTH IN THE MAIN
OUTCOME IS THE PREVALENCE OF
EARLY PERSISTENT WHEEZE AND THE
DATA ARE THE ASTHMA INCIDENTS
DATA HERE ARE THE MAIN FINDINGS
AND NOT PRICINGLY RACE,
ETHNICITY, POVERTY AND LOWER
HOUSEHOLD INCOME INCREASED RISK
FOR CHILDHOOD ASTHMA AND
HOWEVER, THEY WERE A RISK FACTOR
AFTER ADJUSTING FOR NEIGHBORHOOD
INCOME SO THE INTERACTIONS
BETWEEN RACE ETHNICITY AND
SOCIAL ECONOMIC SKATERS WERE NOT
SIGNIFICANT THAN BLACK AND
SIGNIFICANT CHILDREN IN HIGHER
INCOME NEIGHBORHOODS STILL HAD
INCREASED ASTHMA INCIDENTS
RATES.
SO IN CONCLUSION REGARDING URECA
ASTHMA PHENOTYPES WE IDENTIFIED
SIX.
THE HIGH WHEEZE IS AN
INTERESTING ONE SO IT'S A T-2
LOW PHENOTYPE IN RICH FOR ASTHMA
AND ASSOCIATED WITH MA TERNE AT
STRESS AND DEPRESSION AND THERE
COULD BE A NUMBER OF SEW
VARIANTS ASSOCIATED WITH THOSE
AND THE PHENOTYPE WITH THE
GREATEST MORBIDITY WITH LOW
ALLERGAN EXPOSURE IN EARLY LIFE
AND HIGH FUNCTIONAL EXPOSURE AND
YOU WILL SEE IN THE NEXT COUPLE
PRESENTATIONS AND BASED ON THE
OUTCOMES AND BIOSPECIMENS THAT
WERE GATHERED THROUGHOUT THE
YEARS AND IMPORTANTLY, WE CAN
LEARN A LOT FROM URECA BUT THESE
CHILDREN HAVE SOME OF THE SAME
CHALLENGES IN ALL FOUR OF OUR
URECA SITES AND IT'S I WILL LUS
TRA TIVE TO COMPARE THEM TO
STUDIES AND CHILDREN ACROSS THE
COUNTRY.
THE ASTHMA RATES ARE AMONG THE
HIGHEST IN THE U.S. AND IN ECHO
THEY ARE THE HIGHEST.
THERE'S ONSET OF DISEASE AND WE
NEED TO UNDERSTAND WHAT THOSE
FACTORS ARE CLEARLY LOW
SOCIOECONOMIC STATUS IS A STRONG
CONTRIBUTING FACTOR BUT IT
DOESN'T ACCOUNT FOR ALL OF THE
INCREASED RISK IN AFRICAN
AMERICAN CHILDREN RAISING
QUESTIONS AS TO WHAT DOES AND
WHAT MIGHT THOSE OTHER FACTORS
BE AND LISTED THROW
POSSIBILITIES HERE AND WE HAVE
THIS PERSISTENT SIGNAL FOR
MATERNAL STRESS AND DEPRESSION
AND THIS IS BEFORE THE MASS HAS
APPEARED AND THERE CAN BE
ADDITIONAL STRUCTURAL EQUITIES
THAT HAVEN'T BEEN EVALUATED YET
AND THEN GENE BY ENVIRONMENT
INTERACTIONS SO WITH THAT I'D
LIKE TO ACKNOWLEDGE GREAT
COLLEAGUES AND INSTITUTIONS AND
IT WAS STARTED IN ICA AND THE
INVESTIGATORS HERE ARE LIST
INSIDE BOLD TYPE AND AT BOSTON
UNIVERSITY COLOMBIA AND JOHN
HOPKINS WITH THERE'S BEEN A TALK
SOON AND CERTAINLY WE ARE
THANKFUL FOR SUPPORT OF THE NIH
AND IT'S BUILT A TERRIFIC AND
COMPREHENSIVE PICTURE OF ASTHMA
IN URBAN CENTERS THANK YOU VERY
MUCH FOR YOUR ATTENTION.
PATRICE DO YOU WANT QUESTIONS
NOW OR HOLD THEM?
WE CAN DO IT EITHER WAY.
THEY'RE REALLY DISTINCT IN TERMS
OF THE FOCUS ON CLINICAL VERSUS
TRANCE TRIP OMICS AND IF ANYONE
HAS QUESTIONS WE WOULD BE HAPPY
TO TAKE THEM AND WE CAN ALWAYS
HAVE ADDITIONAL QUESTIONS AFTER
ALL THREE TALKS IF WE HAVE TIME.
THAT WAS A WONDERFUL
PRESENTATION AND VERY
PROVOCATIVE YOU SEE SURPRISING
IN WORSE ASSOCIATION BETWEEN
EXPOSURE AND WHEEZE AND ATOPY SO
I JUST WANTED TO HOPE THAT WE
LEARN MORE IN THE NEXT TWO WEEKS
BUT OVER ALL WHAT IS YOUR SENSE
OF WE ARE VERY INTERESTING IN
THIS ASPECT OF HOW IT MIME
IMPACT NOT ONLY OF COURSE ALL
KINDS OF BUT IMMUNE CELLS FOR
SURE AND WE HAVE VERY NEW MODEL
THAT'S WE HAVE ESTABLISHED WE'VE
SEEN IMPACTING ON CELL DEATHS SO
ANY THOUGHTS THAT YOU HAVE
THERE?
WE THOUGHT IT WAS A SNELL DUE
THE MICROBIOME THE MOUSE BRINGS
INTO THE HOME OR THE COCKROACH
AND IT TURNED OUT NOT TO BE THE
CASE.
SO, YOU KNOW, HOW COULD INCREASE
ALLERGAN EXPOSURE HAVE
BENEFICIAL EFFECTS, WELL, YOU
KNOW, I STARTED MY WORK WITH
BIRTH COHORTS IN THE COST BIRTH
COHORT AN THERE THE STRONGEST
FACTOR IN TERMS OF EXPOSURE WAS
EXPOSURE TO DOGS.
SO SOME COMMONALITY THERE AND
THEN, STUDIES ON FARMING
ENVIRONMENTS HAVE SHOWN THAT
EXPOSURE TO THE CENTRAL WES CON
SIN COHORT THE MORE ANIMALS THAT
MOTHERS EXPOS TO DURING THE
PRE-NATAL PERIOD AND EARLY POST
NATAL PERIOD THE BETTER THE KIDS
DO.
SOME OF THIS IS NO DOUBT GOING
TO BE DUE TO THE MICROBIOME BUT
THERE MAY BE EFFECTS OF JUST
BROAD ANTIGEN EXPOSURE EARLY
LIFE AND WE'VE LEARNED FROM THE
LEAP STUDY JUST HOW POWERFUL
THAT IT CAN BE ORALLY AND
PERHAPS WE'RE SEEING THE SAME
SORT OF THING IN THE RESPIRATORY
TRACT AND THAT ANTIGEN EXPOSURE
MAY BE SOMETHING THAT HELPS WITH
MATURATION OF DENDRITIC CELLS OR
TRACKING THEM INTO THE AIRWAY.
>> YES, SO, I WILL MENTION TO
YOU, WE HAVE PUBLISHED ONE PAPER
BUT WE HAVE NOT YET PUBLISHED
THE NEXT ONE WHICH IS THE MORE
EXCITING STUDY WE ARE DOING.
MAYBE BETWEEN THE MICE THIS IS
AN OPPORTUNITY BECAUSE IT'S A
STRIKING GENE ASSOCIATED WITH
CELL MIGRATION AND BOTH, AND
THIS WAS AN OLD PAPER OF A
PUBLISHED BY ALAN AND NEVER
PICKED UP OF THE IT WAS MA
MACROPHAGES AND I WAS HOPING
SOMEONE WOULD BE DOING THIS TYPE
OF AND IT WOULD BE NICE TO
DISCUSS IS THIS FURTHER AND GET
SAMPLES FROM YOU AND YOUR
COLLEAGUES TO SEE WEATHER WE
COULD DO SOMETHING TOGETHER.
>> THANK YOU SO MUCH.
>> MATT, DO YOU WANT TO ASK M.
YOU HAVE YOUR HAND UP?
THIS IS A GREAT PRESENTATION
SKID A QUESTION MAYBE A LITTLE
SERVE SELFING BUT I LOOKED AT
THE PIC PICTURES AND NO FAMILY
HISTORY VERSUS FAMILY HISTORY OF
ASTHMA AND IN THE FAMILY HISTORY
OF COURSE MUCH HIGHER BUT
DECREASING WHERE THE LACK OF
FAMILY HISTORY IT'S PARTICULAR
THE GIRLS CONTINUALLY INCREASING
AND JUST SORT OF SPECULATING
ABOUT WHAT IS GOING ON THERE AND
WHAT YOU THINK THE DIFFERENCE IS
IN TERMS OF PHENOTYPES AND
MECHANISMS AND I DON'T KNOW IF
IT WAS DISCUSSED IN THE PAPER OR
YOU'VE DONE IT THROUGH ECHO.
IT'S HARD BECAUSE WITH
PHENOTYPES THEY'RE BASED ON WHEN
THEY START AND SO FOURTH SO THAT
MAKES IT A LITTLE THEY ARE
STARTING PEARL LATE AND THERE'S
SPECIFICS POLLS OF THAT IN THE
LITERATURE AND ONE OF THE NEXT
STUDIES WE'LL DO IN ECHO AND
CREW IS TO LOOK AT INFLUENCE OF
AIR POLLUTION AND THEY'RE BORN
IN THEY HAVE SENSITIVE LUNGS
WITH AND FERNANDO MARTINEZ
DESCRIBED THE PHENOTYPE OF
ASTHMA THAT BEGINS IN TEENAGE
GIRLS IN THEY'RE OVERWEIGHT,
GOING INTO PUBERTY YOU GET ONSET
AND THERE'S A FORM OF ASTHMA
THAT IS HORMONALLY DEVIATED THAT
STARTS AT 10, 11, 12 YEARS OF
AGE.
WE'RE JUST FINDING DIFFERENT
FORMS OF ASTHMA AND
>> THANK YOU, CAN YOU SEE MY
SLIDES?
>> YES.
>> AND YOU SEE THE RIGHT VIEW?
>> OK.
LET ME JUST GIVE MY LASER
POINTER AND I'M GOING TO THANK
THE PA TREES AND OTHERS FOR IN
INVITING US TO GIVE THIS
PRESENTATION.
AND TO PREVIOUS SPEAKERS TO
GIVING AN EXCELLENT BACKGROUND
TO WHAT I'M ABOUT TO TALK TO YOU
OVER THE NEXT 20 MINUTES OR SO.
SO, MY LAB HAS BEEN REALLY
FOCUSED OVER THE PAST MANY YEARS
AND I'M TRYING TO PARSE OUT THE
EFFECTS OF GENES AND ENVIRONMENT
AND AS MA AND ALLERGY AS A
DISEASE AND ALSO AS INDIVIDUALES
AND THESE EFFECTS ARE FROM BOTH
ENDS OR REAL REAL MEDIATE BY THE
TRANSPORTATION DESCRIPTIONAL
LANDSCAPES.
I'M GOING TO TALK TO YOU ABOUT
AGAIN HE HAD TICKS AND EPI
GENETICS AND THE TRANSCRIPTIONAL
SINGLES IN THE SAME GROUPS OF
CHILDREN AND TELL TWO DIFFERENT
STORIES I
NEED TO STOP SHARING FOR A
MINUTE.
CAN YOU SEE THAT?
SO I'M GOING TO START OFF WITH A
SERIES OF STUDIES THAT WE'VE
DONE THAT STARTED WITH A GWAS WE
PERFORMED A FEW YEARS AGO IN
OVER 9,000 CASES AND 318,000
CONTROLS WHO WERE PARTICIPANTS
SO THOSE ARE WHITE, BRITISH
INDIVIDUALS AND WE CONDUCTED
SEPARATE GWAS AND CHILDHOOD
ASTHMA AND I'M SHOWING HERE THE
PLOT FOR CHILD ONSET ASTHMA
WHERE THE VALUES ON THE BUY
ACTION I GUESS AND THE LOCATION
OF EACH INDIVIDUAL VARIANT WHICH
IS A DOT IS SHOWN ON THE X AXIS
AND THERE'S LOTS OF LOW SIDE
ASSOCIATED WITH CHILDHOOD ASTHMA
AND THIS IS 17 Q1 2LOCUS
REPLICATED CHILDHOOD ONSET
ASTHMA LOCUS.
