>> WELCOME TO OUR ANNUAL
KUAN-TEH JEANG MEMORIAL
LECTURE. YOU MAY HAVE NOTICED
THAT IT IS NO LONGER
ASIAN-AMERICAN, NATIVE
HAWAIIAN, PACIFIC ISLANDER
MONTH. BUT, IT'S SORT OF A
RUNNING JOKE THERE ARE SO MANY
ACCOMPLISHMENTS BY THE AANPI
COMMUNITY WE CANNOT FIT THEM
ALL IN ONE MONTH SO WE HAVE HAD
THE KUAN-TEH JEANG MEMORIAL
LECTURE IN THE FIRST WEEK OF
JUNE.
I WOULD LIKE TO START OFF WITH
SOME REMEMBRANCES OF KUAN-TEH
JEANG IN WHOSE HONOR WE ARE
HAVING THIS TALK.
NEXT SLIDE PLEASE.
TEH WAS BORN IN 1958 IN
TAICHUNG, TAIWAN AND SPEND HIS
CHILD AND LYBIA. CAME TO THE
UNITED STATES IN 1970. HE WAS A
TRUE CITIZEN OF THE WORLD, HE
EARNED HIS MD AND PHD AT JOHNS
HOPKINS AND WENT TO STUDY WITH
JOHN HAYWARD.
CAME TO NIH IN 1985 SAME YEAR I
DID AND DID POSTDOCTORAL
FELLOWSHIP WITH THE LATE DR.
GEORGE CORY. AND THAT IS
ANOTHER CONNECTION WE HAVE.
GEORGE CORY IS ACTUALLY THE
REASON I ENDED UP AT NIH. HE
GAVE A WONDERFUL TALK AT
HOPKINS WHEN I WAS THERE AND HE
SAID NIH IS THE MOST WONDERFUL
PLACE TO BE. IT RESEARCHES ONE
OF YOUR TOP PRIORITIES, THERE
IS NO BETTER PLACE THAN THE NIH
INTRAMURAL RESEARCH PROGRAM.
SO AFTER HIS POSTDOCTORAL
FELLOWSHIP, HE MOVED TO THE
NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES AND
BECAME KEYS OF THE MOLECULAR
VIROLOGY SECTION, IN THE
LABORATORY OF MOLECULAR
MICROBIOLOGY, WHERE HE STUDIED
THE HUMAN IMMUNODEFICIENCY
VIRUS AND THE RELATED BUYERS
HTLV-1.
HE WAS THE EDITOR-IN-CHIEF OF
RETROVIROLOGY. AND LATER IN THE
NIH VIROLOGY INTEREST GROUP AND
A LEADER IN THE CHINESE SOCIETY
OF BY SCIENTISTS IN AMERICA IN
A BIG ADVOCATE FOR RACIAL
MINORITY GROUPS AND PERSONS
WITH DISABILITIES.
AND WE CONTINUE TO CHERISH HIS
MEMORY AND LEGACY. THIS IS A
PICTURE OF HIS FAMILY. HIS
FAMILY COULD NOT BE HERE TODAY
BECAUSE THERE ACTUALLY IN
TEXAS, CELEBRATING THE END OF
THE RESIDENCY OF ONE OF HIS
DAUGHTERS.
AND, IF YOU GET A CHANCE, WE
ACTUALLY HAVE A MEMORIAL GARDEN
IN BETWEEN BUILDING 31 AND
BUILDING 33. AND YOU CAN SEE
THAT AT YOUR LEISURE.
I WOULD LIKE TO TURN OVER THE
PODIUM TO DAVID RICE, FROM OUR
OFFICE OF EQUITY, DIVERSITY AND
INCLUSION WHO WOULD LIKE TO SAY
A FEW WORDS ABOUT THE OCCASION.
>> [APPLAUSE]
>> THANK YOU DR. OWENS. IT IS
MY PLEASURE TO BE HERE. WHILE
VIEWING YOUR SLIDES EARLIER
TODAY I FELT THAT YOU AND DR.
PAN-YUN TING, 1985. THAT IS
WHEN I WAS BORN. AND IT IS
GREAT THAT THE WORK AT NIH HAS
BEEN GOING ON FOR A LONG TIME,
AND MANY YEARS TO COME; THANK
YOU AGAIN FOR ALLOWING US TO BE
HERE AND INVALUABLE PARTNERS OF
THE OFFICE OF INTRAMURAL
RESEARCH, YOUR SUPPORT AND
COLLABORATION IN THE OFFICE OF
DIVERSITY, EQUITY AND INCLUSION
ARE DEEPLY APPRECIATED.
AS WE MOVED TO THE
ASIAN-AMERICAN, PACIFIC
HAWAIIAN AND NATIVE AMERICAN
MONTH WE FOCUS ON TWO KEY
POINTS IN VERSE WE CELEBRATE ON
KUAN-TEH JEANG -- I NEVER HAD A
CHANCE TO MEET HIM. BUT MANY OF
THE ROOM HAVE AN ONLINE TODAY,
ONE OF THE LEADING SCIENTISTS
IN BIOLOGY.
HE DEDICATED HIS LIFE TO
SCIENCE. BUT HE WAS ALSO A
FIERCE ADVOCATE FOR
REPRESENTATION OF ASIAN
AMERICAN, AND LEADERSHIP
POSITIONS. AT THE OFFICE OF
EQUITY, DIVERSITY AND INCLUSION
WE ARE COMMITTED TO CONTINUING
THIS LEGACY BY DEVELOPING
STRATEGIES WORKING WITH OUR
PARTNERS IN THE NIH AND THE
BIOMEDICAL RESEARCH ENTERPRISE
AND CREATE PATHWAYS FOR FUTURE
GENERATIONS FOR ASIAN AMERICANS
TO ACHIEVE HIS VISION FOR MORE
ASIAN AMERICANS IN SCIENTIFIC
LEADERSHIP POSITIONS SOME OF
YOU MAY OR MAY NOT KNOW I CAN
SEPTEMBER 2022 OUR OFFICE IN
BARNSTABLE THE NATIONAL CANCER
INSTITUTE AND THE NATIONAL
INSTITUTE OF MENTAL HEALTH, AND
THE NATIONAL INSTITUTES OF
MINORITY HEALTH AND HEALTH
DISPARITIES PUBLISHED AN
ARTICLE ON THE FRONTIER JOURNAL
EXAMINING THE ASIAN-AMERICAN
LEADERSHIP GAP. IF YOU HAVE NOT
SEEN IT, GO AHEAD AND REVIEW
THE ARTICLE.
ONE OF THE KEY RECOMMENDATIONS
FROM THE ARTICLE, WHICH WAS TO
IMPROVE WORKPLACE CULTURE TO
REFLECT ASIAN-AMERICAN
WORKPLACE EXPERIENCE
ACCURATELY, THIS RECOMMENDATION
LEADS TO MY SECOND WEEK OF
REFLECTION THIS YEAR THE
ASIAN-AMERICAN NATIVE AMERICAN,
HAWAIIAN PACIFIC ISLANDER'S
THEME WAS EMBRACING BELONGING,
HONORING LONG-STANDING
TRADITION WHILE EMBRACING NEW
ONES.
AS YOU HAVE SEEN IN THE MONTH
OF MAY, THERE WERE NUMEROUS
EVENTS ACROSS NIH FOR INSTANCE
THE INSIDE LECTURE BY DR.
MURPHY WHERE WE EXPLORE THE
CRUCIAL IMPORTANCE OF
DEVELOPING SOCIAL CONNECTIONS
AND ADDITIONALLY JUST THIS PAST
WEEK I BELIEVE ON THURSDAY THE
BELONGING EVENT HOSTED BY THE
KOREAN WOMEN SCIENTISTS
ASSOCIATION WAS AMAZING, THE
MUSIC FOOD AND DISCUSSION
INVOLVED THERE WERE MANY OTHER
EVENTS ACROSS THE INSTITUTES
AND CENTERS, THAT CONTRIBUTED
TO THE SUCCESS OF THESE YEAR'S
ASIAN-AMERICAN MONTH, TO
IMPROVE THE CULTURE FOR
ASIAN-AMERICAN, NATIVE HAWAIIAN
PACIFIC ISLANDERS.
HOWEVER A WORKING COMMITMENT
CANNOT STOP AFTER ONE MONTH
MUST EMBRACE THE IDEA THAT
WERE CULTURE SHOULD REFLECT
EXPERIENCES OF NOT ONLY THE
ASIAN-AMERICAN, NATIVE
AMERICAN, PACIFIC ISLANDERS,
BUT ALL UNDERREPRESENTED
COMMUNITIES EVERY SINGLE DAY OF
THE YEAR, 365 DAYS AND 366 DAYS
ON THE LEAP YEAR.
IN CONCLUSION WHILE WE
CELEBRATE THE ACKNOWLEDGMENTS
OF ASIAN-AMERICAN, NATIVE
AMERICAN, PACIFIC ISLANDERS IN
THIS COMMUNITY WE IT THE OFFICE
OF DIVERSITY AND INCLUSION, WE
PLAN ON CARRYING OUT HIS LEGACY
AIMING TO ENSURE FUTURE
GENERATIONS OF ASIAN-AMERICAN,
NATIVE AMERICAN, PACIFIC
ISLANDERS HAVE INEQUITABLE
PATHWAY INTO SCIENTIFIC
LEADERSHIP.
OUR CALL TO ACTION FOR EACH OF
YOU HERE IS TO HELP NIH CARRY
OUT THIS MISSION BY ENSURING
THE WORKPLACE CULTURE FOR ALL
COMMUNITIES. AND THIS IS FOR
EVERYONE HERE, EVERYONE ONLINE
AND EVERYONE WITHIN THE
BIOMEDICAL RESEARCH ENTERPRISE.
