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>> WELCOME TO OUR ANNUAL 

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KUAN-TEH JEANG MEMORIAL 

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LECTURE.  YOU MAY HAVE NOTICED 

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00:00:14,017 --> 00:00:18,955
THAT IT IS NO LONGER 

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ASIAN-AMERICAN, NATIVE 

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HAWAIIAN, PACIFIC ISLANDER 

7
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MONTH.  BUT,  IT'S SORT OF A 

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RUNNING JOKE THERE ARE SO MANY 

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ACCOMPLISHMENTS BY THE AANPI 

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COMMUNITY WE CANNOT FIT THEM 

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ALL IN ONE MONTH SO WE HAVE HAD 

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THE KUAN-TEH JEANG MEMORIAL 

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LECTURE IN THE FIRST WEEK OF 

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JUNE. 

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I WOULD LIKE TO START OFF WITH 

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SOME REMEMBRANCES OF KUAN-TEH 

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JEANG IN WHOSE HONOR WE ARE 

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HAVING THIS TALK. 

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NEXT SLIDE PLEASE.

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TEH WAS BORN IN 1958 IN 

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TAICHUNG, TAIWAN AND SPEND HIS 

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CHILD AND LYBIA. CAME TO THE 

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UNITED STATES IN 1970. HE WAS A 

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TRUE CITIZEN OF THE WORLD, HE 

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EARNED HIS MD AND PHD AT JOHNS 

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HOPKINS AND WENT TO STUDY WITH 

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JOHN HAYWARD. 

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CAME TO NIH IN 1985 SAME YEAR I 

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DID AND DID POSTDOCTORAL 

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FELLOWSHIP WITH THE LATE DR. 

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GEORGE CORY.  AND THAT IS 

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ANOTHER CONNECTION WE HAVE. 

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GEORGE CORY IS ACTUALLY THE 

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REASON I ENDED UP AT NIH. HE 

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GAVE A WONDERFUL TALK AT 

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HOPKINS WHEN I WAS THERE AND HE 

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SAID NIH IS THE MOST WONDERFUL 

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PLACE TO BE. IT RESEARCHES ONE 

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OF YOUR TOP PRIORITIES, THERE 

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IS NO BETTER PLACE THAN THE NIH 

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INTRAMURAL RESEARCH PROGRAM. 

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SO AFTER HIS POSTDOCTORAL 

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FELLOWSHIP, HE MOVED TO THE 

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NATIONAL INSTITUTE OF ALLERGY 

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AND INFECTIOUS DISEASES AND 

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BECAME KEYS OF THE MOLECULAR 

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VIROLOGY SECTION, IN THE 

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LABORATORY OF MOLECULAR 

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MICROBIOLOGY, WHERE HE STUDIED 

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THE HUMAN IMMUNODEFICIENCY 

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VIRUS AND THE RELATED BUYERS 

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HTLV-1. 

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HE WAS THE EDITOR-IN-CHIEF OF 

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RETROVIROLOGY. AND LATER IN THE 

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NIH VIROLOGY INTEREST GROUP AND 

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A LEADER IN THE CHINESE SOCIETY 

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OF BY SCIENTISTS IN AMERICA IN 

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A BIG ADVOCATE FOR RACIAL 

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MINORITY GROUPS AND PERSONS 

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WITH DISABILITIES. 

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AND WE CONTINUE TO CHERISH HIS 

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MEMORY AND LEGACY.  THIS IS A 

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PICTURE OF HIS FAMILY. HIS 

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FAMILY COULD NOT BE HERE TODAY 

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BECAUSE THERE ACTUALLY IN 

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TEXAS, CELEBRATING THE END OF 

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THE RESIDENCY OF ONE OF HIS 

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DAUGHTERS. 

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AND, IF YOU GET A CHANCE, WE 

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ACTUALLY HAVE A MEMORIAL GARDEN 

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IN BETWEEN BUILDING 31 AND 

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BUILDING 33.  AND YOU CAN SEE 

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00:03:31,514 --> 00:03:36,486
THAT AT YOUR LEISURE. 