AND THIS PEAK OF SIGNAL OF
SIGNIFICANT SNIPS IS REFLECTING
THE STRUCTURE OF THIS REGION
SHOWN HERE ON TWO LOCUS PLOTS SO
NOW WE'RE LOOKING AT AT THAT
LOCUS SPECIFICALLY AND WE'VE
LOOK AT CHILDHOOD ONSET RESULTS
AND AND P VALUES ON THE Y AXIS
AND THE GENES IN THIS REGION ON
THE X AXIS AND THE FIRST REALLY
STRIKING FINDING IS IS THAT
THERE IS ABSOLUTELY NO SIGNAL AT
THIS LOCUS AND WE USED A STRICT
CRITERIA FOR ADULT ONSET ASTHMA
BECAUSE WE WERE TRYING TO AVOID
ANYTHING IN THAT PERIOD OF
PUBERTY SO WE HAD 26 AND 75
YEARS OF AGE AND YOU CAN SEE
THAT THERE'S JUST NOTHING HERE
AND IN THE CHILDHOOD ONSET LOCUS
WE SEE HIGHLY SIGNIFICANCE
ASSOCIATIONS BUT A VERY BROAD
REGION OF ASSOCIATION WHICH
SPANS 150 KILL' BASIS WHICH IS
LARGE EVEN IN EUROPEAN
POPULATION AND THE COLORS OF
THESE VARIOUS SNIPS THAT ARE
SHOWN IN CIRCLES, THE CLOSER TO
RED YOU ARE THE MORE HIGHLY
CORRELATED WITH THE SNIPS ARE
WITH EACH OTHER SO YOU CAN PRO
DICTIONARY THE NINO TYPE OF
ANOTHER SNIP AND WE REFERRED TO
THIS AS LINKAGE IN EUROPEANS
IT'S DIFFICULT TO SAY WHICH OF
THESE MANY VARIANTS IS ACTUALLYL
CAUSAL AND WHICH ARE TAGGING
ALONG BECAUSE THAT WITH THE
CAUSAL VARIANTS.
ALL OF THE SNIPS BECAUSE OF THIS
HIGH LT ARE ASSOCIATE WITHED
EXPRESSION OF TWO GENES, GSD AND
B AND ORMD F-3 AND THESE ARE THE
TWO PRIMARY CANDIDATE GENES OF
THIS LOCUS BUT IT'S VERY
DIFFICULT TO FIGURE OUT WHICH
GENE IS CAUSAL AND WHICH
VARIANTS ARE EFFECTIVE IN WHICH
GENE.
SO THIS IS SHOWING A LINKAGE
PLOT IN EUROPEAN ACCESS TREE
INDIVIDUALS IN THE STUDY THAT WE
DID WHERE WE SELECTED NINE SNIPS
ACROSS THIS BROAD REGION THAT
MORE OR LESS CAPTURED THE LD
PATTERNS AND CONSORTIUM THAT FOR
THE THIS HIGH CORRELATION
BETWEEN THE VARIANTS AND
CORRESPONDING TO THE FIVE SNIPS
THAT ARE WHAT WE CALL THE CORE
REGION OF THE LOCUS IN THIS
ORANGISH RED ON THE FLANKING
REGION BLUE AND GREN ON THE
OTHER SIDE AND NOW CONTRAST THAT
TO WHAT WE SEE WITH AFRICAN
AMERICANS AND IT'S OBVIOUS IN
AFRICAN AMERICANS, OR AFRICAN
ANCESTRY INDIVIDUALS, THERE'S
BEEN A SIGNIFICANT BREAKDOWN OF
THE THE LD DUE TO THE OLDER AGE
OF THESE POPULATIONS OF THE
COMBINATIONS BETWEEN VARIANTS SO
IN THE AFRICAN AMERICANS,
SEPARATE OUT THE EFFECTS OF
VARIANTS IN THIS BLOCK OF THEIR
SNIPS THAT ARE TOTALLY
CORRELATED IN EUROPEAN AMERICANS
AND SO WE GENOTYPE THESE
VARIANTS AND THE CREW COHORTS
AND WE META ANALYZE THOSE DATA
WITH A LARGER SAMPLE OF AND WHEN
WE DID THAT AND TOOK INTO
ACCOUNT THE TWO GROUPS
SEPARATELY, SIMILAR EFFECT SIZES
BUT IN THE AFRICAN AMERICANS
THERE WERE TWO ASSOCIATED WITH
ASTHMA AND THOSE TWO ARE IN HIGH
LD AND EVEN IN THE ASTHMA
POPULATION AND WE CAN EXCLUDE
ALL THE OTHER SNIPS ACROSS THIS
REGION AND SOME HAD OPPOSITE
ASSOCIATIONS IN THAT THE REAL
BITS ASSOCIATED WITH ASTHMA AND
EUROPEANS IS ALLELE WITH NON
RISK IN THE AFRICAN AMERICANS.
IN ADDITION, WE WANTED TO SEE IF
WE CAN PURSE OUT AND THE TWO
GENES AND SO WE USED SEEN
EXPRESSION DATA PROVIDED TO US
FROM CELLS AND BLOOD CELLS IN
EUREKA CHILDREN TO SEE IF WE CAN
START TO GET AT NOT ONLY THE
CAUSAL SAMPLE THE CAUSAL GENE.
AND AFTER WE ACCOUNTED FOR LD
WITH ANOTHER SNIP THAT IS A
STRONG ENHANCER FOR BOTH GENES
AND HOWEVER WE SAW A VERY
UNEXPECTED RESULTS WHEN WE
LOOKED AT UPPER AIRWAY
EPITHELIAL CELLS BECAUSE WE SAW
A VERY SIGNIFICANT ASSOCIATION
BETWEEN GSDMB AND THE LEAD SNIPS
AND NOT SO MUCH WITH THE SECOND
ONE AND NEITHER ASSOCIATED WITH
THE CELLS SO THIS DATA REALLY
SUPPORTED GSDMB AS THE CAUSAL
GENE WITH ONSET ASTHMA AND THIS
SNIP OR ONE THAT IS LD WITH IT
BECAUSE WE DIDN'T TYPE EVERY
SNIP OF THE REGION WAS IN ONE
STUDY SHOWED THAT ALL THE
FUNCTIONAL PROPERTY OF THE
PROTEIN AND THE GASTRO AND GREAT
CANDIDATE GENES FOR ASTHMA AND
THEY IMMEDIATE OPTOSIS SO WE
HAVE ON GOING STUDIES NOW AND
OTHERS IN CREW CONSORTIUM TO
REALLY TRY TO UNDERSTAND HOW
THESE GAS TOE AND I WILL ALSO
MENTION AFTER WE PUBLISHED THIS,
TWO OTHER STUDIES ALSO CONCLUDED
FROM THE WORK THAT IT'S NOW WE
WERE VERY INTRIGUED BY THE
UNUSUAL LD PATTERNS OR THE BIG
DIFFERENCE IN LD PATTERNS WHICH
IN THE AFRICAN AMERICANS AND THE
EUROPEAN AMERICANS AND WE
WONDERED WHETHER THERE WERE AN
ACTUAL AND CHARLES WASHINGTON
TOOK ON THIS STUDY ON THE FIVE
SNIPS THAT WERE IN THE CORE
REGION AND EXAMINE THE EFFECTS
OBJECT ASTHMA LIST IN THE
CONSORTIUM AND WHAT I'M SHOWING
YOU HERE, THESE ARE THE FIVE
SNIPS IN THE CORE REGION THAT
INDICATES THE SNIPPET THAT WE'VE
REPORTED IS THE LIKELY CAUSAL
SNIPPING THESE ARE THE FREQUENCY
IN EUROPEAN AMERICANS AND
AFRICAN AMERICANS AND THESE TWO
TYPES ACCOUNT FOR 90% OF ALL
ACROSS THIS REGION WERE IN
AFRICAN AMERICANS IT ONLY
ACCOUNTS FOR 57% AND SO THIS WAS
IMMEDIATELY QUITE INTERESTING TO
US AND WE DID A TEST OF
ASSOCIATION OF THE PAP LOW TYPE
USING THE NON RISK IN YELLOW.
HAPPEN LOW TYPE AND WE'RE
CALLING THIS THE RISK AND OUR PS
STUDY IN CREW.
FOR THE AFRICAN AMERICANS THERE
WAS REALLY NOT MUCH EVIDENCE IN
THE ASSOCIATION WITH ASTHMA WITH
THIS PARTICULAR HAPLOTYPE.
THE ODDS RATIO WAS GREATER THAN
ONE BUT NOTHING ELSE WAS
CONVINCING WITH ALL THE DATA YOU
HAVE.
WE LOOKED AT THE OTHER
HAPLOTYPES AND WHAT WE
DISCOVERED IN THE SAMPLE WAS
THERE WERE TWO FAIRLY COMMON
HAPLOTYPES IN AFRICAN AMERICANS
THAT ARE ABSENT IN EUROPEAN
AMERICANS AND BOTH CARRY THE
RISK ALLELE AT THIS CAUSAL SNIP.
AND IN FACT, ONE OF THEM HAS
VERY SIGNIFICANT AND HIGH ODDS
RATIO FOR ASTHMA AND THE SECOND
ONE IS MIDWAY BETWEEN THOSE TWO
SUGGESTING THERE'S SOMETHING
ABOUT THIS HAPLOTYPE 4 THAT IS
CARRYING ADDITIONAL RISK FOR
ASTHMA IN THE AFRICAN AMERICANS.
SO WE THEN USED WHOLE GENOME
SEQUENCES THAT WE HAVE IN BOTH
EUREKA AND APIK AND TWO PUBLIC
DATASETS ON EIGHTH AND C.A.A. PA
TO IDENTIFY VARIANTS THAT ARE
RICH IN AFRICAN AMERICANS IN
ABSENT IN EUROPEANS.
AND I'M GOING TO SUMMARIZE ON
THE NEXT SLIDE, A VERY
COMPLICATED LONG STUDY BUT WE
IDENTIFIED A 24KB CRITICAL
REGION THAT WAS SHARED BY ALL
HAPLOTYPE 4 CHROMOSOMES BUT NOT
ON THE OTHER CHROMOSOMES AND
CLEARLY NOT ANY EUROPEAN
CHROMOSOMES AND THIS 24KB REGION
INCLUDED NINE SNIPS SHOWN IN RED
AND THEY ARE AFRICAN SPECIFIC
AND ONLY RECENTLY EVEN IN THE
DATABASEs BECAUSE NOW
EVERYBODY IS DOING GENOME
SEQUENCING BUT UP AT THE POINT
WE DISCOVERED THEY WERE THEY
WERE NOT PREVIOUSLY ACKNOWLEDGED
OR INCLUDED IN ANY.
THESE SNIPS WERE CANDIDATE SNIPS
FOR THE DRIVING OF THE
ASSOCIATION OF ASTHMA IN AFRICAN
AMERICANS AND THIS SNIP IS ONE
OF THE FIVE WE INCLUDED AND THIS
REGION EXTENDS FROM THE GSDMB
AND ALL THE WAY THROUGH TO
REGION OF.
THE FIRST THING WE ASKED WAS,
ARE THESE SNIPS AND THESE SNIPS
ARE ALL VERY HIGH LD BECAUSE
THEY OCCUR IN THE SAME
HAPLOTYPES BUT ARE THESE SNIPS
ASSOCIATED WITH THE EXPRESSION
OF ANY GENE IN AIRWAY EPITHELIAL
CELLS WITHIN OMEGA BASE FLANKING
REGION OF EACH GENE OF EACH
SNIP.
WE WERE PLUS OR MINUS 500KB
AROUND EACH SNIP AND TEST FOUR
ASSOCIATIONS AND THERE'S ONE
GENE IN THIS REGION THAT THESE
FIRST EXPRESS WAS ASSOCIATED
WITH GENOTYPE SNIPS AND THAT WAS
GSDA AND IT'S 50 KILL A BASIS
DISTAL TO THIS LAST SNIP AND YOU
CAN SEE IN THIS FIGURE THAT
CARROTTING OF THE T ALLELE, THE
AFRICAN-SPECIFIC ALLELE IS
ASSOCIATED WITH HIGHER
EXPRESSION OF GSDMA AT THE
ALLELE CELLS AND THIS OCCURS
ABOUT 12% FREQUENTLY IN AFRICAN
AMERICANS.
IT'S LESS THAN .01 FREQUENCY IN
EUROPEANS AND IN THE LARGE
DATABASE AND IT WASN'T PRESENT
ALONE SO IF THESE SNIPS ARE
REGULATING THE EXPRESSION, WE
SUGGESTED THAT THIS MUST BE MORE
SNIPS MUST BE RESIDING IN AN
ENHANCER REGION THAT IS
REGULATING EXPRESSION OF GSDMA
SO WE USE PUBLICLY AVAILABLE
DATA TO LOOK AT THAT AND WHEN
I'M SHOWING HERE NOW, ACTIVE
ENHANCER MARKS AND TRACKS THOSE
AND UNDER THIS ARE TRACKS OF
OPEN CALL TANT REFLECTING ACTIVE
GENE ACTIVITY AND YOU CAN SEE
THAT AT THIS END OF THE REGION,
THERE'S HUGE PEAKS FOR ENHANCER
EXPRESSION AND ENHANCER ACTIVITY
AND LOTS OF OPEN CHROME TIN
SHOWN BY THE DARKER BLACK BOXS
SO THIS NARROWED OUR SEARCH TO
THREE OF THESE NOVEL
AFRICAN-SPECIFIC VARIANTS THAT
MIGHT BE CAUSAL FOR THE
ASSOCIATION OF GSDMA.
WE USED PROMO TIVE CAPTURE HIGH
C DAN AND BETWEEN PROMOTERS AND
ENHANCERS THAT ARE FAR APART,
NOT IN THE SAME GENE.