AGAIN THANK YOU DR. OWENS FOR
ALLOWING OUR OFFICE TO
PARTICIPATE TODAY AND I WILL
HAND IT BACK OVER TO YOU TO
INTRODUCE DR. JENNY PAN-YUN
TING.
>> [APPLAUSE]
>> IT IS MY PLEASURE TO
INTRODUCE OUR 2024 KUAN-TEH
JEANG MEMORIAL LECTURE, DR.
JENNY PAN-YUN TING.
JENNY PAN-YUN TING WAS BORN IN
BANGKOK THAILAND, SHE CAME TO
THE UNITED STATES AND STUDIED
IT PHD FROM NORTHWESTERN
UNIVERSITY IN IMMUNOLOGY AND
THAT HER POSTDOCTORAL TRAINING
AT THE UNIVERSITY OF CALIFORNIA
AND DUKE UNIVERSITY JOIN THE
FACULTY OF THE UNIVERSITY OF
NORTH CAROLINA SCHOOL OF
MEDICINE IN CHAPEL HILL. SHE
CURRENTLY HOLDS APPOINTMENTS AS
THE WILLIAM RAND KEENAN PROF.
OF GENETICS, DIRECTOR OF THE
CENTER FOR TRANSLATIONAL
IMMUNOLOGY, AND CODIRECTOR OF
THE INFLAMMATORY DISEASES
INSTITUTE. DR. PAN-YUN TING'S
HAS BROUGHT INTEREST IN THE
APPLICATION OF CUTTING-EDGE
IDEAS AND TECHNOLOGIES TO THE
STUDY OF DISEASE RELEVANT
ISSUES. MAJOR DIRECTIONS
INCLUDE INNATE IMMUNITY,
DENDRITIC CELL FUNCTION, CELL
DEATH, SIGNAL TRANSDUCTION,
GENE DISCOVERY AND A PLETHORA
OF OTHER AREAS.
CLINICAL ISSUES OF INTEREST
INCLUDE MULTIPLE SCLEROSIS,
CANCER, AUTOIMMUNE DISEASES,
INFECTION AND INFLAMMATION. DR.
PAN-YUN TING HAS OVER 300
SCIENTIFIC PUBLICATIONS AND
NUMEROUS AWARDS AND
RECOGNITIONS. INCLUDING BEING
PRESIDENT OF THE AMERICAN
ASSOCIATION OF IMMUNOLOGISTS.
AN ELECTION TO THE NATIONAL
ACADEMY OF SCIENCES. HER
LECTURE FOR TODAY IS ENTITLED:
THE BROAD IMPACT OF INNATE
IMMUNE RECEPTORS IN VIRAL
INFECTION, CANCER AND
AUTOIMMUNITY.
LET'S GIVE A BIG NIH WELCOME TO
DR. JENNY TING.
>> [APPLAUSE]
>> DR. PAN-YUN TING: THANK YOU
SO MUCH DR. OWENS. IS SUCH AN
HONOR TO BE HERE TO GIVE
TODAY'S LECTURE. I'VE BEEN AT
NIH PROBABLY 40 TIMES. GOT TO
KNOW THIS IS DATED AND REALLY
LOVE THE PEOPLE WHO ARE HERE.
AND TODAY LIKE I SAID IS A
GREAT HONOR TO GIVE THE
MEMORIAL LECTURE FOR KUAN-TEH
JEANG -- WHO ALSO WAS FROM
TAIWAN, AND LIVED IN LIBYA.
OBVIOUSLY A GENIUS LEVEL
RESEARCHER. GOT HIS PHD AT THE
AGE OF 25.
HE MARRIED HIS WIFE, FELLOW
GRADUATE STUDENT. THESE ARE
HIS RESEARCH, STARTING FROM HIS
WORK ON C AND B GENE RELATIONAL
LATER COMING TO NIH. HE WAS AT
NIH FOR 27 YEARS, AND DID MAJOR
SEMINAL DISCOVERIES ABOUT THE
ROLE OF TAT AND HLIV, AND ALSO
REVELATORY DNA AND HE WAS
BLOSSOMING, MAKING A TON OF
CONTRIBUTION IN THIS AREA.
AS WAS MENTIONED BY DAVID AS
WELL, HE WAS A CHAMPION AT THE
API, AND PRESIDENT OF THE
SOCIETY OF CHINESE BY
SCIENTISTS IN AMERICA. WELL
BELOVED BY HIS TRAINEES. AND
PUBLISHED EXTENSIVELY. AND HAS
THREE CHILDREN. SO TO CELEBRATE
HIS LIFE, AND ALSO TO CELEBRATE
DIVERSITY IN GENERAL.
AND I HAVE LEARNED A LOT TODAY,
TALKING TO DR. OWENS, ABOUT THE
MISSION THAT HE AND HIS
ORGANIZATION AT NIH HAS. SO,
TO REALLY REMEMBER THIS
WONDERFUL SCIENTISTS WHO WAS SO
PRODUCTIVE AND SO GIVING OF
HIMSELF.
WHAT I WOULD LIKE TO TALK ABOUT
TODAY IS REALLY CONCENTRATING
ON THE INNATE IMMUNE RECEPTORS
AND ON MY TALK A LITTLE BIT
ABOUT OUR OTHER WORK. BUT
MAINLY FOCUS ON INNATE IMMUNE
RECEPTORS SOMETHING WE FOCUS
FOR OVER 24 YEARS.
WHEN WE LOOK AT THE INNATE
IMMUNE SYSTEM THERE ARE MANY
RECEPTORS THAT ARE ON THE CELL
SURFACE, MOST FAMOUS THE -- WE
THINK ABOUT RECEPTORS BEING ON
THE OUTSIDE FACING THE OUTSIDE
WORLD. BUT IT TURNS OUT THAT
FOR CELLS, , JUST LIKE FOR US
RIGHT NOW THERE IS GREAT DANGER
ON THE OUTSIDE. BUT INSIDE
THERE IS ALSO A LOT OF DANGER
SO THE SYSTEM WITHIN THE CELL
HAS TO REALLY DETECT ALL OF
THESE DANGER SIGNALS, AS WE ALL
KNOW AT NIH.
WHAT I WOULD LIKE TO TELL YOU
IS OUR INTEREST IN THE INNATE
IMMUNE RECEPTOR STARTED FROM
HERE WHICH IS A FAMILY OF
PROTEINS WHERE WE DID QUITE A
BIT OF WORK ON WHICH INCLUDES
-- AND I WILL TELL YOU ABOUT
DNA SENSORS, INCLUDE SOME OF
THE ONES HERE. AND I WILL TELL
YOU ABOUT THE BROAD IMPACT OF
THESE RECEPTORS I MANY DISEASES
SUCH AS IN CANCER, INFLAMMATORY
DISEASES AND INFECTIOUS
DISEASES OF COURSE.
SO OUR VENTURE INTO INNATE
IMMUNITY WAS COMPLETELY
UNEXPECTED; WE WERE INITIALLY
INTERESTED WHEN I WAS A POSTDOC
IN IMMUNE REGULATION AND THE
IMMUNE SYSTEM.
MARY CARRINGTON WHO IS HERE, I
THINK WERE A YEAR APART IN OUR
RESEARCH EXPERIENCE AND SHE WAS
SO NICE TO JOIN MY GROUP, WHICH
WAS NASCENT, NO PROMISE AT THAT
POINT. WE LOOKED AT MHC GENE
RELATION WE LOOKED AT CIITA,
RESPONSIBLE FOR TRANSCRIPTION
OF CLASS GMH GENES. A
REMARKABLE PROTEIN BECAUSE AS I
MASTER A RELATION OF RMHC,
WHERE -- WHETHER CLASS II, ETC.
THIS IS REMARKABLE VOTING WHEN
YOU DO NOT HAVE CIITA, WHAT
HAPPENS?
SO CIITA OVER HERE, AND LOSS OF
FUNCTION MUTATIONS IN CIITA,
BASED ON THE TYPE 2 BARE
LYMPHOCYTE SYNDROME, WHERE THE
PATIENT IS NOT EXPRESSED CLASS
2 -- AS A RESULT THESE PATIENTS
ARE VERY YEARLY
IMMUNODEFICIENCY.
TWO PEOPLE IN MY LOVE DECIDED
TO SEE IF THERE WERE OTHER
GENES THAT LOOK LIKE CIITA, AND
THEY USED TWO DIFFERENT DOMAINS
IF THEY USE JUST ONE WITHOUT A
FOUND ASSEMBLY AND USING THE
NUCLEOTIDE BINDING DOMAIN CAME
UPON 22 GENES WITH DIFFERENT
END TERMINI, THAT WE EARLIER
CALLED CATERPILLAR, BECAUSE WE
WANTED TO BE VERY INCLUSIVE AND
INCLUDED ALL THE DOMAINS OF
THESE PROTEINS.
HOWEVER IT IS NOW KNOWN AS
NLRS, STANDING FOR NBD LR
PROTEINS ARE NOT RECEPTORS.
AND WHAT IS REMARKABLE IN THE
FAMILY, INITIALLY FOUND IN
PLANTS CALLED DISEASE
RESISTANCE GENES, AND SOME
PLANTS HAVE HUNDREDS OF THESE
GENES AND THEY ARE MOSTLY TO
DETECT CHANGES IN THE
ENVIRONMENT, AS WELL AS
PATHOGENIC CHANGES.