THIS IS THE FIVE PRIME ENDS OF O
R&D L3 AND THE ENHANCER MARKS AT
THEN OF THE REGION AND WHAT WE
SHOW ARE THE PRO MOTOR REGION OF
GSDMA IS INTERACTING WITH TWO
DIFFERENT PIECES OF THIS REGION
AND BOTH OF WHICH KIND OF
OVERLAP THESE TWO RIGHT HERE.
AND THIS SNIP THAT I'M SHOWING
YOU HERE IS ONE OF THESE TWO
SNIPS.
WE THINK THIS STORY IS
COMPELLING THAT THESE NOVEL
AFRICAN AMERICAN VARIANTS ON
HAPLOTYPE 4 AND SOME OF THE
OTHERS BUT NOT AS COMMONLY AS
HAPLOTYPE 4 IS IN AN DISRUPTING
AN ENHANCER OR ACT RATE ISING AN
ENHANCER THAT INTERACTS WITH THE
PROMOTER OF GSDMA SO WE ASK
WHETHER THIS WAS ASSOCIATED WITH
ANY PARTICULAR PHENOTYPES IN
EUREKA AND TOGETHER WHAT WE SAW
WAS THAT THE GENE WHEEL WAS
ASSOCIATED WITH LOWER LUNG
FUNCTION, LOWER BLOOD COUNTS AND
LOWER IGE LEVELS IN THIS EUREKA
PLUS SPECIFIC OF AFRICAN
AMERICAN CHILDREN.
FINALLY, WE HAVE DATA IN AFRICAN
AMERICAN ADULTS BUT WE DIDN'T
HAVE FULL GENOME SEQUENCING SO
WE USED HAPLOTYPE 4 AS A SORROW
GET AND WE SAW A STRIKING
ASSOCIATION OF ASTHMA SEVERITY
IN ADULTS SO THESE ARE MILD,
MODERATE AND SEVERE AND CAN YOU
SEE THE FREQUENCY OF HAPLOTYPE 4
IS HIGHER THAN THE SEVERITY.
SO, THIS STUDY ADDS TO THE ON
GOING COMPLEXITY OF THE REGION
AND SHOWN THAT AFRICAN-SPECIFIC
CAN MONDAY FIE THE GWSA AND
ASTHMA SEVERITY AND BOTH GSDM
AND GSDMA OF THE AFRICAN
SPECIFIC HAPLOTYPE ARE SEVERE
ASTHMA AND WE HAVE A NUMBER OF
ON GOING STUDIES NOW TO FURTHER
CHARACTERIZE THE LONGITUDINAL
THEME EVENTS OF THESE VARIANTS.
SO NOW WE'LL SWITCH GEARS AND
TELL YOU A LITTLE BIT ABOUT A
STUDY THAT WE'VE JUST COMPLETED
ON LOOKING AT THE METH A LOAM
WHICH IS THE MARK THAT WE HAVE
STUDIED ALONG IN OUR LAB.
SO I THINK EVERYONE IS FAMILIAR
WITH THE CONCEPT THAT EPI
GENETICS IS THE LINK BETWEEN
ENVIRONMENT AND DOWNSTREAM
MOLECULAR RESPONSES AND THE
SHOWN ON THE CARTOON ON THE LEFT
AND IT CAN
RESULT IN HEALTH AND DISEASE
STATES DEPENDING ON WHETHER IT'S
POSITIVE OR NEGATIVE AND DNA IS
THE MOST COMMON EP GENETIC MARK
IN THE GENOME AND THE CPG IS
COMMON WITH MORE THAN 38 MILLION
CPGs THAT ARE POTENTIALLY
SUSCEPTIBLE TO THE MODIFICATION
AND DNA CAN CONTRIBUTE TO
DIRECTLY TO THE DISEASE RISK OR
BE INTERACTIONS AND RELATIVELY
LITTLE AS KNOWN ABOUT INTER
INDIVIDUAL AND VARIATION AND
IT'S REALLY PRIMARILY RELATED TO
THE CONTENT ON THE AND WE WERE
LUCKY IN THAT WE THOUGHT IT WAS
A IMPORTANT QUESTION TO PROVIDE
US WITH FUNDS TO DO THIS AND
WHAT WE DID WAS PERFORM A WHOLE
GENOME SEQUENCING STUDY AND
AIRWAY CELLS TO IDENTIFY
DIFFERENT REGIONS THROUGH OUT
GENOME WITHOUT ANY BIAS
SELECTION CRITERIA SO THERE WAS
AND WE PERFORMED THIS STUDY IN
20 EUROPEAN AMERICAN CHILDREN
FROM THE COAST COHORT AND
AFRICAN AMERICAN CHILDREN EUREKA
AND HALF OF THOSE CHILDREN IN
EACH HAD ASTHMA PLUS ALLERGIES
AND HALF HAD NO ASTHMA AND NO
ALLERGY AND WE LOST ONE SAMPLE
ALONG THE WAY.
WE IDENTIFIED CPGs AND WE
SELECTED THE CPGs THAT WOULD
BE THE MOST FUNCTIONAL AND
THEY'RE HIGH VALUE CPGs AND
WITH THESE WE TOOK ALL THE
CPGs AT REGIONS AND IT WAS
ABOUT 100,000 OF THOSE AND WE
TOOK ALL CPGs AT ASTHMA OR
EARLY GEE OR WITH DIFFERENTIAL
IN THE PREVIOUS ASTHMA ALLERGY
STUDY AND WE THEN FILTERED THOSE
CPGs FOR OVERLAP WITH AT LEAST
THREE DIFFERENT FUNCTIONAL
ANNOTATIONS SUCH AS PREDICTIVE
ENHANCERS, TRANSCRIPTION FACT
OWE BINDING SITES AND ET CETERA,
AND THEN WE EXCLUDED ANY CPG ON
THE RAY AND OVERLAPPED WITH
REGIONS THAT MADE INTERPRETATION
DIFFICULT AND THEN WE WORKED
WITH ALUM INA TO DESIGN A CUSTOM
ASTHMA ALLERGY AND THE IDEA IT
WOULD BE A 50,000CPG ARRAY THAT
WAS A BOOSTER TO THE EPIC ARRAY
AND THE CPGs AND AFTER
MANUFACTURE AND ALL THE OTHER
THINGS WE HAVE TO GO THROUGH AND
WE ENDED UP WITH ABOUT
38,000CPGs AND WE SHOULD BE
CLOSER TO 50K THEY THEN STUDY
AND THE PAPER DESCRIBING WHAT
I'M GOING TO TALK ABOUT HAS JUST
BEEN POSTED ON ARCHIVES AND
SUBMITTED FOR PUBLICATION AND SO
AS EXPECTED.
MOST OF THE CPGs OVERLAP WITH
ENHANCER MARK OR TRANSCRIPTION
FACTOR BIND SEWING 94% WITH THE
FIRST AND 90% WITH THE AT THE
AND SO THIS IS TELLING US VERY
DIFFERENT THAN WHAT GWAS TELLS
US IN ADDITION, THE CPGs ON
THE CUSTOMER ARRAY ARE ENRICH
FOR INTERMEDIATE CPGs AND
DEPLETED FOR HYPO METH OWE LATED
PCGs THAT'S S AND THAT'S BETA VH
IS THE PERCENT METHODDATION AT
EACH CPG SITE AND EACH NINE THIS
DENSITY PLOT IS AN INDIVIDUAL
AND THESE ARE THE SAME URECA AND
THERE ARE THESE HUGE PEAKS OF
CPGs THAT ARE HYPER METH OWE
LATED AND HYPO METH OWE LATED
REGION AND IN FACT, WHEN WHICH W
THIS WE WERE FIRST WORRIED THAT
SOMETHING WAS WRONG BUT WE
DEFLEET FOR THESE HIGH PER
METHYLATED REGIONS AND WE TOOK
THE CPGs ON THE EPIC AND PUT
THEM THROUGH THE SAME PIPELINE
THAT WE USED, AND IN DEED, WHEN
WE DO THAT, WE GET RID OF THE
EXTREMES AND WE ENRICH FOR INTER
MEDIATED METH A LATED CPGs AND
THEY'RE FILTERED EPIC CPGs ON
THE EPIC BUT THEY WERE THE ONES
THAT WERE THE PASS THROUGH THE
FILTER IF WE DIDN'T EXCLUDE THE
EPIC CPGs FROM OUR ARRAY.
OK, SO THEN, WE NEXT DID A WE
HAD THE PERCENT POSITIVE
SKIN-PRICK TEST OUT OF 14
AIRBORN OR ALL ALLERGENS AT AGE
10 AND THE EPITHELIAL CELLS WERE
COLLECTED AT AGE 11.
AND SO THIS IS THE RESULTS OF
THE EWAS AND LOOKING AT VOLCANO
PLOTS, THIS IS THE LONG 2 FOLD
CHANGE ON THE X AXIS AND THE
MINUS LONG 10P VALUE ON THE Y
AXIS AND CUSTOM IS ON THE BOTTOM
AND THESE ARE THE NUMBER OF
CPGs THAT WERE METH LATED OR
LESS METH LATED EVEN THOUGH
THERE ARE MORE BECAUSE THE ARRAY
IS SO MUCH LARGER, THERE'S AN
ENRICHMENT FOR DNC ON THE
CUSTOMER WHERE IT'S 5% WERE
DIFFERENTIAL COMPARED TO .2% ON
THE EPIC AND IN ADDITION, WE'RE
SHOWING IN PURPLE HERE, THE
CPGs ON THE FILTER EPIC AND
BLUE IS THE NON WHAT WE NOTED
WAS 16% OF THE EPIC DMCs ARE
FILTERED COMPARED TO 3.5% OF ALL
AND THE PIPELINE WE USE ENRICHED
FOR CPGs THAT ARE ASSOCIATED
WITH SENSITIZATION AND I WON'T
HAVE TIME TO SHOW YOU BUT WE
REPLICATED THESE RESULTS ON
CUSTOMER ARRAY AND THE INSPIRE
COHORT WHICH IS NUMBER CHILDREN
MUCH MORE WHITE AND MOVING IN
CENTRAL TENNESSEE AND SO THAT WE
KNOW NOW THAT THE ARRAY IS
ROBUST TO AGE RACE AND GEOGRAPHY
AND EVEN THOUGH THE DENSITY
PLOTS THAT I SHOWED IN THE
PREVIOUS SLIDE SHOWED BIG
DIFFERENCES BETWEEN THE EPIC IN
CUSTOM AWAY IF WE DO THE DENSITY
PLOTS FOR THE CPGs THEY WERE
NEARLY IDENTICAL SO AGAIN, THIS
IS REINFORCING THE IDEA THAT
INTERMEDIATE LEVEL METHYLATION
ARE THE CPGs THAT ARE REALLY
THE ONES THAT ARE ASSOCIATED
WITH PHENOTYPES.
WE ALSO ASKED, ARE THEY ALSO
MORE LIKELY TO BE ASSOCIATED
WITH THE EXPRESSION OF NEARBY
GENES AND THE ANSWER TO THAT IS
YES.
AND SO FOR BOTH ARRAYS, THE IF
YOU JUST LOOK AT THOSE
CORRELATED AND BETWEEN THE CPG
METHYLATION LEVELS AND THE
EXPRESSION OF THE GENE.
AND THE OTHER LAST THING THAT
I'LL MENTION IS THAT VERY
STRIKING PATTERN OF ASSOCIATION
DIFFER IT'S A THE CPGs ON SO
VERSUS A TYPICAL RESULT THAT YOU
SEE ON THE EPIC AND IT'S A LOW
SYSTEM PLOT BUT I'M PLOTTING THE
CPGs AND THE P VALUES FOR THE
DIFFERENTIAL METHYLATION LOT
ASSOCIATION.
AND HERE, THERE'S A SINGLE CPG
ON THE EPIC ARRAY THAT IS
METHYLATED IN THE CENTERING IT'S
A NICE CANDIDATE WITH VERY
LITTLE SUPPORTING EVIDENCE FROM
OTHER CPGs SHOWN IN BLUE AND
AND THEY'RE NOT SIGNIFICANT AT
ALL AND THE TWO DIFFERENCE MINDS
ARE SHOWING 5% FDR AND EPIC AND
THE CUSTOM AND WE DIDN'T CHERRY
PICK THIS RESULT OF TOP 10 MOST
SIGNIFICANT CPGs AND AND EIGHT
OF THE 10 WAS NOT FROM THE NON
FILTER AND THIS IS A TYPICAL
RESULT THAT WE THE SPIKES OF
ASSOCIATION AND ON THE EPIC AND
THE INSPIRE AND ON THE CUSTOM
AND EUREKA AND WE HAVE SUPPORT
WHERE THERE'S BOTH FILTER EPIC
AND NON FILTER EPIC IN THIS SAME
AND THIS WEEK IS IN THE EX ON WE
SAW SHOWN ON THE X AXIS AND AND
WHEN WE LOOK AT THE RELATIONSHIP
BETWEEN INCREASING METHYLATION
YOU CAN SEE THAT THE MORE
METHYLATED THIS LOCUS THE FEWER
HIGHEST EXPRESSERS OF THIS GENE.
THIS IS A NEGATIVE REGULATORS OF
SIGNALING IN PREVIOUS STUDIES
AND INCREASE EXPRESSION OF MRNA
AND CELLS AND IN THIS ONE PAPER
IT WAS SUGGESTED AS PROTECTION
ASTHMA AND THESE ARE BOTH
CONSISTENT WITH OUR RESULTS AND
WHICH FURTHER SUGGEST THAT THE
ASSOCIATED WITH ALLERGIC
SENSITIZATION AND IT'S NOTABLE
TO ME, THAT THIS GENE IS NOT AT
AN ASTHMA OR ALLERGY GWAS LOCUS
IS SUGGESTING THAT EPI GENETIC
MODIFICATION REFLECTS RESPONSE
TO EXPOSURES OR GENE ENVIRONMENT
INTERACTIONS AND IT CLEARLY
DOESN'T HAVE A MAIN GENETIC
SIGNAL THAT IS DRIVING THIS
PHENOTYPE SO TO WRAP 2 HAS A
RESOURCE FOR INTEGRATED STUDIES
ON THE DEVELOPMENT OF ASTHMA AND
LEADING TO THE DISCOVERY OF
CAUSAL VARIANTS AND GENES OF THE
MOST IMPORTANT CHILDHOOD SOME
SPECIFIC TO CHILDREN OF AFRICAN
ANCESTRY AND SIGNATURE OF HIGH
FALL FUNCTION CPGs AND THEIR
ROLE IN MEDIATING THE EFFECTS OF
ENVIRONMENTAL EXPOSURES ON ALERT
DESENSITIZATION AND OTHER HEALTH
OUTCOMES.
OUR ULTIMATE GOALS IS TO
IDENTIFY NEW DRUG TARGETS OR
PREVENTATIVE STRATEGIES TO
REDUCE THE INI GRAVE A HUGE
THANKS TO THE URECA
INVESTIGATORS AND IT'S AN HONOR
BEING INVITED AND THEY
DELIBERATELY DID EVERYTHING AND
I'LL GET TO CHARLES IS THE
GRADUATE STUDENT WHO WORKED ON
THE MAPPING STUDIES AND AND SO
HE IS REALLY OVERSEEING ALL OF
THESE STUDIES THAT I'VE
DESCRIBED TODAY.
AT THIS FOR YOUR ATTENTION.
THANK YOU, CAROLE, THAT WAS
FANTASTIC.
WE CAN PROBABLY TAKE ONE OR TWO
QUICK QUESTIONS AND THEN AGAIN
WE CAN TRY TO TAKE ANYMORE AT
THE END IF THERE ARE UNANSWERED
OR UNADDRESSED.
SO PLEASE FEEL FREE TO JUMP OUT
OR STICK YOUR HAND UP, WHATEVER
IS EASIEST.
I FOUND IT WAS TOWARDS THE END
THERE, WHEN YOU WERE SHOWING THE
DIFFERENCE IN IDENTIFICATION OF
SITE BY THE EPIC ARRAY VERSUS
THE CUSTOM ARRAY AND WHEN IT'S
ON THE IT'S A FEATURE OF HOW YOU
DESIGNED YOUR ARRAY VERSUS EPIC
ARRAY WOULD IT MAKE SENSE TO
HAVE EVERYTHING YOU IDENTIFIED
BY THE WHOLE GENOME BY WHOLE
FACE SEQUENCING ON THE EPIC
ARRAY GOUGH THROUGH THE SAME
PROCESS SO YOU HAVE THE REGION
AROUND THAT CPG OR IS THAT
UNNECESSARY?
>> SO, THAT IS, I AGREE WITH
THAT AND IN FACT MOST OF THE
SIGNALS THAT WERE PICKED UP BY
THE EPIC DON'T HAVE ANY CUSTOM
ARRAY AND WITHOUT REALIZING IT
AROUND CLUSTERED AROUND GENES SO
WE DON'T COVER AS MUCH SCOPE AS
THE EPIC RESULTS THEY'RE REALLY
SPREAD OUT.
>> HAVE YOU BEEN ABLE TO START
TO LOOK AT WHETHER THERE'S ANY
CLINICAL ASSOCIATIONS EITHER
BASED ON THE INDIVIDUALS
PHENOTYPE OR THE ENVIRONMENT
THAT ARE ASSOCIATED WITH THE
EPIGENETIC MODERATIONS THAT YOU
ARE SEEING?
>> WELL, DO YOU KNOW WHAT I
MEAN?
ARE THERE FEATURES SO PETS OR
ANYTHING LIKE THAT?
>> THAT'S A PROJECT TO LOOK AT
ALL THE ENVIRONMENTAL EXPOSURES
AND EUREKA BUT WE HAVE SOME
RESULTS ON POLLUTION WHICH I
DIDN'T HAVE TIME TO GO INTO BUT
I FORGOT TO TAKE IT OUT OF THE
SLIDE AND THERE ARE PREVIOUSLY
STUDIES THAT SUGGESTED THAT
INTERMEDIATE CPGs ARE THE ONES
THAT ARE REALLY RESPONSIVE TO
ENVIRONMENTAL STIMULUS.
AND IN OUR POLLUTION STUDIES
WE'RE SUPPORTING THAT AND IT'S
VERY PRELIMINARY SO I DIDN'T
WANT TO PRESENT THEM YET AND
THERE'S AND EXPOSURE IN WE'RE
EXCITE TODAY DO IN URECA BECAUSE
THEY HAVE A LOT OF ENVIRONMENTAL
EXPOSURES AND EVEN LIKE STRESS
AND ALL THE THINGS THAT SEEM TO
BE ASSOCIATED WITH DIFFERENT
ASTHMA PHENOTYPES WE'LL LOOK AT
WITH RESPECT TO THESE USING THE
ARRAY AND TO SEE IF WE CAN
ACTUALLY PARSE OUT THE EFFECTS
OF GENES VERSUS ENVIRONMENT ON
THE DNA METHYLATION LANDSCAPE.
>> EXCELLENT.
>> IT'S A GREAT QUESTION.
WE HAVEN'T DONE IT YET.
>> I HAVE A COUPLE OF QUESTIONS
BUT IF THERE'S TIME.
>> OK.
>> IF YOU ARE OK WITH THAT,
WE'LL TURN THINGS OVER TO MATT.
>> HE WILL SHOW SOME OF HIS DATA
ON THE TRANSCRIPTIONAL
SIGNATURES IN THIS POPULATION.
>> I HAVE MY SCREEN HERE.
YEAH, I JUST SAID ALSO VERY
HONORED TO BE INVITED.
I'VE NOT JOINED ONE OF THESE
SESSIONS BEFORE AND IT'S BEEN A
VERY INTERESTING DAY AND ALWAYS
HAPPY TO TALK ABOUT THE URECA
DATA AND ALWAYS INTERESTING TO
FOLLOW AFTER JIM AND CAROLE, WHO
HAVE SUCH AN OUTSTANDING DATA
AND HOPEFULLY WHAT I'LL SHOW
HERE IS A LITTLE MORE ONE OR TWO
STORIES BUT A NICE ADDITION
ABOUT WHAT WE HEARD ABOUT THE
UCECA COHORT.
I'M GOING TO TALK ABOUT AIRWAY
EPITHELIUM GENE EXPRESSION END
OWE TYPING OF MASS AND RHINITIS
IN URBAN CHILDREN.
THIS IS A QUICK REMINDER, THE
URECA BIRTH COHORT THE IDEA THAT
YOU KNOW, THERE'S JUST GREAT
DETAIL ABOUT FACTOR FROM
PRE-NATAL AND THROUGH NOW
TEENAGE YEARS OF RISK FACTORS
FORT DEVELOPMENT OF DISEASE AND
ALL OF THAT IS FACT ORDER INTO
THESE ANALYSIS AND WHAT I'M
SPECIFICALLY GOING TO TALK ABOUT
THIS IS LOOK AT THE AGE 10 AND
11 TIME POINT WHEN THIS VERY
DETAILED FINE OWE TYPING WAS
DONE AROUND RESPIRATORY
PHENOTYPES AND RHINITIS FI
PHENOTYPES AND LOOKING AT
SAMPLES FROM THE UPPER AIRWAY
AND USED FOR RNA SEQUENCING
ANALYSIS.
SO, AGAIN, REMINDER THAT USING
THIS CLUSTERING METHOD, THERE
WERE SIX FINE OWE TYPES THAT
DELL OVER THE FIRST 10 YEARS OF
LIFE AND BASED ONTHIS IS THE
MOST SEVERE GROUP BEING
RELATIVELY SEVERE ALLERGIC
ASTHMA AND WHERE WE SEE THIS
LOSS OF FUNCTION AND THIS MEDIUM
FLOW GROUP AS SOMETHING MORE OF
A NON OR AT LEAST A LOW ALLERGY
AMA GROUP.
THIS SLIDE IS KIND OF A STAND-IN
NOR THE METHODOLOGY THAT I'LL
DESCRIBE HERE BASICALLY AND USED
FOR HOST MRNA SEQUENCING AND
THIS TABLE IS THE SHOW THAT WE
HAD GOOD SAMPLE SIZE AND FAIRLY
SEEK DISTRIBUTION ACROSS THE SIX
PHENOTYPES OF INTEREST AND THE
METHOD WE USED FOR THOSE WHO ARE
FAMILIAR WITH AND SOMETHING LIKE
A TRANSRIPTOME DATA SET IT'S
NICE TO USE A NETWORK ANALYSIS
TYPE APPROACH TO REDUCE THE
DIMENSIONALITY OF THE DATA AND
INFUR COHERENT BIOLOGY AND WE
USED THIS WGCNA NETWORK ANALYSIS
AND TO PURELY DATA DRIVEN
FASHION AND COLLAPSE CORRELATED
GENES INTO NETWORKS AND WHILE WE
CALL MODULES SO 26 DISTINCT
MODULES WHICH REPRESENT
DIFFERENT BOYOLOGY AND DIFFERENT
PATTERNS OF THE DATA AND WE CAN
THEN USED TO MODEL FOR OUR
QUESTIONS OF INTEREST AND SO,
LINEAR MODELING, ASKING
DIFFERENCES BY GROUP OR RELATING
A MODULE TO LUNG FUNCTION OR
OTHER CONTINUOUS VARIABLES AND
WE CAN ADJUST THESE FOR THINGS
LIKE CELL FREQUENCY OR CLINICAL
SITES AND TO ULTIMATELY COME AT
SPECIFICALLY IMPORTANT
DIFFERENCES THAT EXIST.
I'LL START WITH THIS COMPLICATED
HEAT MAP WHICH IS MEANT AS A
GLOBAL OVERVIEW OF THE MANY
SIGNALS THAT EXIST DESCRIBING
THESE DIFFERENT PHENOTYPES AND
I'LL FOCUS ON A FEW OF INTEREST
AND SO HERE WHAT I'M IN EFFECT
SHOWING IS A GROUP LEVEL
EXPRESSION OF EACH OF THESE 26
MODULES EACH ROW IS THESE SCORES
SO NORMALIZED SHOWING THE
RELATIVE DIFFERENCE AND
EXPRESSION A CROSS THE GROUPS
AND ONE OF THE FIRST HEAT MAPS
ARE TRICKY TO READ BUT ONE OF
THE OBVIOUS FINDINGS AND AS I
LABEL THE BOTTOM, THEY ARE IS A
CLEAR DICHOTOMIATION AND I HAVE
INCREASING WHEEZE FREQUENCY AND
WITH LOW ATP ON THE LEFT AND
HIGH ATP ON THE RIGHT AND LOW
ATP AND IT'S CLEAR THERE ARE
BLOCKS AND FOR EXAMPLE IN THAT
HIGH WHEEZE HIGH ATP LOW
FUNCTION GROUP AND AND THE
MEDIUM WHEEZE LOW ATP AND I'LL
SHOW YOU KEY BIOLOGIC RESULTS
IRRELEVANT TO EACH OF THOSE.
SO ACTUALLY FIRST LET ME DISCUSS
ONE EXAMPLE AND SHOULD BE A GOOD
GROUNDING BY BIOLOGIC GROUNDING
IN DISTINGUISHES AND GROUPS FROM
LOW ATP GROUPS AND THIS IS TH2
AND ILC2 AND THE REASON FOR THIS
IS THAT CONTAINS GENES OF COURSE
VERY MUCH AND FUNCTIONS OF THEM
SO IT INCLUDES FOR EXAMPLE, THIS
IS A GENE-GENE NETWORK PLOT
SHOWING THE CORE GENES SO IL13
AND IL1 WHICH IS ST2 THE
RECEPTORS FOR IL33 AND OTHERS
ARE FAIRLY SPECIFIC TO THOSE TWO
CELL TYPES AND WHAT WE CAN SEE
HERE IS THAT THE NOW RATHER THAN
SHOWING THIS HEAT MAP SCORE YOU
CAN SEE THE DISTRIBUTION OF THE
DATA BY BOX PLOT AND THE REASON
THAT THIS IS SIGNIFICANT, IS
BECAUSE OF THE THE DIFFERENCE OF
OBSERVED HIGH AND LOW ATM WITHIN
EACH OF THOSE AND SO, THAT WILL
BE SOMEWHAT IN CONTRAST TO THIS
NEXT EXAMPLE WHERE WE PICK UP A
NUMBER OF PATHWAYS RELATIVELY
SPECIFIC IN ONE MANNER OR
ANOTHER AND SO THE HIGH WHEEZE
HIGH ATP LOSS OF LUNG FUNCTION
GROUP.