IN HUMANS, THERE ARE 22 SUCH
GENES. THEY ALL HAVE WHAT IS
CALLED A NOC DOMAIN STANDING
FOR NUCLEOTIDE BINDING REGIONS
AS WELL AND THEY REPEAT HERE
AND THEY HAVE DIFFERENT END
TERMINI. THESE ARE THE 22 NLR
PROTEINS AND SOME HAVE MANY OF
THESE PROTEIN SUCH AS THE NRP,
THERE ARE AT LEAST 11-14 SUCH
PROTEINS.
MOST RECENTLY IT WAS FOUND THAT
PROKARYOTES SUCH AS E. COLI
ALSO HAVE THESE PROTEINS. AND
THESE ARE CALLED ANTIVIRAL
STRAND PROTEINS AND WHAT THEY
DO IS THEY HAVE A NUCLEASE THAT
CLEAVES VIRAL DNA, AND AS
RESULT CAN DEFEND E. COLI FOR
EXAMPLE AGAINST VIRUSES OF
BACTERIAL ORIGIN.
NOW, JUST TO GIVE THIS SOME
PERSPECTIVE-- BECAUSE I KNOW
THIS IS A VERY BROAD AUDIENCE--
THESE GENES ALSO BEEN
GENETICALLY LINKED TO DISEASES.
AND I KNOW PAUL LU (PHONETIC)
HAS DONE A LOT OF WORK WITH
GENETICAL LINKAGE TO DISEASES
AND THE CIITA I ALREADY
MENTIONED IS LINKED TO TYPE II
BARE LYMPHOCYTE SYNDROME. AND
NOD2 IS ONE OF THE BEST GENETIC
DEFECTS IN CROHN'S DISEASE. AND
THIS PROTEIN WHICH IS WELL
KNOWN AT NIH AND I WILL GO INTO
THIS A BIT MORE CALLED
CRYOPYRIN OR NLPRP3 LINK TO
MULTIPLE AUTO INFLAMMATORY
DISEASES.
SO WHAT IS THIS FAMILY OF
DISEASES? THESE ALL GAIN A
FUNCTION MUTATION SO NLRP3 IS
IMPORTANT FOR INFORMATION BUT
WE HAVE A GANG FUNCTION
MUTATION WHICH LEADS TO SEVERE
PHYSIOLOGICAL DISEASES RELATED
TO AN INCREASE IL-1 DENSITIES
WHICH I WILL GET INTO A LITTLE
MORE. THE TREATMENT IS IL-1
RECEPTOR ANTAGONIST OR
ANTIBODIES AGAINST IL-1.
AND INITIALLY THIS WAS THE
DISCOVERY OF A YOUNG FACULTY AT
THE TIME, NOT TO SAY THAT HE IS
OLD-- BUT IT'S BEEN QUITE A FEW
YEARS NOW-- HAL HOFFMAN AT UCSD
AND DAN AND HIS COLLEAGUE THE
TELEWORK -- AND -- DID A LOT OF
WORK ON THIS DISEASE FAMILY
INCLUDING IS MORE SEVERE
VERSIONS CALLED NOMID OR SYNCA
(PHONETIC). THESE ANTIBODIES
ARE IL-1 ANTAGONIST THAT WILL
TARGET IL-1. PATIENTS REALLY
GET BETTER WITHIN DAYS WHICH IS
REMARKABLE. BEFORE THEY WOULD
HAVE FLASHES-- IN THE LESS
SEVERE CASES TO REALLY CNS
PROBLEMS AS WELL AS SEVERE
INFORMATION, IN THIS CASE OF
THE KNEES.
SO THERE ARE MANY MUTATIONS
THAT HAVE BEEN FOUND IN THIS
DISEASE. ALL OF THESE CAN BE
TREATED BY THESE ANTIBODIES AND
THIS THE TRIUMPH OF TRANSLATING
THE BENCH TO BEDSIDE. AND MUCH
OF THIS WORK IS REALLY DONE AT
NIH.
SO, IT TURNS OUT THESE NLRS
PROTEINS WHAT THEY DO IS THEY
FORM THE MULTIMERS CALLED THE
-- RECEPTOR FOR DIFFERENT
LIGANDS INDICATED HERE AND WHAT
THEY DO IS THE ACTIVITY IN SOME
CASES WE STILL DON'T KNOW HOW
THIS IS DONE. BUT THE ACTIVATE
THE INFLAMA ZONE RECEPTOR, THIS
RECRUITS PRO CAS BASE 1 ENZYE,
WHICH ACTIVATESPRO-CASPASE 1.
AND THIS IS THE INFLAMMAZONE.
SO, ONE IMPORTANT CONCEPT IN IN
THE INFLAMMAZONE, IS IT
REQUIRES TWO STEPS. THE FIRST
THAT IS LEADING ACTIVATION TO
INFLAMMAZONE COMPONENTS FOR
EXAMPLE TLR CAN PRIME THIS AND
TLF CAN PRIME THIS MEETING THE
DESCRIPTION OF MANY
INFLAMMAZONE COMPONENTS.
AND THESE PROTEINS ARE FROM AND
THEY GO THROUGH
POST-TRANSLATIONAL ALLOCATION
THAT IS STILL THE PRIMING PHASE
SUCH AS PHOSPHORYLATION, ETC.
ALL OF THESE COMPONENTS ARE
READY TO BE ASSEMBLED IN THE
SECOND STEP IS SIGNAL 2,
ACTIVATION CAUSING THE ASSEMBLY
OF THESE INFLAMMAZONE DIFFERENT
COMPONENTS INTO THIS LARGE
COMPLEX.
AND SO THIS THEN CAUSES IL-1
SECRETION IN IO-8 AND I ALSO
MENTIONED GASTRIN B, WHICH
CLEAVED AND FORMS THE MEMBRANE
AND NOW WE HAVE THE MATURE FORM
RESULTING IN INFLAMMATION AND
IN CELL DEATH. THESE ARE TWO
DIFFERENT COMPONENTS OF THE
INFLAMMAZONE.
THIS FIELD HAS TO LOOK AT TONS
OF FUNCTIONS OF INFLAMMAZONE.
ALL OF THESE THAT I MENTIONED
HAVE ALSO BEEN DONE AT THE SAME
TIME, OR MAYBE A LITTLE BIT
LATER, BY OTHERS IN THE FIELD.
SOMETIMES A LITTLE BIT EARLIER
BY OTHERS IN THE FIELD FOR
EXAMPLE WE FOUND THAT
INFLAMMAZONE IS VERY IMPORTANT
FOR INFLUENZA AND ALSO
IMPORTANT FOR AUTOIMMUNE
DISEASES THAT ARE T CELL
MEDIATED SUCH AS EAE AND MODEL
FOR MULTIPLE SCLEROSIS, IS
IMPORTANT FOR METABOLIC
DISEASES AND OUR PAPER SHOWED
IT IS REALLY ACTIVATED BY
SATURATED FATTY ACID. THIS IS
ONE WORK DONE BY -- NOW
PROFESSOR AT OHIO STATE.
AND THEN WE HAVE PAPERS
INDICATING ITS IMPORTANCE IN
NEURONAL INFORMATION AND
INFORMATION THAT DOES NOT
REQUIRE T CELLS.
IN ADDITION WE FOUND THAT THESE
ARE REALLY IMPORTANT IN
COLITIS, COLON CANCER, ETC.
THE BROAD IMPACT OF
INFLAMMAZONE IS IN MANY
DISEASES. FOR THIS REASON
THERE ARE BILLIONS OF DOLLARS
SPENT BY PHARMA LOOKING AT
INHIBITORS OF THIS PATHWAY.
MANY OF THEM ARE LOOKING
PROMISING.
SO, WHEN THE COVID CRISIS
STARTED, WE LIKE EVERYBODY ELSE
HAD TO CLOSE DOWN OUR LAB. ONE
OF THE POSTDOCS IN MY LAB
REALLY WANTED TO STUDY COVID.
AND ASSET WE HAVE NEVER DONE
THIS. WE HAVE TO WORK ON BSL 3
FACILITIES, ETC. THE CAP WAS
UNDAUNTED. SHE WANTED TO TAKE
THE ROLES OF INFLAMMAZONES ON
COVID. THERE WERE INDICATIONS
THAT AN AND SEVERE COVID
PATIENTS THERE WAS AN INCREASE
IN IL-1 AND IL-6, AND IN
CHILDREN ONE OF THE MAIN
OUTCOMES IS INCREASES IN IL-1.
IN LONG COVID THERE IS SEQUELAE
OF IL-1.
AND IN SEVERE COVID PATIENTS,
THE RESULTS ARE MIXED. THERE
ARE A FEW GOOD PAPERS LOOKING
AT IL-1 INHIBITORS IN SEVERE
COVID WHERE THERE ARE
INDICATORS OF STRONG
INFLAMMATORY COMPONENT SUCH AS
NOT ONLY INFLAMMATORY CYTOKINES
ALSO IN QUAD RELATION PROBLEMS
AND THAT IS WHERE IL-1 SEEMS TO
BE USEFUL SO SHE WAS INTERESTED
IN LOOKING AT THIS AND MANY OF
THE STUDIES WERE DONE AFTER WE
STARTED OUR PROJECTS.
WHAT CAT WAS LOOKING AT WAS THE
SYSTEM, THE FIRST STEP OF
COVID, THE INFECTION OF THE
PRIMARY AIRWAY EPITHELIAL
CELLS. AND SCOTT -- INVENTED
THIS WHOLE SYSTEM TO LOOK AT
OTHER DISEASES IN THE CNS.