>> ONE ADDITIONAL ONE SHOWED THE
GRAPHICAL ABSTRACT AND BUT NOW
SHOWING A MODULE THAT IS
SPECIFICALLY ELEVATED WITHIN A
HIGH WHEEZE HIGH ATOPY LOSS OF
FUNCTION GROUP AND THIS IS A
MUCUS HYPER SECRETION PATHWAY
AND YOU CAN SEE THE CORE BIOLOGY
HERE IN THIS NETWORK BUT NOT
ONLY THE EFFECTER GENE ITSELF
BUT THE LIFE OWE SIM AND OTHER
PROTEINS FOX A3 CRITICAL TRANS
DESCRIPTION FACTOR AND TF F-1, 2
AND 3 OF THE MUCUS LAYER AND
HERE AGAIN WE SEE THIS
RELATIONSHIP TO LUNG FUNCTION
AND PULLED THIS OUT OF THE
RELATIVELY UNIQUE ASPECT TO
THOSE INDIVIDUALS WITH IMPAIRED
DEVELOPMENT OF LUNG FUNCTION.
THIS WAS ALL PUBLISHED IN ONE
PAPER IN JACI A YEAR AGO AND WE
ACTUALLY EXTENDED THIS WORK WE
WANTED TO LOOK AT GENE BY TEEN
EXPRESSION RELATIONSHIP SO USING
GENOTYPES FROM THAT RNA
SEQUENCING DATA WE HAVE THE GNA
SEAT DATA FROM CAROLE AND WE'VE
BEEN ABLE TO SEE A NUMBER OF
SNIPS WITHIN THE MUC5AC AS BEING
RELATED TO THE LEVEL OF
EXPRESSION SO THIS IS AN EQTL
ANALYSIS AND IN FACT, IT'S HARD
TO APPRECIATE FROM THIS LD PLOT
ON THE BOTTOM, BUT FUNDAMENTALLY
THERE ARE TWO DISTINCT LD
LIBERALS WITHIN MUC5AC AND EACH
OF WHICH HAVE A SIGNIFICANT
RELATIONSHIP TO THE LEVEL OF
MUC5A EXPRESSION IN THE URECA
CHILDREN AND THIS ONE ON THE
LEFT BEING QUOTE-UNQUOTE DELL
TIER YUS AND ASSOCIATED WITH
HIGHER EXPRESSION MUC5LA AND
PROTECTED YOU WOULD SAY WERE THE
REVERSE HERE AND RELATES TO
LOWER AND I DON'T SHOW IT BUT
WHEN YOU LOCK AT THEM TOGETHER
THE COMBINATION OF THE TWO AND
HAVE A ADDITIVE EFFECT ON THE
DEGREE OF EXPRESSION AND ONE
NICE THING BECAUSE WE HAVE THE
RNA SEQUENCING WE CAN RUN ANNA
LEGAL SPECIFIC EXPRESSION AS
WELL AND SEE IN DEED IN THOSE
WHO ARE -- WHO HAVE BOTH ALLELE
WE SEE HIGHER EXPRESSIONS OF THE
ALLELE ASSOCIATED GREATER
EXPRESSION IN THE ANALYSIS AND
JUST TO DIVERGE AND ONE NICE
THING THAT WE WERE ABLE TO DO
AND THIS IS LEVERAGING ICAC TO
CAUSE THIS AND ANOTHER
POPULATION AND THIS WAS THE
COHORT AND WITH ESTABLISHED
RELATIVELY SEVERE EXACERBATION
PRONE AR MASS AND WE WERE ABLE
TO LOOK AT THOSE GENOTYPES IN
RELATION TO MUC5A EXPRESSION AND
PARTICULARLY DURING RESPIRATORY
ILLNESS AND WHAT THIS SHOWED US
WAS THAT IN FACT THESE SNIPS
HAVE AN INDEASE ABLE E DUCE ABLG
EXACERBATION IN PARTICULAR, WE
SEE A GREATER DEGREE OF UP
REGULATION OF THIS IN THE
EFFECTED GENOTYPE AND THE FINAL
FINDINGS JUST CIRCLEELING BACK
TO MY EARLIER DEMONSTRATION OF
THE
AND THIS IS A VARIABLE AGES FOR
THE COHORT BUT THIS ALLELE
HAVING A DIRECT RELATION TO LUNG
FUNCTION AS WELL.
I WILL NOW RETURN TO THE STORY I
STARTED AND WHICH WAS THIS END
OWE TYPING OF THE UREKA COHORT
AND I SHOWED YOU THE PATHWAYS TO
THE LOW FUNCTION GROUP AND LET
ME SPEND IF THE MINUTE ON THE
MEDIUM WHICH AGAIN I SAID AT THE
OUTSET RESEMBLED A LOW NON A
TOPIC ASTHMA AND WE CAN SEE IF
YOU JUST LOOK GLOBALLY THERE'S A
DISTINCT PATTERN AND THE SIGNALS
IN THIS GROUP ARE CERTAINLY A
LITTLE BIT WEAKER OR A LITTLE
BIT MORE HETEROGENEOUS BUT A FEW
AND ONE BEING THAT THIS AND
RELATIVE AND LOWER EXPRESSION OF
AN INTEGRITY AND LUKE OWE SIGHT
MIGRATION PATHWAY AND PATHWAY IN
WHICH CAR TIN AND SIMILAR AND
RELATIVE OVER EXPRESSION OF THIS
INJURY RESPONSE PATHWAY AND
INCLUDING SIGNALING AND A COUPLE
OF OTHER SIGNALING PATHWAYS.
SO A HIGH WHEEZE GROUP AND WE
CAN SEE HERE IN A NETWORK OF
NETWORKS WHERE WE LINK IN THE
RELATIVE ASSOCIATION OF THE
DIFFERENT PATHWAYS WE
IDENTIFIED.
YOU CAN SEE AT A BROAD SCALE THE
MULTIPLE THINGS THAT ARE OVER
EXPRESSED AND HIGH WHEEZE HIGH A
TP LOSS OF LUNG FUNCTION
INCLUSIVE THE TWO I SHOWED AND
TWO OTHERS AND OTHERS YOU CAN
SEE HERE.
AND AGAIN A VERY DIFFERENT STORY
IN THE MEDIUM WITH LOW ATP OF
THE TWO I TALKED ABOUT AND ALSO
RELATIVE IMPAIRMENT OF AN ANTI
OXIDANT GENE EXPRESSION PATHWAY
AND I'LL TURN IT TO ONE ON GOING
PROJECT WHICH IS WORKING WITH
JIM THE CHARACTERIZATION NOW OF
RHINITIS PHENOTYPES IN THESE
CHILDREN AND SO JIM SHOWED THIS
USING THE SAME PORT OF METHOD OF
THE CHILDREN CAN BE GROUPED BY
THEIR 11 YEAR TRAJECTORY OF
UPPER AIRWAY SYMPTOMS AS EITHER
THOSE WITH PERSISTENT DISEASE
FROM EARLY LIFE AND THOSE WITH
DECREASING INCREASING AND THOSE
WITH RELATIVELY LOW SYMPTOMS AND
WE CAN APPLY THE SAME SORT OF
SEEK ANALYSIS AND IN FACT WE CAN
APPLY THE SAME MODULES WE HAD
IDENTIFIED AND THIS IS ON GOING
SO WHY WANT TO GET TO INTO IT
BUT NOTICE A NUMBER OF PATHWAYS
RELEVANT TO EACH OF THESE ONE
THING THAT STOOD OUT
IMMEDIATELY, EXCUSE ME, IS THAT
THIS EARLY PERSISTENT RHINITIS
PHENOTYPE SEEMS TO STAND OUT IN
THEIR RELATIVE LOW EXPRESSION OF
A VARIETY OF LET'S CALL THEM
ANTIMICROBIAL PLUS INNATE AND
ADAPTIVE IMMUNE RESPONSE
PATHWAYS AS OPPOSED TO STANDING
OUT TYPE 2 INFLAMMATION.
WITH THAT I'LL CONCLUDE.
I GUESS I SHOULD ACTUALLY SAY
ABOVE ALL THIS THAT BASICALLY
THE USE OF IN PARTICULAR AIRWAY
PROFILING HAS BEEN EXTREMELY
VALUABLE AND UNDERSTANDING THE
ACTUAL BIOLOGY BEHIND THE VERY
NICE CLINICAL TRAJECTORIES AND
WE'VE SEEN SIGNALS IN BLOOD AS
WELL AND SORT OF AS CAROLE
ALLUDED TO ITS NOT QUITE AS
VALUES ABLE AS LOOKING AT THE
TARGET ORGAN.
BUT HERE, WITHIN YOUR URECA,
WE'VE SEEN SPECIFIC MOTH HE CAN
YOU LAR PATHWAYS AND MAUD USE BY
PHENOTYPE AND MAUD USE QUITE A
FEW MODULE INCREASED IN THIS
HIGH WHEEZE HIGH LOSS OF LUNG
FUNCTION INCLUSIVE OF THE ONES I
LISTED HERE AND A DECREASE IN
ASPECTS OF INNATE IMMUNITY AND
COMBINING AND LEVERAGING THE
EXPERTISE OF CAROLE AND HER
GROUP LOOKING AT GENETIC
VARIANTS AND ALLOWED US TO
IDENTIFY A FAIRLY IMPORTANT
VARIANT IN THE MUC5AC AND
ASSOCIATING WITH GENE EXPRESSION
AND GAINING IN SIGHT INTO THIS
GROUP WHERE WE SEE INCREASES EGF
AN RELATIVE DECREASE IN
INTEGRITY AND LUKE OWE SIGHT
MIGRATION OF ACTIVITY ACTIVATION
PATHWAYS.
WITH THAT I'LL CONCLUDE SUPPORT
FROM NIAID AND PARTICULAR AND
JIM OF THE WHOLE GROUP AT
MADISON WHO HAVE RUN ICCAC AND
CAUSE AND SCOTT IN MY GROUP WHO
CONTRIBUTED A LOT TO THESE
ANALYSIS AND STUDENT AND WHO IS
WORKING ON THE RHINITIS DATA AND
THE INVESTIGATORS AND EUREKA
STUDY FAMILIAR LOOSE WHO HAVE
BEEN DOING THIS FOR SO MANY
YEARS.
WITH THAT I'LL END AND TAKE ANY
QUESTIONS.
>> QUESTIONS FOR MATT ON THAT
I'M REALLY INTERESTED TO SEE HOW
THE RHINITIS PHENOTYPE SHAPOUS
AND BETWEEN THE END OWE TYPES
FOR THE POPULATIONS THERE VERSUS
THE OS MOW PHENOTYPES?
>> THIS IS HOT OFF THE PRESS
YEAH, I THINK WE HAD A MEETING
THAT WAS GOING TO BE THIS WEEK
IT'S DELAYED A WEEK OR SOMETHING
BUT EVERYBODY CAN PUT THIS
TOGETHER AND I HAVE NOT
PERSONALLY SEEN THE OVERLAP OF
THE RHINITIS PHONE OWE TYPES BY
RESPIRATORY PHONE OWE TYPES THAT
WOULD BE TRANSRIPTOME.
>> I JUST HAVE A QUICK COMMENT
IT WILL TAKE TOO MUCH TIME TO
DISCUSS I HAD QUESTIONS FOR BOTH
CAROLE AND MATT BUT I'M VERY
INTERESTED IN THIS FINDINGS WITH
NISH AND THEN, IN MATT'S DATA I
ALSO SEE AM A IT'S A COMMENT AND
OUR COLLEAGUES HERE HAVE JUST
HAVE ISSUES A FEW MONTHS AGO IN
SCIENCING MACROPHAGES AND
HOMEOSTATIC FUNCTION IS
REGULATED WHICH CON STRAINS CYTO
SIGN EXPRESSION AS RISK TO
EXPRESSION AND I DON'T KNOW
WHETHER THERE'S A PARALLEL IN
THE FEMALE CELLS AND THAT IS
SOMETHING THAT COULD BE LOOKED
AT AND I WAS JUST WONDERING EVEN
IF YOUR WORLD QUICK SORT OF
LOOKS HAVE YOU SEEN ANY INVERSE
RELATIONSHIP BETWEEN THE TWO?
>> IT'S A GOOD QUESTION AND I'LL
SAY A WORD OR TWO AND I NOTICE
THAT ALSO AND SOMETIMES IT'S
GOOD TO HEAR OURSELVES PRESENT
TO ONE ANOTHER AND I SAW THAT
ASSOCIATION AS WELL AND WE HAVE
NOT DONE A LOT OF WORK LOOKING
AT FOR EXAMPLE HOW TWO GENES ARE
TOO MUCH AND WE'LL ASSOCIATE
WITH ONE ANOTHER SO THAT USEFUL
TO DO WITHIN THE FRAMEWORK AND
I'LL SAY YOU KNOW THIS IDEA OF
CAROLE HAS DONE THIS SORT OF
GENOME WIDE WITHIN THE WE'RE
EQUAL A COHORT AND MINING THAT
FOR ASSOCIATIONS AMONG TWO GENES
OR CANNING VALUABLE SO I CAN'T
ANSWER THE BIOLOGY YOU ARE
ASKING THERE AND WE SHOULD
PRIORITIZE BUT THIS DATA SET AND
FRAMEWORK ALLOWS US TO LOOK AT
THAT LEFT OF DETAILS AMONG
GENES.
AND MY BRIEF QUESTION I'LL ASK
YOU THIS NOT ENOUGH TIME, HAVE
YOU SEEN THIS IS SOMETHING WE
HAVE SEEN IN THE COHORT IN
SEVERE ASTHMA WE'RE SEEING IT
AND A VERY INTERESTING
RELATIONSHIP BETWEEN HIS TMP AND
TYPE ONE ASK TYPE TWO INTER
NEURONS AND HAVE YOU SEEN THAT
IN YOUR DATA AT ALL?
>> INCLUDING THE T CELLS IF.
>> I DON'T THINK WE'VE LOOKED AT
THAT RELATIONSHIP IN OUR DATA.
WORE SEEING AN OPPOSITE
EFFECTOR?
>> IT'S POSITIVE RELATIONSHIP.
>> YEAH, THIS IS NOT A TH2
FOCUS.
>> YEAH, EXACTLY.
>> IT'S VERY INTRIGUING.
>> I WOULD BE INTERESTED TO TALK
MORE.
>> YEAH.
SAME HERE.
>> ANY OTHER FINAL QUESTIONS I
THINK WE'RE JUST ABOUT AT THE
TIME WE WERE ALLOTTED.
BUT IF THERE'S ANY ADDITIONAL
QUESTIONS, PLEASE POP YOUR HAND
UP OR JUST SPEAK OUT.
IF NOT I WANT TO THANK YOU THE
THREE OF YOU AGAIN FOR REALLY
GREAT TALKS.
IT WAS A WONDERFUL ADDITION TO
COUNCIL THIS AFTERNOON.
AND I THINK WE'LL TURN THINGS
BACK OVER TO YOU.
>> GREAT.
THANK YOU.
PATRICE AND THANK YOU CAROLE,
JENN AND MATT FOR THOSE
PRESENTATION AND KEEPING US ON
TIME.
WE HAVE FOUR CONCEPT CLEARANCES
FOR DISCUSSION AND CONSIDERATION
BY COUNCIL AND WE'LL START WITH
THE FIRST OF THOSE IS CHAO JIANG
WILL PRESENT THE CONFERENCE
CLEARING ON HUMAN IMMUNOLOGY.
I SEE YOUR SLIDES BUT I DON'T
HEAR YOU.
POSSIBLE YOU ARE ON MUTE.
>> HI, JOE, I'M MUTED BUT WE'RE
STILL NOT GETTING SOUND RIGHT
NOW.
ARE YOU USING A HEADSET?
CHECK YOUR AUDIO SETTING ON THE
BOTTOM LEFT.
>> WE'RE STILL NOT HEARING YOU.
OK.
>> THAT'S GOOD.
WE CAN SEE YOU NOW BUT WE ONLY
GOT SOUND FOR A FEW MOMENTS.
CAN YOU HEAR ME NOW?
>> YES, GREAT.
I'M GOING TO RESUME AND SHARE
THE SCREEN AND SORRY ABOUT THE
TICK UP.
>> THANK YOU.
>> SORRY ABOUT THAT.
AND GOOD AFTERNOON.
MY NAME CHAO AND I'M A PROGRAM
OFFICER IN THE BASIC IMMUNOLOGY
BRANCH AND TODAY I WILL TALK
ABOUT THE RENEWAL OF COOPERATED
CENTERS OF HUMAN IMMUNOLOGY OF
PCHI.
IT HAS BEEN RENEWED THREE TIMES
AND THE CURRENT FAMILY CYCLE
STARTED IN 2019 AND CCHI IS
DESIGNED TO SUPPORT MECHANISTIC
AND HYPOTHESIS TESTING STUDIES
AND TO UNDERSTAND HUMAN IMMUNE
RESPONSES TO INFECTION AND THE
PROGRAM SUPPORTS THE CENTRALIZED
INFRASTRUCTURE TO COORDINATE
MULTI-DISCIPLINARY RESEARCH AND
THE DEVELOPMENT AND APPLICATIONS
OF INNOVATIVE TECHNOLOGIES AND
THE PROMOTING PUBLIC DATA
ACCESS.
SO THE CURRENT FUNDING MECHANISM
IS U19 CO-OPERATIVE AGREEMENT
AND WE HAVE EIGHT ACTIVE AWARDS
NOW AND THESE STUDIES COVERED A
BROAD SPECTRUM OF HUMAN IMMUNE
RESPONSES AND TO INFECTIONS,
VACCINES AND IMMUNO
THERAPEUTICS.
SO, IN THE PAST THROW YEARS,
OVER 300 PEER REVIEWED
PUBLICATIONS HAVE BEEN
ATTRIBUTED TO THE CCHI PROGRAM
AND SOME RESEARCH HIGHLIGHTS ARE
SHOWN ON THIS SLIDE.
YOU CAN TELL THEY IDENTIFY NEW
CELL POPULATIONS AND NEW
MECHANISMS OF IMMUNE REGULATION
AND SO WHEN COVID-19 PANDEMIC
HIT IN 2020, WHICH WAS BUILDING
THE FIRST YEAR OF THESE U19
AWARDS, ALL THE CC HI CENTERS
QUICKLY PIVOTED THEIR RESEARCH
TO THE COVID STUDIES WITH THE
DISCIPLINARY INFRASTRUCTURE AND
SO HE IS PHYSICAL INDICATED
TECHNOLOGIES IN PLACE,
CCHI/PIs HAVE BEEN HIGHLY
PRODUCTIVE AND MADE A
CONTRIBUTION TO THE FUNDAMENTAL
UNDERSTANDING OF COVID-19
IMMUNITY.
SO IN TERMS OF TECHNOLOGY
DEVELOPMENT, CCHI SUPPORTED THE
APPLICATIONS AND THE FURTHER
DEVELOPMENT OF TISSUE IMAGING
TECHNOLOGIES AND THE CRUSTER
BASED TCR REP TO BE ANALYSIS
TOOLS.
SPACIAL TRANSCRIPT TOMICS HAVE
SINGLE CELL SEQUENCING TO
IDENTIFY SPATIALLY SEPARATED
COMPARTMENTS IN TISSUE AND
SEVERAL X VIVO PLATFORMS TO
STUDY HUMAN IMMUNE RESPONSES,
HAVE ALSO BEEN DEVELOPED SUCH AS
STANFORD HUMAN COUNCIL ORGANOIDS
THAT RECAPITULATE FEATURES IN
VITRO AND LABS AT A CULTURE OF
HUMAN LUNG TISSUE AND THE 3D
FILE PRINTING OF BREATH ABLE
LONG MODEL THOSE ARE GREAT TOOLS
FOR STUDYING THE INTERACTIONS
BETWEEN IMMUNE CELLS AND ALLOW
EPITHELIUM POST INFECTION AND
THE VACCINATION.
IT'S TRAINING SERVICES TO
BENEFIT ALL LABORATORY WITHIN
THE KNELT WORK.
HERE ARE PAPERS BY THE CCHIPI
AND IDENTIFIED OF PEER
EXPRESSING REGULATORY CDAP AND
RYE MODELING O OF THE INNATE
IMMUNITY IN RESPONSE TO
INFLUENZA VACCINES.
IS THE IMMUNE SARS-CoV-2 BY
THE LA JOLLA GROUP THAT SHOWED
CROSS REACTIVE IMMUNE MEMORY
UNEXPOSED TO HEALTHY PEOPLE WE
DO WE CONTINUE THE CCHI PROGRAM.
MANY KNOWLEDGE GAPS STILL EXIST.
WE HAVE OUR LARGE BODY OF DATA
USING THE SYSTEM BIOLOGY
APPROACH.
IT'S CHALLENGING TO EXTRACT
KNOWLEDGE FROM THESE DATA AND
TRANSLATE THEM INTO BETTER
UNDERSTANDING OF IMMUNE
MECHANISMS.
THEREFORE, WE THINK IT'S
IMPORTANT TO CONTINUE TO SUPPORT
FUNDING PROGRAMS LIKE CCHI.
IF THIS RENEW CONCEPT IS
APPROVED, WE WANT TO CONTINUE TO
FOCUS ON DEFINING MOLECULAR
MECHANISMS OF HUMAN HUMAN IMMUE
REGULATION AND SUPPORT
CENTRALIZED THE INFRASTRUCTURE
TO PROMOTE AND COORDINATE
MULTI-DISCIPLINARY RESEARCH.
WHICH HAS BEEN PROVED TO BE
SUCCESSFUL IN REDIRECTING
RESEARCH FOCUS UNDER URGENT
PUBLIC-HEALTH SITUATIONS.
WE WANT TO SUPPORT DEVELOPMENT
OF INNOVATIVE TECHNOLOGIES TO
FACILITATE IMMUNE STUDIES IN
HUMANS.
SO WE WANT TONE COURAGE ANALYZE
THE CONSEQUENCES OF INFECTION
AND VACCINATION IN POPULATION
WITH CO-MORBIDITY AND TO LOOK AT
THE IMPACTS OF PRO EXISTING
IMMUNITY ON SUBSEQUENT INFECTION
OR VACCINATION AND A STUDY
FOCUSING ON MECHANISMS OF IMMUNE
DISEASES.
IDENTICAL TO THE CURRENT
ITERATION, WE WERE ALLOWED SMALL
MECHANISTIC CLINICAL TRIALS AND
PERMIT ANIMAL STUDIES THAT
EXTEND OR GUIDE MECHANISTIC
ANALYSIS OF HUMAN SAMPLES AND SO
CO-OPERATIVE AND MECHANISMS AND
SO, I'LL STOP HERE AND I'M HAPPY
TO TAKE ANY QUESTIONS.
LET ME JUST REMIND COUNCIL
MEMBERS OR MEMBERS OF THE PUBLIC
WHO ARE IN THE CALL TO RAISE
YOUR HAND OR GO ON VIDEO AND
WHEN YOU SPEAK GO ON VIDEO.
>> I HAVE A QUESTION, I SEE
UNDER SCOPE, THIS IMPACT OF THE
EXISTING AND INFECTION AND
VACCINATION AND THIS COMES TO
MIND THE ASSOCIATION OF THESE
STUDIES WITH MACHINE LEARNING
AND ARTIFICIAL INTELLIGENCE AND
INCORPORATE AND THIS WITH ALSO
MORE COMPUTATIONAL EFFORTS AND
TO HARNESS ON VAST AMOUNTS OF
PREDICTIONS AND THINGS THAT OF
NATURE.
>> THAT'S A GOOD SUGGESTION AND
THE CCHI GROUP AT THIS TYPE OF
EFFORT IS ON GOING RIGHT NOW AND
HOWEVER, I THINK WE NEED
ENCOURAGE MORE LIKE STUDIES AND
THERE ARE COVID REALLY BROWN UP
THE OPPORTUNITY OF USING MACHINE
LEARNING PROGRAMS TO PREDICT
OUTCOMES, ON THE OTHER HAND, I
THINK THAT'S WHAT BCHI IS
PERFECTLY FOR IS TO SUBSEQUENT
TO DO THE MECHANISTIC STUDY TO
VALIDATE THAT PREDICTION IN
EITHER THE HUMAN COHORT OR
PRIMARY HUMAN CELLS OR EVEN
ANIMAL MODEL.
>> THANK YOU.
>> SO IF THERE ARE NO OTHER
COMMENTS OR QUESTIONS.
IN THE INTEREST OF TIME, WE'LL
ASK YOU FOR AN ON BLOCK
RECOMMENDATION AT THE END OF THE
FOUR PRESENTATIONS.
AND IN THAT CASE WE CAN MOVE ON
TO MERCY, YOU ARE GOING TO
PRESENT THE IMMUNITY IN OLDER
ADULTS CONCEPT CLEARANCE.
>> GOOD AFTERNOON, I'LL BE
PRESENTING THIS CONCEPT ON
IMMUNITY IN OLDER ADULTS FO FY2.
SO AS WE KNOW, RELATED TO AGE
DECLINES IN IMMUNE FUNCTION AND
THEY ARE ARE A VARIETY OF
DECLINES THAT ARE SEEN LOOKING
AT INNATE SYSTEMS AS WELL AS
VACCINE EFFICIENCY AND DIVERSITY
AND IT'S LOW GRADE CHRONIC
INFLAMMATION THAT CONTINUES IN
OLDER AGE AND SO THE -- JUST TO
GIVE YOU A QUICK BACKGROUND OF
THIS PROGRAM, IT BEGAN IN 2009
AND THE -- WITH REJUVENATION IN
ANIMAL MODELS FOCUSING ON THE
THYMIC AND THE STUDIES AND THEN
IN THE SUBSEQUENT ITERATION OF
THIS PROGRAM, IT WAS THEN WHERE
WE INCLUDE HUMAN STUDIES, IT WAS
SPECIFICALLY FOR THE ELDERLY
WHERE WE HAD HUMAN STUDIES AS
WELL AS ANIMAL STUDIES AND THEN,
IN ALL THE AND WE HAVE A VARIETY
OF CO-SPONSORS AND CURRENTLY
ONLY NIA AND NIAID ARE THE ONES
THAT IN THE PROGRAM AND THE ONE
SUNSHINE AND AVAILABLE FOR
ANYTHING.