AND THIS IS A CHEAT SHEET, IN
CASE YOU WANTED TO LOOK AT
SIGNALS 1 AND 2. THERE ARE
DIFFERENT THINGS THAT ARE
ACTIVATED IN INFLAMMAZONE IN
SIGNAL 1 AND SIGNAL 2.
WHAT WE HAVE FOUND IN THIS
WHOLE SYSTEM IS THAT AIRWAY
EPITHELIAL CELLS CAN MAKE IL-1,
WHEN THEY ARE RESPONDED AND
INDUCED A PROPERTY BY SIGNAL 1
AND SIGNAL 2.
IN THIS CASE PAM3 IS SIGNAL 1
AND VAL-BOROPRO WAS SIGNAL 2.
THIS WAS THE FIRST INDICATION
THAT THE CELL TYPE CAN SECRETE
IL-1.
WE WONDERED IF COVID COULD
PARTICIPATE IN THIS SO WE
LOOKED AT SARS COVID-2
EPITHELIAL CELLS. I REMEMBER
THIS IS THE FACE OF PFU AND WE
SAW THAT SARS-COVID-2
INFECTIONS WERE ABLE TO
DUPLICATE AN INCREASE IN THE
CELL CULTURES. HOWEVER WE
LOOKED AT IL-1, WE SAW THAT
SARS-COVID-2 CANNOT INDUCE ANY
IL-1 IN THIS EPITHELIAL CELLS
AND THESE ARE THE ONES
EXPRESSING ALL THE RECEPTORS OF
SARS-COVID-2. THIS IS SIMPLY A
PROCESS CONTROL.
SO THEN WE MOVED ON. WE WANTED
TO SEE WHAT IS THE EFFECT OF
SARS COVID 2 ON HUMANS. THERE
WERE QUITE A FEW PAPERS LOOKING
AT THE INDUCTION OF
INFLAMMAZONE BY S ARS-COVID-2.
SOME REQUIRED PRIMING SIGNALS
AND SOME ANTIBODIES. NOBODY WAS
LOOKING AT JUST THE VIRUS
ITSELF. WE WANTED TO LOOK AT
THE VIRUS ITSELF AND WHAT IT
DID TO PBMC.
THE VIRUS TO GET IN BUT DO NOT
SEEM TO REPLICATE ACTIVELY. THE
VIRUS VERY QUICKLY GOES DOWN IN
PFUS.
IF WE LOOK AT EXPRESSION, WE
SAW THE SAME. THIS IS THE
EXPRESSION OF THE END PROTEIN
OF SARS-COV2, AND THE VIRUSES
NOT ACTIVELY REPLICATE ON THESE
PBMCS. WE NOTICE THAT WHEN
LOOKED AT IL-1 THERE IS NO IL-1
PRODUCTION.
SO SARS-COV2 WHEN THE
DISINFECTING PBMC DOES NOT
INDUCE INFLAMMAZONE.
WHAT WE NOTICE THIS WHEN WE
LOOK AT SARS-COV2 BY ITSELF
INDICATED HERE, IT REDUCED
RELATIVE EXPRESSION OF THE
INFLAMMAZONE RNA. ALL WERE
INDUCED BY SARS-COV2 NICELY.
WE LOOK AT THE ABILITY TO
REDUCE THE INFLAMMAZONE, THIS
IS IL-1, -- WE HAVE SARS-COV2
RIGHT HERE IN THE BLUE OUTLINE
AREA THERE IS NO IL-1.
WHAT IS REQUIRED TO CAUSE
SARS-COV2 TO INDUCE IL-1? HERE
IT IS BY ITSELF AND THEN WE
ADDED SIGNAL TO ATP, AND
FINALLY WE ARE GETTING IL-1
PRODUCE AND THIS IS VERY
RESPECTABLE IL-1, ABOUT
1000-2000 PICOGRAMS PER MIL.
CAN ONLY BE SIGNAL 1, NOT
SIGNAL 2.
IT PROVIDED THE MECHANISM OF
HOW THIS IS DONE AND SARS-COV2
IS JUST SIGNAL 1 IN PBMCS.
WHAT IS THE PATTERN RECOGNITION
MOLECULE CAUSES SARS-COV2 TO BE
SIGNAL 1?
WE DETECTED THIS ONE WHICH IS
THE ENVELOPE PROTEIN, THE E
PROTEIN. THIS TURNS OUT TO BE A
SIGNAL TO INDUCE IL-1
TRANSCRIPTION AND THIS IS E
PROTEIN AND LOOKING AT THE
FIRST STEP OF INFLAMMAZONE
INDUCTION WHICH IS IL-1
MESSAGE, MRNA PRODUCTION. AND
THE E PROTEIN WAS ABLE TO
INDUCE MRNA PRODUCTION
SUFFICIENT TO CAUSE IL-1
PROTEIN PRODUCTION AND INDEED
THAT IS WHAT WE SAW SO WE USE E
PROTEIN AND S PROTEIN AS A
NEGATIVE CONTROL. WE INCLUDE A
SIGNAL 2, WHICH IS ATP. AND WE
WERE ABLE TO SEE THAT THIS NOW
INDUCED SIGNIFICANT IL-1.
IN PBMCS, E PROTEIN IS ONE THAT
ACCESS SIGNAL 1 IN INFLAMMAZONE
ACTIVATION. SO WE WERE ABLE TO
IDENTIFY THE SPECIFIC MOLECULE
INVOLVED.
SO, THEN WE WANTED TO KNOW WE
HAVE IN AN INFECTED LUNG, YOU
HAVE THE LONG CELLS, AND THE
EPITHELIAL DEAL CELLS ARE ONE
OF THE COMPONENTS. THE SECOND
COMPONENT WILL BE THE IMMUNE
CELLS AND MANY OF THESE WOULD
BE PBMCS. THIS IS VERY HARD TO
DO WITH THE HUMAN AIRWAY
EPITHELIAL CELLS SO WE USED --
CELLS, A GOOD SOURCE OF
INFECTION BY SARS-COV2. WE
INFECTED THESE WITH SARS-COV2,
AND NOTHING HAPPENS WITH IL-1
AS I INDICATED. SO IT WE JUST
HAVE THESE CELLS SEPARATELY
THEY CANNOT PRODUCE IL-1, EVEN
THOUGH SARS-COV2 IN PBMC CAN
ACT AS SIGNAL 1.
WHEN WE CULTURE THESE TWO
TOGETHER, HOWEVER, ALL OF A
SUDDEN WE ARE SEEING VERY
RESPECTABLE IL-1. WE WERE ABLE
TO PUT THE TWO TOGETHER,
SUGGESTING THAT SOME
INTERACTION HAS TO HAPPEN
BETWEEN PBMC AND THE EPITHELIAL
CELLS TO GET SIGNAL 1.
WE WERE ABLE TO SHOW THAT THIS
IS CASPASE 1 INDEPENDENT
BECAUSE WE USE THE CASPASE 1
INHIBITOR AND I WOULD GET
NOTHING, NOT SO MUCH DEPENDING
ON NRP 3 BECAUSE WE ADDED THE
INHIBITOR, AND ONLY REDUCE BY
ABOUT 40%. SO THERE IS
SOMETHING ASIDE FROM NRP 3 WE
ARE WORKING ON THAT RIGHT NOW
AND WE HAVE SOME INDICATION BUT
IT IS NOT QUITE READY FOR PRIME
TIME. SO REALLY TWO DIFFERENT
CELL CULTURES HAVE TO COME
TOGETHER TO GET IL-1.
SO, WE WANTED TO KNOW WHAT IS
IT IN SARS-COV2-INFECTED AIRWAY
EPITHELIAL CELLS IN HUMANS
ACTING AS SIGNAL 2? WHAT WE
FOUND IS WE LOOKED JUST AT THE
CULTURE -- OF THESE INFECTED
AIRWAYS EPITHELIAL CELLS AND
WERE ABLE TO FIND THAT
SARS-COV2 RELEASES GERMLINE
DNA, ALSO MITOCHONDRIAL DNA AND
WE CAN PCR OUT SPECIFIC
MITOCHONDRIAL DNA. THESE CELLS
ARE DYING AND RELEASING DNA
FROM THE CELLS. AND WE KNOW
THAT DNA CAN BE A SIGNAL 2.
WHAT WE DID IS AGAIN TOOK VIRAL
CELLS AS A REPRESENTATIVE OF
AIRWAY CELLS AND ADDED PBMC.
THE TWO TOGETHER RELEASED IL-1,
THAT IS BECAUSE VIRAL CELLS
PRODUCE SIGNAL 2, PBMC PROVIDE
SIGNAL 1. I WANTED TO KNOW IF
THE SIGNAL 2 IS DNA. WE TREATED
THE CROSS CULTURE WITH DNA AND
SIGNAL 1 WENT WAY DOWN. AND
THEY SUGGEST THAT VIRAL CELLS
CAN RELEASE DNA AND WHEN YOU
GET RID OF THE DNA, SIGNAL 2
IS GREATLY REDUCED AND NOW WE
HAVE REDUCED IL-1 EXPRESSION.
WITHIN WANTED TO KNOW IF THIS
REALLY HAPPENS IN PATIENTS. AND
WE DID ALL SORTS OF
COMPUTATIONAL BIOLOGY THAT I
WON'T BE SHOWING YOU. WE SAW AN
INCREASE OF IL-1 IN SEVERE
COVID PATIENTS AND WE SEE
COMPONENTS OF IL-1 INCREASE,
AND WE SAW CERTAIN NLR PROTEINS
INCREASE. I WANT TO KNOW IN
PATIENTS, OUR CONTROL, A
HEALTHY CONTROLS BUT HAVE A
HEALTHY LUNG DISEASE VERSUS
COVID 19 INFECTED PATIENTS AND
THEIR LUNGS. DO WE SEE
DIFFERENCES IN THE AMOUNT OF
INFLAMMAZONE? WE INDEED SAW
THAT AND BY DOING THAT A WE
LOOK FORC ASC SPECK FORMATION.