SO SOME OF THE KEY
ACCOMPLISHMENTS ASSOCIATED WITH
THIS PROGRAM, AGE ASSOCIATED
WITH AGE AND INDEPENDENT AND AND
PHENOTYPE BY A SMALL PREPORTION
OF -- THAT COULD INCLUDE UP
REGULATION OF MARKERS OR
INCREASED REACTIVE ISSUES AND
THEN INTEGRATION OF VARIOUS
CHANGES THAT UNDER LIE HEALTHY
VERSUS DYSFUNCTIONAL OR
DIS-REGULATED CONDITIONS THAT
WOULD ALSO HELP TO CREATE USEFUL
IMMUNE HEALTH GRADE.
THIS COULD INCLUDE ACCELERATED
OR PREMATURE PHENOTYPES WITH
CHRONOLOGICAL VERSUS BIOLOGICAL
AGE AND CURRENTLY THE
INVESTIGATORS IN THE PROGRAM
HAVE ACCOMPLISHED ALMOST 50
RESEARCH PUBLICATIONS.
AND I'D LIKE TO JUST GIVE A FEW
EXAMPLES OF FINDINGS FROM THE
PROGRAM.
AND THE FIRST ONE IS WHERE
AUTOIMMUNE C TELLS AND THE SO IN
THIS CASE, A STUDY FROM THE LAB
REPORTED A DEFECT IN THE DNA
REPAIR MECHANISM IN T CELLS THAT
BANKRUPTED IN REPAIR AND ON THE
MRE11A AND THOSE EFFECTIVE IN T
CELLS IN PATIENTS WITH RA AND
THE ARTHRITIS AND THEY SHOWED
THAT THE LOSS OF FUNCTION OF
THIS NEW NUCLEUS RESULTED IN
MITOCHONDRIAL FAILURE AND TISSUE
MTDNA AND PROMOTING TISSUE
INFORMATION.
AND ANOTHER GROUP, IDENTIFIED
AND CELL EYE EXPRESS IT SHOWED
THE FACTORS THAT DEFINE THIS
POPULATION AND THEN OLDER AND
YOUNGER ADULTS AND SO WE FIND
THAT THE YOUNG ADULT HAD THE
POPULATION OF MEMORY T CELLS
WHICH WERE CHARACTERIZED BY
SEVERAL TRANSCRIPTION FACTORS
TWO AND THROW AND EOMES FOR
EXAMPLE AND WE HAVE THE OLDER
POPULATION THEY FOUND THAT THE
MEMORY T-CELL POPULATION HAD NO
AMOUNTS OF, THEY ACTUALLY SAW
THE DECREASE IN THE POPULATION
OF THE CD PRODUCT CELLS AND THEN
FROM THE GROUPS, THEY FOUND THAT
THESE CD8 CELLS TO BE MORE MK
LIKE AND AND THE RENEWAL OF THE
PROGRAM IN 24, THE PROPOSED
SUPPORTING STUDIES WHICH DEFINE
MECHANISMS THAT CONTRIBUTE IN
THE DYSFUNCTION AND LOOK AT VERY
STRATEGIES INCLUDING IMPROVING
HOSTING IMMUNE FUNCTION AND
INFECTIONS IN OLDER ADULTS AND
WE ALSO WANT TO ENCOURAGE FOLKS
TO USE SAMPLES FROM HUMAN
COHORTS THAT ARE ESTABLISHED OR
FROM CURRENTLY INDEPENDENTLY
CLIN TAL TRIALS OR THEY COULD
ALSO ESTABLISH NEW COHORTS TO
STUDY THE HUMAN FUNCTION AND FOR
THE FUTURE EMPHASIS AND ALSO
ENCLOUD LOCKING AT MECHANISMS
AND IMPACT OF VARIOUS ANALYTICS
WHICH ARE DRUGS THAT DESTROY AND
LOCK AT EPI GENETIC CHANGES AND
VACCINE AND RESPONSES TO
MECHANISMS OF AGING AND THEN IN
THE PAST FEW YEARS, THERE'S ALSO
BEEN VARIOUS TOOLS DEVELOPED TO
MONITOR IMMUNE HEALTH AND
LOOKING AT AGE OR AIAS WHICH
HAVE DIFFERENT TOOLS THAT FOLKS
HAVE COME UP WITH BASED ON THIS
STUDY LOOKING AT THE AND
EXPRESSION OR OTHER IMMUNO
METRICS OR ALSO LOOKING AT AND
WHETHER IT'S AGING RELATED AND
AGING INDEPENDENT AND SO WE AND
CONTINUE OUR PARTNERSHIP WITH
THE AGING INSTITUTE AND WE'D
LIKE TO HAVE THIS MECHANISM BE
THE MECHANIC IN THE NEXT
ITERATION AND SO IF YOU HAVE ANY
QUESTIONS WE'LL BE TO THANK YOU,
VERY MUCH.
>> I'M SORRY, I AM NOT ABLE TO
TURN ON MY VIDEO.
IT WOULD INCLUDE CLINICAL.
>> YES, IT WOULD.
>> OK.
>> YOU ARE PLANNING TO BRING THE
GROUPS TOGETHER PERIODICALLY WE
WILL BRING THE GROUPS TOGETHER
AND WE'LL HAVE ENCOURAGE
COLLABORATION AND ACROSS VARIOUS
CENTERS OR GROUPS BASICALLY,
THAT'S WHAT WE'D LIKE TO DO.
CONRAD, LET'S MOVE ON.
MAINTAINING DAY AFTER
VACCINATION AND INFECTION.
>> I HAD A LITTLE TROUBLE WITH
THE SHARING.
I DON'T KNOW WHY, SO ERIC IS
GOING TO BRING IT UP.
THANK YOU, ERIC.
AND I'M JUST GOING TO ADVANCE
THE SLIDES VERBALLY WITH HIM.
THIS IS INITIATIVE IS
MAINTAINING IMMUNITY AFTER
IMMUNIZATION.
IT WAS INITIATED IN 2019 AND
THIS IS A RENEWAL OF THAT
INITIATIVE.
NEXT SLIDE, PLEASE.
SO THE BACKGROUND.
THE DURABILITY OF VACCINES
PROTECTION VARIES AS WE VARY
WELL KNOW NOW.
AND SMALLPOX VACCINES CAN
PRODUCE LIFETIME OF IMMUNITY AND
THE SARS-CoV-2 VACCINE AND
SOME PERTUSSIS VACCINES CAN ONLY
PROTECT FOR A FEW YEARS AND
MONTHS AND WE WANT TO DEFINE WHY
THAT IS AND SO A BETTER
UNDERSTANDING OF THE IMMUNE
MECHANISMS AND THE COMPONENTS
THAT LEAD TO THE SUSTAINED
IMMUNITY CAN HELP TO DESIGN IN
VACCINES.DOU DESIGN OF FUTURE
THIS IS MENTIONED BEFORE, THAT S
SUPPORTING GRANTS AND WE
CURRENTLY HAVE SEVEN THEM.
AND NEXT SLIDE.
SO FAR SINCE 2019 WE'VE HAD 54
PUBLICATION AND A LOT OF THEM IN
HIGH I AM IMPACT JOURNALS AND I
THOUGHT I WOULD MENTION A FEW
HIGHLIGHTS OF THE THINGS THAT
WE'VE DONE AND THAT ISOLATION
AND CHARACTERIZATION OF
INFLUENZA ANTIBODIES AND IT
SEEMS TO PROTECT AGAINST
INFLUENZA INFECTION AND MOUSE
MODELS AND.
>> WE KNOW MORE ABOUT THIS THIS
WAS A LITTLE WHILE AGO AND IT'S
IMPORTANT TO CHARACTERIZE BUT
THIS IMMUNE RESPONSE IS.
AND WHICH IS TALKING ABOUT
VACCINATION AND AND IT SEEMS TO
CONCERN COMPONENTS OF THE T-CELL
RESPONSE AND EVEN A LITTLE BIT
OF THE HUMORAL IMMUNE TONS AND
JUST ANOTHER FINDING IS
PROTECTIVE IMMUNITY REQUIRES
BOTH NAIVE AND MEMORY B CELLS
AND INFLUENZA BACK SCENES
INDUCED LIP SNOWED CENTERS
STRUCTURES AND THIS INVOLVES
CROSS HYBRID IMMUNITY AND NOT
HYBRID IMMUNITY AND BECAUSE THIS
IS SOMETHING THAT IS A NEW
ANTIGEN I JUST WANTED TO SHOW
YOU WHAT THESE JOURNALS, THESE
WERE IN AND THESE FINDINGS AND
NEXT SLIDE.
SO, THE RENEWAL.
IS THE OBJECTIVES ARE TO DEFINE
THE IMMUNE COMPONENTS THAT ARE
STIMULATED AFTER VACCINATION IT
WAS THE ORIGINAL AND WE'RE STILL
PURSUING THAT AND DETERMINE HOW
THESE RELATE TOWN DUCK AND
MAINTENANCE OF PERSISTENT IMMUNE
RESPONSES.
AND MAKE THAT CONNECTION TO BE
FOCUSED ON THAT CONNECT AND THEN
WE'RE TRYING TO HOPE TO GET
PROJECTS WHICH WOULD DEFINE
DIFFERENCES BETWEEN HUMOR ALL
AND CELLULAR IMMUNE RESPONSE AND
WORE GOING TO ASK FOR THAT AND
COMPARED TO INFECTION AND THE
RESPONSE AFTER INFECTION
COMPARED TO VACCINATION.
AND TO SEE HOW THAT EFFECTS THE
DURABILITY OF IMMUNITY.
AND TO REEMPHASIZE IMPORTANT
EMERGING AREAS THAT WE HAVE NOT
DISCOVERED AS MUCH IN OUR
CURRENT PROGRAMS FOR EXAMPLE,
TISSUE RESIDENT MEMORY, VERY
IMPORTANT, RIGHT, AND THE IMMUNO
MA TAB LOAM AND THE FUNDING
MECHANISM IS GOING TO BE UO1
CO-OPERATIVE AGREEMENT AND RO1
SIZE GRANTS AND WE ANTICIPATE
ABOUT MAKING ABOUT FIVE TO EIGHT
AWARDS.
AND I THINK THAT'S THE LAST
SLIDE.
I'LL TAKE ANY QUESTIONS THAT YOU
HAVE NOW.
SORRY FOR THE BACKGROUND LAWN
MOW ARE NOISE.
I DON'T KNOW IF YOU HEAR THAT.
IT HAPPENED ALL OF A SUDDEN.
>> WELL IT'S ALL QIU ET O QUIE.
WE'LL MOVE ON TO CENTERS OF
EXCELLENCE, DAVID, YOU ARE UP.
>> THANK YOU.
THIS SHOULD BE SHOWING.
>> IT IS AND WE CAN HEAR YOU
THIS TIME.
THANK YOU.
OK, SO GOOD AFTERNOON, I WILL
PRESENT THE RENEWAL OF THE
AUTOIMMUNITY CENTERS OF
EXCELLENCE ABBREVIATED ACE.
THE PROGRAM PURPOSE IS TO
EXCELERATE TRANSITION OF LAB TO
THE CLINIC OF NEW THERAPIES
AUTOIMMUNE DISEASES AND IMPROVE
THE FUNDAMENTAL UNDERSTANDING OF
OUR CURRENT THERAPIES AND THE
APPROACH IS TO FOSTER
COLLABORATIONS BETWEEN BASIC AND
CLINICAL SCIENTIST AND IF SIL
CO-OPERATIVE CLINICAL TRIALS IN
AUTOIMMUNE DISEASES.
THIS SHOWS THE HISTORY OF THE
ACE IT WAS INITIATED IN 1999
WITH FOUR CENTERS AND EXPANDED
IN 2004 AND RENEWED AGAIN IN
2014 AND BROKEN INTO TWO
MECHANISMS, UM1 FOR THE CLINICAL
AND BASIC U19.
19 RENEWED IN 2019
WITH EXTREME CLINICAL PROJECTS.
ANIMAL MODELS ARE NOT PERMITTED
AND THE CURRENT CYCLE HAS 10
CENTERS.
FIVE CLINICAL AND FIVE BASIC AND
THOSE ARE COORDINATED
COMPOSEDDED OF PI AND
REPRESENTATIVE OF THE STATISTICS
AND CLINICAL CENTER AND THERE
ARE TWO ANNUAL STEERING
COMMITTEE MEETINGS, ONE
INCLUDING ALL INVESTIGATORS AND
A SINGLE FUNDS MANAGEMENT CORE
AT ONE CENTER SUPPORTS THE
NETWORK ACTIVITIES INCLUDING
CLINICAL PROJECTS NOW CLINICAL
PROJECTS IS A CLINICAL TRIAL AND
TOGETHER WITH A MECHANIC NICE
TICK STUDIES AND ALSO
COLLABORATIVE PROJECTS MORE ON
THE ACES RESPOND TO THE PANDEMIC
AS FOUNDING MEMBERS OF PRISM
WHICH IS A TOGETHER
TRANSPORTATION BRANCH
INVESTIGATORS STUDYING COVID IN
CHILDREN.
LEADING SUBJECT ON THOSE AND
CENTERS COMPETED SUCCESSFULLY
FOR ADMINISTRATIVE SUPPLEMENTS
OF COVID AND AS I MENTIONED THE
COLLABORATIVE PROJECT.
THIS IS A SECOND PROGRAM CYCLE
WHICH APPLICANTS DESCRIBED THEIR
PLANS FOR COLLABORATIVE PROJECTS
AND HOW THEY WOULD CONTRIBUTE
AND HOW THEY WOULD BENEFIT FROM
THE GROUP.
AND THESE PROJECTS WERE
COORDINATED SUCCESSFULLY POST
AWARD WITH ALL CENTERS
PARTICIPATING IN THESE THREE
COLLABORATIVE PROJECTS
ONE INBIOMARKERS AND THE THIRD
ON IMMUNE RESPONSES AND
PERIPHERAL TISSUES.
THEY INCLUDE THESE FOUR
ENROLLING AND TO THE FIRST IS
BLOCKING SLAM F7 AND IGG4
RELATED DISEASES AND THE SECOND
USES A ANTIBODY IN EARLY
RELAXING MULTIPLE SCLEROSIS AND
THE THIRD IS KINASE AND PHOTO
SENSITIVITY AND LIEU US AND THE
FOURTH IS A STUDY IN SYSTEMIC
LUPUS AND THE FIFTH IN
DEVELOPMENT IS TO TREAT JUVENILE
IDIOPATHIC ARTHRITIS.
SO IN TERMS OF CHALLENGES FROM
THAT AND ACCOMPLISHMENTS
INCLUDE, AGAIN, THE DEVELOPMENT
OF THE FOUR CLINICAL PROJECTS
AND ONE IN DEVELOPMENT AND ONE
OF FOUR AREN ROLLING AND ONE IN
DEVELOPING AND SUPPORTING ON
GOING LEGACY CLINICAL TRIALS AND
I WON'T GO INTO THOSE.
WE HAVE ESTABLISHED AN
INEFFICIENT FUNDS MANAGEMENT
CORE AGAIN AND FOSTER
COLLABORATIONS, THIS IS A
FORMULATED COLBORATIVE
RESEARCH AGENDA AND THIS IS A
FIVE-YEAR PLAN POSTED WITH THE
ENTIRE PROGRAM, POSTED ON THE
PUBLIC ACE WEBSITE AND UPDATED
ANNUALLY WITH PROGRESS REPORTS
AGAIN PUBLICLY.
AND AS I SHOWED YOU, THEY
INITIATED THREE COLLABORATIVE
PROJECTS INCLUDING ALL CENTERS.
THEY HAVE MAINTAINED HIGH
SCIENTIFIC PRODUCTIVITY AND
THERE HAVE BEEN 162 ORIGINAL
PAPERS AND REVIEW ARTICLES MANY
IN HIGH-IMPACT JOURNALS AND THAT
IS THROUGH APR OF 202020.
AND 35 PUBLICATIONS OF COVID-19.
IN ELSE TESTIFY CHARGES EMERGING
INCLUDING THE PANDEMIC, THESE
RESPONDED TO THE PANDEMIC BY
JOINING WITH COLLABORATE FROM
THE TRANSPLANTATION COMMITTEE TO
FORM PRISM ON SARS-CoV-2
STUDYING THE MULTI SYSTEM
INFLAMMATORY INDROP IN CHILDREN
OR MIS-C.
THIS PROGRAM IS PERFORMING
IN-DEPTH IMMUNE ANALYSIS IN MORE
THAN 240 CHILDREN WITH COVID.
THE ACE ALSO DEVELOPED A TRIAL
AND STUDY OF COVID VACCINES AND
IN AUTOIMMUNE SUBJECTS THAT
SHOWN ACBO-1 RIGHT THERE AND
IT'S RANDOMIZED ADAPTIVE TRIAL
THAT IS COMPLICATED ACTUALLY.
I'M NOT DIRECTLY INVOLVED WITH
THAT.
ACVO2 IS A SMALLER STUDY AND
MORE LIKE A MECHANIC NICE TICK
TRIAL PART OF THE PROJECTS.
AND AGAIN, COUPLE OF THE CENTERS
HAD SUCCESSFULLY COMPETED FOR
ADMIN SUPPLEMENTS IN COVID.
IN TERMS OF CHALLENGES
REMAINING, OUR PLANS FORT
RENEWAL, WE HOPED TO FURTHER
STRENGTHEN ANALYSIS OF CLINICAL
TRIALS BY FORMING A DEDICATED
MESSNESS TICK STUDY TEAM THAT
WOULD HELP KEEP CURRENT THE USE
OF SAMPLES LEVERAGING THE NET
EXPERTISE AND PROMOTE SECONDARY
ANALYSIS OF CLINICAL TRIALS
SAMPLES AND WE THINK WE CAN
ASSIST IN THAT AND FOSTER THAT
BY HAVING A COORDINATED
COLLECTION AND PROVISION OF
CLINICAL TRIALS SAMPLES THROUGH
A ACE REPOSITORY CORE THAT WOULD
BE INSTRUCT ACTUALLY NEW AND
DEVELOP SAMPLE SET COLLECTION
AND ANALYSIS.
NOW, THE RENEWAL STRUCTURALLY
LOOKED LIKE THIS TWO SEPARATE
MECHANISMS A UM1 AND UM19.
UM1 NEITHER OF THE TWO ACTUALLY
ON THEIR OWN CHANGED MUCH BUT
ALL THE APPLICANTS ARE OBLIGED
TO PROPOSE A CO COLLABORATIVE AD
ADMINISTRATIVE CORE NOT NEW AND
AND ACE AND THAT WOULD BE NEW
AND MANAGEMENT ONE NETWORK A
HARD AND THEY WOULD BE OBLIGED
TO APPLY.
I HOPE YOU'VE HEARD ME AND I'M
HAPPY TO TAKE ANY QUESTIONS.
>> THANK YOU, IT LOOKS GOOD.
>> SORRY.
MY VIDEO IS LIKE TURNED OFF SO I
CAN'T TURN IT ON.
>> THAT'S OK.
I UNDERSTAND.
SO, I DON'T SEE ANY OTHER
QUESTIONS OR HANDS UP SO, AT
THIS POINT WE'RE A BIT AHEAD OF
SCHEDULE WHICH IS FINE AND WE
CAN ASK FOR AN RECOMMENDATION
AND MOTION AND A SECOND FOR ALL
OF THE CONCEPT CLEARANCES.
>> SO MOVED.
>> SECOND.
>> OK.
DOES THAT TAKE CARE OF ALL OF
THE OFFICIAL BUSINESS.
>> THE COUNCIL MEMBERS WILL NEED
TO GO INTO THE ECD AND APPROVE
THE RESEARCH CONCEPT CLEARANCE
AND THAT WILL DO IT.
>> TERRIFIC.
OK.
WELL, IN THAT CASE, WE CAN
WRAP-UP AS SOON AS YOU ALL DO
THAT AND LOOK FORWARD TO, I
HOPE, SEEING YOU IN-PERSON
FAIRLY SOON.
AND --
>> WILL THE FALL MEETING BE
IN-PERSON?
>> WE DON'T KNOW YET.
I THINK IT'S -- HOPEFULLY WE
WILL BE BEYOND COVID TRAVEL
RESTRICTIONS AND MEETING
RESTRICTIONS THEN AND WE'LL SEE.
I THINK THE EXPERIENCE WITH
COVID AND DOING THESE REMOTELY
BY WEB, HAS BEEN GOOD ENOUGH OUR
EXPECTATION IS THAT FOR THE
WINTER MEETING AND JANUARY IN
TRAVEL IS AN ISSUE WE WILL DO
THOSE REMOTE LEROUX TEENLY GOING
FORWARD AND WE'LL SEE ABOUT THE
FALL AND MAY AND JUNE COUNCIL AS
THIS UNFOLDS.
>> OK.
>> THANK YOU.
>> IF ANY OF YOU HAVE THOUGHTS
OR SUGGESTIONS ABOUT HOW WELL
THIS IS WORKING AND WHETHER IT'S
A GOOD IDEA TO MEET IN-PERSON
MORE FREQUENTLY AND THEN ONCE A
YEAR OR THE TIMES SAY OF TERM
TRAVEL IS VALUABLE TO YOU, WE'RE
HAPPY TO HEAR YOUR COMMENTS
EITHER RIGHT NOW OR PRIVATELY BY
E-MAIL.
>> WE DID GET ACTUALLY A SURVEY
TO RESPOND TO SO, WE DID.
>> I MISSED THE SURVEY BUT I
SAID ONCE A YEAR MAY B BALANCE E
PROS AND CONS.
THE TIME SAVED IN TRAVEL IS
WELCOME BUT IT'S REALLY NICE TO
BE ABLE TO INTERNET ARE ACT.
THE DIFFERENT GROUPS ACROSS WE
WOULD SEE EACH OTHER IN THE
HOTEL OR AT LUNCH AND THOSE WERE
VALUABLE EXPERIENCES.
I THINK MEANINGFUL ALL AROUND IN
ADDITION TO INTERACTING WITH YOU
GUYS AT NIH.
>> YEAH, I AGREE.
GWEN, I TOOK IT YOU WERE SAYING
MEET IN-PERSON ONCE AND THAT
MIGHT BE FREQUENT ENOUGH OR WERE
YOU SAYING?
>> THAT MIGHT BE FREQUENT
ENOUGH.
THERE ARE PROS AND CONS TO EACH
APPROACH.
I'M NOT SURE ROBIN THINKS ABOUT
IT BUT ONCE OR TWICE A YEAR
WOULD BE NICE.
>> I TOTAL TOTE AGREE.
I HAVE THE SAME OPINION.
>> GOOD.
>> ALL RIGHT.
>> BIG QUESTION IS WILL IT BE
THE WINTER THAT IS THE WORSE
TIME TO TRAVEL, RIGHT, BECAUSE I
WAS SUPPOSED TO GO TO AAI THAT'S
WHAT I GOT COVID IN MAY I WOULD
HAVE BET MAY WOULD HAVE BEEN THE
SAFEST MONTH OF THE YEAR.
IT'S REALLY HARD TO TELL.
>> SAME THING HAPPENED AT ETS
SEVERAL PEOPLE CAME DOWN AND I'M
OFF TO ASPEN FOR A WEEK AND THE
HONG KONG AND THE VIRUS IS
CHANGING FASTER THAN THE
VACCINES AND THE VIRUS WILL TELL
US WHEN IT'S DONE WITH US.
>> YEAH, EXACTLY.
>> I WANTED TO ASK THE QUESTION
BUT I DON'T KNOW THAT WE KNOW
THE ANSWER BUT ON ONE HAND WE
HEARD THAT CORONAVIRUS IMMUNITY
JUST TENDS TO BE SHORT AND THAT
IS HISTORICALLY TRUE, RIGHT,
EVEN BEFORE SARS-CoV-2 BUT THE
NASAL VACCINE IS GETTING A LOT
OF DISCUSSION, WILL IT BE
BETTER?
I DON'T THINK WE KNOW THE ANSWER
TO THAT.
>> NOT AT ALL.
>> WELL HOPEFULLY FOR ONE NASAL
VACCINE SOMETIMES FAIRLY SOON
AND ABOUT SHORT TERM IMMUNITY
BUT IT'S GOING TO TAKE A LONG
TIME AND WILL REQUIRE THE VIRUS
CONTINUES TO TRANSMIT AND BE
CIRCULATING WIDELY TO KNOW
WHETHER THERE'S EVEN A REAL
PROTECTION.
>> YES.
>> THE HOSPITALIZATIONS DID NOT
RISE AND THERE'S A HUGE RISE
LOCALLY INFECTION AND IN FACT,
IT ALSO JUST EVEN UNIVERSITY
ALMOST EVERYONE I KNOW GOT COVID
THIS MAY AND REALLY
HOSPITALIZATIONS DIDN'T RISE AND
I THINK THAT'S A GOOD SIGN.
>> IT'S PREVENTING SEVERE
DISEASES.
>> YEAH, BUT IT'S TRUE.
WE'RE HEARING OF A LOT OF PEOPLE
WHO HAVE MILD STAY AT HOME
DISEASE BUT SYMPTOMS TWO TO FOUR
WEEKS BEFORE THEY'RE BACK TO
THEIR NORMAL EXERCISE LEVEL AND
THE LIKE SO THAT IS A HIGH PRICE
TO PAY.
>> YEAH.
>> ABSOLUTELY.
>> ALL RIGHT.
WELL, THANK YOU ALL AND I THINK
WE'LL JUST WRAP-UP HERE.
LOOK FORWARD TO HOPEFULLY SEEING
YOU IN THE FALL.
>> THANK YOU.
>> THANK YOU, EVERYBODY.