THEY SHOW A VISIBLE SPEC AND WE
CAN COUNT HOW MANY ASC SPECKS
THEY HAVE AND WE SAW THAT COVID
CAUSES A GREAT INCREASE IN ASC
SPECS.
TO SUMMARIZE WHAT I TOLD YOU IS
WHAT WE THINK IS GOING ON IS
THAT SARS-COV2 IN FACT
EPITHELIAL CELLS, AND THE CELLS
COME DOWN HERE. WHEN THE CELLS
ARE INFECTED THEY PRODUCE IL-1
MESSAGE BUT ONLY REQUIRES
SIGNAL ONE. I SIGNAL 2, WHEN
DYING THEY REALLY DOUBLE-STRAND
DNA ACTIVATING THE INFLAMMAZONE
AND SIGNAL 2. I DID NOT GET
INTO THE SEQUELA OF ONCE YOU
GET IL-1, WE SAW IL-6, AND WE
SAW A CIRCULAR APPLICATION OF
THE INFLAMMATORY LOOP.
I SHOULD SAY AT THIS POINT THAT
WE ALSO HAVE A PAPER THAT LOOKS
AT DEATH, FOLLOWING INNATE
IMMUNITY. I WILL NOT BE
PRESENTING THAT BUT THAT IS AN
INTERESTING FINDING, WHERE WE
FOUND THE AIRWAY EPITHELIAL
CELLS THAT ARE INFECTED THEY GO
THROUGH NECROPTOSIS. AND WHEN
THEY DIE THE BYSTANDER CELLS
GOES TO APOPTOSIS, AND
DIFFERENT CELL TYPES OCCUR IN
DIFFERENT POPULATION THAT PAPER
IS NOW IN SCIENCE IMMUNOLOGY.
SO, I'VE TALKED TO YOU ABOUT
THE ROLE OF INNATE IMMUNE
RECEPTORS IN INFECTIOUS DISEASE.
AND ONE THAT HAS BEEN REALLY
IMPACTFUL ON ALL OF US. NEXT
THAT WOULD LIKE TO REALLY MOVE
INTO INNATE IMMUNE RECEPTORS ON
MICROBIOTA. I PRESENTED THIS
LAST NOVEMBER HERE AT THE NIH.
SO I KNOW THIS MAY BE A REPEAT.
SO I WILL MENTION PRIMARILY
MANY OF THE NLRS ACTIVATE
INNATE IMMUNE RECEPTORS AND IT
TURNS OUT THAT MANY ARE REDUCED
AND ATTENUATED IN MANY OF THEM
WE DO NOT WORK ON, BUT OTHER
PEOPLE HAVE FOUND THAT THE
INTERFERE WITH FOR EXAMPLE IN
TP CASE SIGNLAS, IKK SIGNALS,
ETC.
IN ONE OF THEM IT WAS FOUND
THAT THESE ARE IMPORTANT ONES,
WHEN THE SPERM DNA ARE INJECTED
INTO EGGS, THAT IS A PROCESS
WHERE YOU HAVE A BOLUS OF DNA
GOING INTO THE FOREIGN DNA. YOU
DO NOT WANT TO HAVE AN IMMUNE
RESPONSE OR INTERFERON
RESPONSE. -- -- BECOMES
IMPORTANT NOT ONLY IN THE
IMMUNE SYSTEM BUT ALSO IN THE
REPRODUCTIVE SYSTEM.
SO WE HAVE FOR A LONG TIME BEEN
STUDYING NLR 12, DOWN HERE AND
THIS PROTEIN WHICH HAS AN
ENIGMATIC ROLE BECAUSE IT ALSO
HAS BEEN FOUND TO ACTIVATE
INFLAMMAZONES UNDER SOME
CIRCUMSTANCES.
IN OUR HANDS, WHEN WE LOOKED,
AND WE LOOKED FOR OVER A DECADE
IN SOME OF THE DISEASES,
WHENEVER NRP 12 IS THERE, IT
INHIBITS MANY OF THE PROCESSES
THE COST SIGNAL TRANSDUCTION
LEADING TO CO-INFLAMMATORY GENE
EXPRESSION. I WILL FOCUS ON
THIS NRP 12 PROTEIN WHICH WE
HAVE FOUND TO BE AN INHIBITOR
OF THE NF-KB AND THE NF--
PATHWAY SO WE SEE NOTHING WITH
THE SIGNALS IN CIITA AND -- WE
LOOK FOR SIGNAL TRANSDUCTION
BECAUSE P100 IS PROCESS INTO
P52, AND WE DO NOT SEE THAT I
WE DO NOT HAVE NRP 12, THIS IS
ACTIVATED SPONTANEOUSLY.
WE MOVE THIS TO MANY DIFFERENT
MODEL SYSTEMS. REALLY CANNOT
SEE MUCH OF THE EFFECT UNTIL WE
WENT TO DSS COLITIS AND THIS IS
SIMPLY A COLITIS MODEL INDUCED
BY THIS DETERGENT LIKE CHEMICAL
DSS.
WHAT WE FOUND WAS THAT WILDCAT
DID NOT DO SO POORLY BUT THE
KNOCKOUT THE VERY POORLY
INDICATED HERE. IN IF WE LOOK
AT SUBSEQUENT COLON CANCER
FORMATIONS, WE WERE ABLE TO
SHOW THAT NRP 12 KNOCKOUT IS
VERY POORLY WITH LOTS OF
COLITIS ASSOCIATED COLON POLYPS
THIS WAS FOUND BY OUR LABS.
YEARS LATER WE REPEATED THIS
MODEL AND WERE ABLE TO SEE THAT
NRP 12 KNOCKOUT HAVE INCREASED
WEIGHT LOSS AND NRP 12 WHEN IT
IS THEIR PROTECTED MICE FROM
SEVERE COLITIS AND WE WERE ABLE
TO SEE THE SURVIVAL WAS GREATLY
LOST IN THE ABSENCE OF NRP 12.
HOWEVER THIS WAS NOT AS
DRAMATIC AS THIS CASE WHERE WE
SAW SUCH DRAMATIC DIFFERENCES.
THE ONLY DIFFERENCE BETWEEN
THESE TWO WAS THAT OUR MICE
WERE MOVED TO VERY CLEAN
FACILITY AND BECAUSE THEY
WANTED TO SAVE MONEY WE LATER
DISCOVERED ALMOST GAVE THE MICE
A VEGETARIAN DIET. ALL OF A
SUDDEN WE WERE GETTING MUCH
SMALLER DIFFERENCES BETWEEN
THESE TWO. WITHOUT THIS MIGHT
BE DUE TO THE MICROBIOME, WE
WERE LUCKY IN THAT -- WHO
STARTED THE FIRST -- FACILITY
THAT IS NIH FUNDED IN THE US IS
AT OUR INSTITUTE AND WE FOUND
THAT WHEN WE PUT THESE MYOSIN
REDIRECT ELIMINATE GERM-FREE
FACILITY THERE IS NO LONGER A
DIFFERENCE BETWEEN THESE TWO
AND THE STARTED OUR WORK IN THE
MICROBIOME.
AND LEAH WHO DID THE WORK WAS
SO CAREFUL WITH FECAL
TRANSPLANTS AND HE DISCARDED
THE DATA. SO THIS IS WHAT WE
FOUND. WHEN WE PROFILE WILD
TYPE NRP 12 IN FECAL MATERIAL,
WE WERE ABLE TO SEE THAT THE
KNOCKOUT LOSS DIVERSITY AS
SHOWN HERE AND BY COORDINATION
PLOT THEY ARE QUITE DIFFERENT.
THE FECAL MATERIAL, 16S, LOOKS
VERY DIFFERENT BETWEEN WILD
TYPE AND NRP 12 KNOCKOUT MICE.
AND WE LOOKED AT ONLY CHANGES
THAT ARE CONSISTENT BETWEEN TWO
DIFFERENT VIBARIA. THIS IS THE
DIRTY ONE AND IS THE CLEAN ONE,
AND THESE ARE LITTERMATES. HE
USED LITTERMATES I SPENT A LOT
OF MONEY ON THIS BECAUSE HAVE
TO DO SISTER/BROTHER PAIRINGS
AND BY LOOKING AT ALL OF THESE
WHAT WE FOUND IS THAT THE NRP
12 KNOCKOUT MICE HAD REDUCED
EXPRESSION OF THESE TWO ORDERS.
AND DOWN TO ONE FAMILY.WE DID
NOT KNOW MUCH ABOUT THESE
FAMILIES. IT TURNS OUT THAT
THERE WAS A PAPER FROM THE --
INSTITUTE SHOWING THAT A
PEDIATRIC PATIENT THERE IS A
REDUCTION IN EXACTLY THESE TWO
ORDERS AND IN LACTOSE SPECIES
AND SO WHAT LEO DID IS WE GOT
23 STRAINS FROM UNIVERSITY OF
MICHIGAN AND WAS ABLE TO USE
NRP 12 KNOCKOUT AND HE LOST A
LOT OF WEIGHT IN THE DSS MODEL
AND HE RECONSTITUTED THIS WITH
LACTOSE PCA AND WAS ABLE TO
RESTORE THE WEIGHT LOSS. MUCH
OF IT.
THE SAME HERE, NRP 12 KNOCKOUT
WITH BACTERIAL MEDIA VERY
SEVERE DISEASE INDEX INDICATED
HERE. WHEN HE ADDED BACK --
THESE MICE GOT A LOT BETTER.
WITHOUT THIS WAS REMARKABLE
THAT YOU COULD PUT A BACTERIA
BACK INTO THESE MICE THAT ARE
SEVERELY DEBILITATED BY DSS.
AND RESTORE THEM.
WE ALSO DID THIS IN OBESITY AND
TYPE II DIABETES, WHICH WE WILL
NOT SHOW HERE THEY WERE ALSO
PUBLISHED. LACTOSE BC WAS ABLE
TO PREVENT OBESITY AND TYPE II
DIABETES IN NRP 12 KNOCKOUTS.
WE GOT MORE FAMILIAR WITH THIS
AND THEN WE STARTED WONDERING
IF THESE DIFFERENT BACTERIA
HAVE OTHER APPLICATIONS. AND
THIS IS HOW WE STARTED THIS
PROJECT. MOSTLY BECAUSE WE
WERE FUNDED BY NIH TO LOOK AT
WAYS TO REDUCE RADIATION INJURY
DURING TERRORIST ATTACKS. THERE
IS A BIG PROGRAM AND WE HAVE
BEEN FUNDED FOR OVER A DECADE
LOOK AT THIS ANOTHER PROJECT
FINDING THAT THE TLR 6 ADAMATE
IS A WONDERFUL RADIATOR OF
RADIATION DAMAGE AND CAN HAVE A
SIGNIFICANT EFFECT EVEN A DAY
AFTER THE DAMAGE HAS OCCURRED.
AND HAL-- AND THE LAB WANTED TO
KNOW WHAT IS THE LINK BETWEEN
MICROBIOME AND RADIATION
INJURIES? SHE WAS LOOKING OUT
FOR THIS AND WE ALL KNOW
RADIATION INJURY CAN HAPPEN
DURING CANCER TREATMENT. BUT
ALSO IN ACCIDENT SUCH AS AT
CHERNOBYL.
UPON RADIATION DAMAGE AT LOWER
DOSE YOU CAN SEE HEMPLATIC
DAMAGE AND ADMITTED AS YOU CAN
SEE G.I. DAMAGE AND HIGH DOSE
YOU CAN SEE -- DAMAGE ALSO
CEREBRAL VASCULAR DAMAGE WHICH
AT THIS POINT IS ALMOST NOT
MUCH THAT ONE CAN DO.
SO WE WERE MOSTLY INTERESTED IN
THIS PHASE, G.I. DAMAGE AND
GASTROINTESTINAL DAMAGE. AND SO
WHAT SHE DID WAS SHE WAS ON THE
PAPER LOOKING AT TLR 2 AND SIX
AGONISTS PREVENTING RADIATION
DAMAGE AND THESE MICE DID NOT
RECEIVE ANYTHING EXCEPT MY
RADIATION. CONTROL MICE, 15%
SURVIVED IN THIS IS WHAT MANY
OF US WHO DO BONE MARROW
TRANSPLANT WILL SEE THAT THERE
IS A PERCENTAGE OF MICE THAT
WILL SURVIVE SO-CALLED LETHAL
RADIATION. SHE WAS INTERESTED
IN THIS GROUP. SHE WAS
WONDERING WHETHER THERE IS ANY
DIFFERENCE IN THE MICROBIOME.
SHEET OF THESE MICE VERSUS
CONTROL MICE WHICH WERE AGE
NORMALLY. THESE WERE THE MICE
AGE NORMALLY AND COMPARE THE
MICROBIOME OF THESE TWO AND
FOUND A PROFOUND DIFFERENCE IN
THEIR TWO COMPOSITIONS. SHE
REPEATED THIS AGAIN. BIT THE
SECOND EXPERIMENT ONLY BECAUSE
WE HAVE THESE MICE IN HAND, AND
FOUND THE SAME THING.
WHEN SHE PROFILE THE 16S RNA
DNA THERE WAS A MAJOR
DIFFERENCE BETWEEN THE TWO
GROUPS WHAT WE CALLED THE LEAD
SURVIVORS AND THESE CONTROLLED,
"OLD MICE."
SO SHE DID SEVERAL EXPERIMENTS
TRYING TO FIGURE OUT IS THIS A
MICROBIOME, THE CLEANEST WE
HAVE SEEN? SHE TOOK THE CONTROL
ALL MY SOURCES THE ELITE
SURVIVORS, OH TWO YEARS OF AGE
BUT THIS WAS AND TOOK THEIR
FECAL MATERIAL AND TRANSFER
THEM INTO GERM-FREE MICE. WE
ALSO DID THIS WITH JUST NORMAL
MICE KEPT IN AN SPF FACILITY
BUT THESE ARE GERM-FREE MICE
AND SHE FOUND A VERY BIG
DIFFERENCE BETWEEN THE TWO.
AND THAT IS THOSE ARE FROM ,
THE LEAD SURVIVORS WE SEE FECAL
MATERIAL FROM THE LEAD
SURVIVORS, THEY DID REMARKABLY
WELL AFTER RADIATION. THESE
WERE ALL RADIATED. I THEN WE
FOLLOWS THEIR SURVIVAL.
AND THESE ARE THE ONES THAT
RECEIVE FECAL MATERIAL FROM
JUST OLD MICE. THERE IS A BIG
DIFFERENCE IN ALSO A BIG
DIFFERENCE IN THEIR DISEASE
INDEX. SO THE ONES RECEIVED
FECAL MATERIAL FROM ELITE
SURVIVORS DID REALLY, REALLY
WELL.
FROM THOSE TWO RECIPIENT
GROUPS, AGAIN WE PROFILE THE
MICROBIOME. THEY WERE QUITE
DIFFERENT AS WELL. THESE ARE
SECOND-GENERATION. THIS OTHER
GERM-FREE MICE THAT RECEIVED
FECAL MATERIAL FROM THE LEAD
SURVIVORS VERSUS CONTROL OLD
MICE. IN WHICH HE FOUND WAS
THAT A NUMBER OF BACTERIA WERE
INCREASED IN THE LEAD SURVIVORS
INDICATED HERE, INCLUDING --.
WE WERE AGNOSTIC AT THIS POINT.
WE PUT A BUNCH OF THESE
BACTERIA INTO MICE. I
PRETREATED THE MICE BY ORAL
GABBAGE (PHONETIC), AND THEN
RADIATED THEM AND THESE ARE THE
DIFFERENT MICE THAT WERE
TREATED. PREVIOUS STUDIES HAVE
SHOWN THAT LACTOBACILLUS CAN BE
HELPFUL. WE WERE ABLE TO SHOW
THAT IF YOU TREAT MICE BEFORE
RADIATION, LACTOBACILLUS WAS
INDEED HELPFUL. BUT WHAT WAS
SURPRISING WAS THAT
LACTOVICIATE (PHONETIC), WAS
REALLY GOOD, PREVENTIVE 50% OF
THE MICE FROM DYING. WE WERE
ABLE TO SHOW THE RESTORATION OF
THE LYNPHOPOETIC SYSTEM THE
MORE GENERATIVE SYSTEM -- ALSO
LEAKAGE AT THE POINT OF THE
ARROW TO MEND LEAKAGE.
SO THERE ARE THERAPIES FOR
RADIATION SYNDROME IN THE
HEMOPLOTTING SYSTEM. NO THERAPY
FOR THE GR SYNDROME AND WE ARE
LOOKING AT SOME OF THESE
INPATIENTS.
IN THE LACHNOSPIRACEAE, WE WERE
ABLE TO IDENTIFY THREE STRAINS
THAT MADE VERY LOW AMOUNTS OF
SHORT GENE VERY ASSETS AND ONES
THAT MADE HI AMOUNTS OF SHORT
GENE FATTY ACIDS. WE GREW
THESE THREE TOGETHER AND THESE
THREE TOGETHER AND FED THEM TO
MICE AND TREATED THEM WITH
TOTAL BODY RADIATION.
THE ONES THAT RECEIVED THESE
WERE MUCH BETTER PROTECTED, AS
INDICATED HERE. THESE ARE THE
HIGH SCFA, AND WE THINK THAT
THIS SHORT SCFA MAY BE
PROTECTING THESE MICE.
BY OBTAINING PATIENT SAMPLES AT
DUKE AND AT MEMORIAL
SLOAN-KETTERING, AND ALSO AT
CORNELL, PATIENTS WHO HAD
RECEIVED RADIATION-- LOOKING AT
THEIR FECAL MATERIAL FOR AMOUNT
OF OTUS OF LACHNOSPIRACEAE AND
THE LACTOBACILLUS, AND THE
COMMISSION DISEASE-FREE LOOK
WITH PATIENTS WITH DIARRHEA
THAT LASTED LESS THAN 10 DAYS,
LESS SEVERE VERSUS THOSE WITH
DIARRHEA LASTING MORE THAN 10
DAYS AND THOSE WITH LESS SEVERE
SYMPTOMS ALSO HAD INCREASED
AMOUNTS OF LACHNOSPIRACEAE.
AND THIS OF COURSE IS A
CORRELATION. WE DO NOT REALLY
SAY THIS IS CAUSATIVE. BUT IT
IS A HYPOTHESIS THAT
LACHNOSPIRACEAE MAY BE
BENEFICIAL IN THIS GROUP.
AND SO NEXT WE WANTED TO SEE IF
SHORTEN FATTY ACID HAS
BENEFITS. AND THIS ONE,
PROPENATE, A STRONG BENEFICIAL
EFFECTS OF RADIATION AND HERE
WE GAVE SCFA CONTAINING WATER
AND THEN WE RADIATED THESE MICE
AND WE SHOWED THAT PROPENATE
PRETREATMENT WAS ABLE TO
INCREASE SURVIVAL RATE AND
REDUCE THE DISEASE INDEX.
CLINICAL SCORES. IT HAD AN
EFFECT ON BOTH THE BONE MARROW,
CAUSING BONE MARROW RESTORATION
AS INDICATED HERE. AND I DON'T
THINK I HAVE THIS SLIDE BUT IT
ALSO CAUSED G.I. RESTORATION.
IN ADDITION TO SCFA WELL KNOWN
IN THE FIELD AND SHOWN THE
OTHERS TO BE BENEFICIAL IN
RADIATION WE WANTED TO KNOW WE
CAN DO AN UNBIASED APPROACH TO
LOOK AT OTHER METABOLITES THAT
CAN BENEFIT RADIATION DAMAGE.
WE FOUND TRYPTOPHAN WAS HIGHEST
ON THE SCORE, THAT IS DIFFERENT
BETWEEN SURVIVORS, BETWEEN
ELITE SURVIVORS AND OLD MICE.
AND THIS WAS DONE BY LOOKING AT
THE METABOLITES DONE BY -- AT
UNC.
WE USED TWO DIFFERENT
TRYPTOPHAN METABOLITES. ONE
FROM THE BACTERIA. ONE FROM
THE HOST. LOOKING AT THESE
TWO, WERE ABLE TO SHOW THAT
TREATING MICE-- THIS IS ONE DAY
BEFORE RADIATION EXPOSURE--
THESE TWO WERE ABLE TO REDUCE
DISEASE INDEX AND INCREASED
SURVIVAL RATES. AND THIS
LASTED FOR OVER 300 DAYS.
SO THIS IS ABOUT HERE. SO, IN
CONCLUSION FOR THIS PART, WE
STARTED FROM INNATE IMMUNE
RECEPTORS. FOUND A GROUP OF
BACTERIA THAT WE HAVE BEEN
LOOKING AT. WE FOUND THAT THESE
BACTERIA, INCLUDING
LACHNOSPIRACEAE, CAN ALSO
REDUCE RADIATION DAMAGE.
SPECIFICALLY WE WERE ABLE TO
FIND METABOLITES, DOWNSTREAM OF
THESE BACTERIA THAT CAN PREVENT
RADIATION DAMAGE. AND RESTORE
BOTH HEMATOPOIESIS AND
INTESTINAL RECOVERY.
ONE OF THE YOUNG CLINICAL
FACTORY AT UNC USE THIS DATA.
WE STARTED A CLINICAL TRIAL
STARTING SCFA PROPIONATE AND
DIFFERENT COMBINATIONS TO LOOK
AT THE EFFECT OF REDUCING
RADIATION DAMAGE.
I WANT TO CONCLUDE BY SAYING,
NOT SHOWING YOU VERY MUCH DATA,
THAT WE ALWAYS THINK ABOUT
RECEPTORS, BEING CELL TYPE
SPECIFIC OR ADAPTIVE IMMUNE
SPECIFIC OR INNATE IMMUNE
SPECIFIC AND MOST PEOPLE
LOOKING AT INNATE IMMUNE
RECEPTORS CANNOT LOOKED AT
THEIR FUNCTIONS AND T CELLS AND
B CELLS THIS IS A SMALL NUMBER
OF PAPERS PUBLISHED BUT, WE
NOTICE THAT MANY OF THE INNATE
IMMUNE RECEPTORS ARE HIGHLY
EXPRESSED IN T CELLS AND B
CELLS.
THESE ARE SOME OF THE STARS
THAT WE HAVE DONE SHOWING THE
IMPORTANCE OF INNATE IMMUNE
RECEPTORS IN T CELLS AND B
CELLS. FOR EXAMPLE THIS ONE
ACTUALLY PREVENTS OVERZEALOUS
CD FOR T CELL RESPONSES IN BOTH
VIRUS INFECTIONS, IN THIS CASE
ACLB INFECTION AND
AUTOIMMUNITY IN IT EVENTUALLY
SHUTS DOWN THE PRO-INFLAMMATORY
RESPONSE AND WE KNOW THIS
PROTEIN ACTUALLY PROMOTES
OXIDATIVE PHOSPHORYLATION AND
INCREASES HIV REPLICATION. I
CORRELATED WITH LARGE PATIENT
SAMPLES, WHERE HIV IS INCREASED
CORRELATED WITH INCREASED
OXIDATIVE PHOSPHORYLATION
SIGNAL.
IN THIS CASE FINALLY WE FOUND
THAT THIS HAS A PROFOUND EFFECT
IN PRESERVING T CELL STABILITY.
IN ADDITION TO THIS, THIS IS A
WELL-KNOWN PATHWAY WHICH IS
CGAS AND STING. CGAS THE TEXT
DNA INDICATED HERE WHICH
PRODUCES CYCLING GNP AND GHP,
ACTIVATING STING TO CAUSE
INTERFERENCE ANOTHER CYTOKINE
INDUCTION. THIS IS FOUND TO
HAVE MANY DIFFERENT ROLES,
INCLUDING PROMISING EFFECTS IN
MANY CANCER PRECLINICAL MODELS
OF CANCER BECAUSE YOU GET LOTS
OF INTERFERON PRODUCTION LOTS
OF CDA ACTIVATION, ETC., IN
THIS GOES ON BOTH IN THE
MYELOID CELLS AS WELL AS THE
CANCER CELLS THEMSELVES.
HOWEVER, WHEN THIS IS USED IN
MONOTHERAPY OF STING IN CANCER
FOR CLINICAL TRIAL, RESULTS
HAVE BEEN VERY DISAPPOINTING.
THE OTHER THING IS, IN MOST
MOUSE MODELS, STING IS TO BE
INJECTED INSIDE THE TUMOR. THIS
WILL BE VERY DIFFICULT TO
EXECUTE. WE HAVE A PAPER
SHOWING THAT WHAT TURNS OUT TO
BE THE CASE IS THAT STING CAN
ACTIVATE B CELLS; BUT THE
POPULATION YOU PROBABLY DON'T
WANT, THESE B REGULATORY CELLS.
THESE ARE INDUCED BY STING
ACTIVATION TO PRODUCE AN IMMUNE
SUPPRESSIVE CYTOKINE ILK 35,
WHICH REDUCES NLK PROLIFERATION
AND STING CAN HAVE OUT A
NEGATIVE EFFECT ON THE IMMUNE
SYSTEM TO BLOCK NK CELL
TOXICITY AND THIS WAS PUBLISHED
A YEAR AND A HALF AGO.
SO WE WANTED TO COME UP WITH A
THERAPY. ONE OF THE THERAPIES
THAT -- AND HIS POSTDOC WERE
KIND ENOUGH TO RECRUIT US AS
IMMUNOLOGISTS, SO THIS PAPER
WAS JUST PUBLISHED IN -- WHAT
THEY HAVE DONE IS TAKING THE
NATURAL CONFIGURATION OF CGAS
COMPLEX WITH C-CAMP A TETRAMER.
THEY TOOK A FULL-LENGTH STING
AND CONJUGATED TO AN ALGOMERE,
IN ARTIFICIAL THETRAMIZATION,
AND THIS FORMS A TETRAMER, AND
YOU HAVE AN ACTIVATED GENE THAT
GOES TO CANCER CELLS AND WE
FOUND THAT BOTH HUMAN, AND
MOUSE CANCER AND WAS ABLE TO GO
INTO ALL SORTS OF CANCER CELLS.
WHAT WE DO KNOW IS THAT CANCER
EVEN THOUGH STING IN CANCER CAN
HELP, IT TURNS OUT THAT THE
MAJORITY OF CANCERS HAVE LOSS
OF STING, WITH THE INNOVATION
(CORRECTION) INHIBITION OF
STING PATHWAY ITSELF -- WE
WANTED TO KNOW IF WE COULD USE
THIS UNI-STING TO ACTIVATE
STING IN CANCER AND WAS UNIQUE
IS THIS TETRAMERIZED STING,
EIGHT INDUCE THE INTERFERE
PATHWAY IS INDICATED HERE BUT
DID NOT INDUCE MUCH OF THE NFK
PATHWAY. WE STILL DO NOT KNOW
WHY BUT NF-KB CAN BE
INFLAMMATORY AND PRO CANCER AND
WAY BACK 20 YEARS AGO WHEN THE
LAB SET SHOWN NF-KB IS ACTUALLY
PRO TUMOR INCLUDING THE LAB OF
MY NEIGHBOR AL BALDWIN. THAT
WAS SHOWN YEARS AGO. IN THE UNI
STING IT INDUCED INTERFERON AND
WANTED TO KNOW IF THIS UNI
STING CAN BE USEFUL IN
DIFFERENT TUMOR SYSTEMS THAT DO
NOT HAVE STING ACTIVATION IN
THIS IS ONE OF THE CELL LINE, A
TRIPLE NEGATIVE BREAST CANCER
AND THIS IS METASTATIC LIVER
CANCER. IN BOTH CASES, WE JUST
DELIVERED STING AGONIST, THE
CGAMP, AND WE DELIVERED THE
STING NANOPARTICLES HE DID WELL
AND WE FOLLOWED UP TO ABOUT 60
DAYS IN THIS TUMOR SYSTEMS.
SO TO CONCLUDE, WE THINK MANY
OF THESE INNATE IMMUNE
RECEPTORS SUCH AS STING
CONNECTIVITY REVELATORY
PATHWAYS BUT THIS MAY BE ONE,
THE UNI STING, AND ARTIFICIAL
STING MADE BY BYPASSING SOME OF
THESE REGULAR PATHWAYS. IT IS
IN ITSELF A TETRAMERIZED STING,
DELIVERED IS A LIQUID
ANTIPARTICLE AND THESE LIQUIDS
ARE NOT KNOWN TO GO INTO T
CELLS AND B CELLS IN HIGH
AMOUNTS AND IT WAS TESTED IN
MULTIPLE CANCERS INCLUDING MANY
OF THESE AND IT DOES NOT
REQUIRE ENDOGENOUS ACTIVE STING
IN THE TUMOR AND ACTIVATES THE
NRF 3 PATHWAY WITHOUT
ACTIVATING THE TUMOR PROMOTING
NFKB PATHWAY IN CONCLUSION I
WANT TO SHOW YOU AND THIS IS
THE INNATE RECEPTORS CAN HAVE
MANY DIFFERENT EFFECTS
INCLUDING EFFECTS ON
INFECTIONS, INFLAMMATION,
AUTOIMMUNE DISEASES METABOLIC
DISEASES CANCER AS VACCINES
AFFECTING MICROBIOME. AND ALSO
IN T CELLS AND B CELLS WHICH
WERE FOUND TO HAVE MANY OF
THESE INNATE IMMUNE RECEPTORS.
I WANT TO REALLY THANK THE
PEOPLE WHO ARE INVOLVED. OUR
EARLY WORK AT NRP 12 WAS DONE
BY THESE FORMER MEMBERS. IN TWO
OF THESE ARE NOW FACULTY AT
DIFFERENT INSTITUTIONS AND TWO
ARE IN PHARMA. AND MANY OF HIS
PEOPLE ARE STUDYING T CELLS AND
B CELLS IN SOME ARE FACULTY IN
JAPAN AND THE NETHERLANDS. AND
-- DID ALL THE SARS-COV2 WORK.
AND HOW DID THE MICROBIOME WORK
TOGETHER WITH JUNE BRICKY
(PHONETIC), THESE ARE SOME OF
THE COLLABORATORS. JULIA HELPED
US A LOT WITH THE B CELL WORK
THAT I MENTIONED AND BELFOR, I
MENTION HIM AND -- AT DUKE AND
SLOAN-KETTERING AND CORNELL.
AND ANOTHER ACKNOWLEDGMENT.
THESE ARE THE TWO PEOPLE WHO
DESPITE COVID WENT TO DUKE. FOR
ALL SORTS OF REASONS WE CANNOT
USE THE BSL FACILITY AT UNC. WE
HAD TO GO TO DUKE. THEY DROVE
2500 MILES TO DO THESE
EXPERIENCES I GOT TRAINED IN
THIS IS -- -- AND THESE ARE THE
MANY INVESTIGATORS WHO HELPED
US. I MENTIONED SCOTT -- DUKE,
UNIVERSITY OF MICHIGAN AND NIH
ESPECIALLY. AND IU YING
(PHONETIC) WHO HELPED WITH A
LOT OF COMPUTATIONAL BIOLOGY.
THANK YOU VERY MUCH FOR YOUR
INVITATION. IT IS A GREAT
HONOR.
>> [APPLAUSE]
>> THERE'S MICROPHONES IN THE
STEPS CORRIDOR.
>> DR. TING: I WAS TOLD THAT ON
THERE MAY BE QUESTIONS.
>> I HAVE A QUESTION ABOUT THE
RADIATION PRODUCTION STORIES
ARE IN BENEFIT OF COMBINING
SCFA AND (INDISCERNIBLE).
>> DR. TING: IT HAS TO WORK
BEFOREHAND WHICH IS GREAT FOR
CANCER PATIENTS BECAUSE YOU
KNOW THEY WILL COME IN FOR
TREATMENT. WE ACTUALLY ENROLLED
-- WE PREPARE THE SAMPLES FOR
THE CLINICAL LAB. WE HAVE
QUITE A FEW WHO ALREADY CAME IN
AND GAVE SAMPLES. WE WOULD KNOW
THAT SOON.
YES JAKE?
>> HI. OVER HERE. IN TYPE I
INTERFERENCE, THERE IS A
DIFFERENT FUNCTION BETWEEN
ALPHA AND BETA. UNDERSTAND THAT
INTERFERE ALPHA IS MADE
PRIMARILY BY PDCS, AS OPPOSED
TO A DIFFERENT BETA MADE BY
MANY CELLS WHEN YOU'RE INDUCED
WITH STING. THEY BE MORE
EFFECTIVE AT LEAST IN HUMANS IN
INDUCING CDA T CELLS, MAY BE
MORE EFFECTIVE IN CANCER. THE
QUESTION IS DOES THE UNI STING
ACTIVATE PDCS TO MAKE
INTERFERON ALPHA? DO YOU HAVE
ANY INFORMATION?
>> DR. TING: GREAT QUESTION. WE
DID NOT LOOK AT THAT. WE DID
LOOK AT MYELOID CELLS NOT
FOCUSING ON THE PDCS. WE
FOCUSED ON INTERFERON BETA NOT
SO MUCH ALPHA INTERESTED
MOSTLY. WE GET RID OF CDAS IF
THEY DO NOT WORK. WE DID NOT
LOOK AT PDCS.
>> APPARENTLY THERE'S A
DIFFERENCE BETWEEN MICE AND
HUMANS IN THAT REGARD. ALPHA
AND BETA HAVE MORE DIFFERENCES
IN HUMANS THAN THEY DO IN MICE.
>> DR. TING: YEAH WE DIDN'T DO
THIS OBVIOUSLY IN HUMANS. BUT
WE DID LOOK AT HUMAN CANCERS TO
SEE IF IT HAS THE SAME EFFECT.
AND FOR THE MEASUREMENTS SUCH
AS INTERFERON BETA AND ALL THE
SIGNALS IT DID EXACTLY THE SAME
SO WE USE TWO DIFFERENT HUMAN
CANCERS. AND I THINK THREE OR
FOUR DIFFERENT MOUSE CANCERS.
THE EFFECT ON INTERFERON WAS
SIMILAR.
WE DID A LOT OF WESTERN BLOCKS.
I TOOK THEM ALL OUT BECAUSE I
THOUGHT PEOPLE WILL BE GOING
NUTS. THANK YOU.
>> THANK YOU.
>> THANK YOU THANK YOU FOR SUCH
A HAVE A STALKER MY INITIAL
IMPRESSION OF SEN. YOU TALK WAS
WOW! YOU COVERED SO MANY AREAS
IN CLINICAL AND BASICS.
I WAS INTRIGUED BY YOUR
OBSERVATION THAT MANY OF THE
INFLAMMAZONE COMPONENTS ARE
ACTUALLY BLOCKING THE
INTERFERON INDUCTION. TWO-PART
QUESTION. I WONDER IF IT HAS
ANY EFFECT ON THE DOWNSTREAM
INTERFERON EFFECT. AFTER STAT
1, 2 ACTIVATION. DOES THAT
BLOCK THAT AS WELL? OR IS IT
MORE OF A REDUCTION ON THE
INTERFERON?
>> DR. TING: WE DO SEE STAT
CHANGES. WE IMAGINE THAT IS
FROM THE INTERFERON UPSTREAM.
WE HAVE AN NLRX 1. WHICH WE
ALWAYS HAVE TO CAJOLE PEOPLE IN
THE LAB TO WORK ON PROJECTS BUT
WE HAVE ONE THAT ACTUALLY
BLOCKED MATS, THE ONCE FROM THE
-- FUNCTION. AND THERE'S A
NUMBER OF LABS THAT ARE SHOWN
THE SAME BUT AGAIN THAT IS
UPSTREAM. WHAT WE ARE LOOKING
AT IS MOSTLY UPSTREAM.
WE HAVE NOT SEEN DOWNSTREAM
INHIBITION. WE DID SEE TBK
INHIBITION, OTHER PEOPLE HAVE.
>> SO IT IS POSSIBLE?
>> DR. TING: YEAH IT IS
POSSIBLE.
>> THE OTHER QUESTION IS SINCE
INDUCTION INTERFERONS ACTUALLY
PLAY A MAJOR ROLE IN VACCINE
EFFECTS, I WONDER WHETHER THE
INFLAMMAZONE IT BE INVOLVED IN
SOME OF THE VACCINE RESPONSE,
AND WHETHER IT IS SOMETHING
WORTHWHILE THINKING ABOUT.
WHETHER YOU BLOCK INFLAMMAZONE
AND MAYBE THAT WILL ENHANCE
VACCINE EFFICACY IS.
>> DR. TING: YES ONE OF THE
BEST ONES-- I DON'T THINK
ANYBODY HAS BEEN THINKING THAT
WAY. BUT ONE OF THE BEST
EXAMPLES OF INFLAMMAZONE
WALKING IS -- YOU ARE
ACTIVATING AND INTERFERON GOES
DOWN BUT I CANNOT THINK OF A
SINGLE STUDY THAT USES THAT TO
TAKE ADVANTAGE OF IT FOR
VACCINE PURPOSES. PROBABLY
BECAUSE ALL OF THESE OTHER
CYTOKINES, IL-1 IS PROBABLY
NECESSARY FOR VACCINE RESPONSES
WELL.
>> THANK YOU.
>> DR. TING: I THINK THAT WILL
BE THE LAST QUESTION. THANK
YOU VERY MUCH FOR ATTENDING.
AND WE WILL HAVE A RECEPTION
JUST OUTSIDE. AS YOUR REWARD
FOR SHOWING UP IN PERSON.
ANOTHER ROUND OF APPLAUSE.
>> [APPLAUSE]
>> [END]