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I WOULD LIKE TO TURN OVER THE 

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PODIUM TO DAVID RICE, FROM OUR 

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OFFICE OF EQUITY, DIVERSITY AND 

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INCLUSION WHO WOULD LIKE TO SAY 

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A FEW WORDS ABOUT THE OCCASION. 

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>> [APPLAUSE]

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>> THANK YOU DR. OWENS. IT
IS 

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00:03:57,507 --> 00:04:00,510
MY PLEASURE TO BE HERE. WHILE 

82
00:04:00,510 --> 00:04:01,077
VIEWING YOUR SLIDES EARLIER 

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TODAY I FELT THAT YOU AND DR. 

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PAN-YUN TING, 1985. THAT IS 

85
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WHEN I WAS BORN. AND IT IS 

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GREAT THAT THE WORK AT NIH HAS 

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BEEN GOING ON FOR A LONG TIME, 

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AND MANY YEARS TO COME; THANK 

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00:04:28,371 --> 00:04:29,005
YOU AGAIN FOR ALLOWING US TO BE 

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00:04:29,005 --> 00:04:29,639
HERE AND INVALUABLE PARTNERS OF 

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THE OFFICE OF INTRAMURAL 

92
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RESEARCH, YOUR SUPPORT AND 

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COLLABORATION IN THE OFFICE OF 

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DIVERSITY, EQUITY AND INCLUSION 

95
00:04:33,209 --> 00:04:41,050
ARE DEEPLY APPRECIATED. 

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AS WE MOVED TO THE 

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ASIAN-AMERICAN, PACIFIC 

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HAWAIIAN AND NATIVE AMERICAN 

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00:04:42,552 --> 00:04:44,687
MONTH WE FOCUS ON TWO KEY 

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POINTS IN VERSE WE CELEBRATE ON 

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00:04:53,629 --> 00:04:59,302
KUAN-TEH JEANG -- I NEVER HAD A 

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00:04:59,302 --> 00:05:03,706
CHANCE TO MEET HIM. BUT MANY OF 

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00:05:03,706 --> 00:05:04,340
THE ROOM HAVE AN ONLINE TODAY, 

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ONE OF THE LEADING SCIENTISTS 

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IN BIOLOGY. 

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HE DEDICATED HIS LIFE TO 

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SCIENCE.  BUT HE WAS ALSO A 

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FIERCE ADVOCATE FOR 

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REPRESENTATION OF ASIAN 

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AMERICAN, AND LEADERSHIP 

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POSITIONS. AT THE OFFICE OF 

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EQUITY, DIVERSITY AND INCLUSION 

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WE ARE COMMITTED TO CONTINUING 

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THIS LEGACY BY DEVELOPING 

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STRATEGIES WORKING WITH OUR 

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PARTNERS IN THE NIH AND THE 

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BIOMEDICAL RESEARCH ENTERPRISE 

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AND CREATE PATHWAYS FOR FUTURE 

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GENERATIONS FOR ASIAN AMERICANS 

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TO ACHIEVE HIS VISION FOR MORE 

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ASIAN AMERICANS IN SCIENTIFIC 

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LEADERSHIP POSITIONS SOME OF 

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YOU MAY OR MAY NOT KNOW I CAN 

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SEPTEMBER 2022 OUR OFFICE IN 

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BARNSTABLE THE NATIONAL CANCER 

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INSTITUTE AND THE NATIONAL 

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INSTITUTE OF MENTAL HEALTH, AND 

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THE NATIONAL INSTITUTES OF 

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MINORITY HEALTH AND HEALTH 

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DISPARITIES PUBLISHED AN 

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ARTICLE ON THE FRONTIER JOURNAL 

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EXAMINING THE ASIAN-AMERICAN 

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LEADERSHIP GAP. IF YOU HAVE NOT 

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SEEN IT, GO AHEAD AND REVIEW 

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THE ARTICLE. 

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ONE OF THE KEY RECOMMENDATIONS 

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FROM THE ARTICLE, WHICH WAS TO 

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IMPROVE WORKPLACE CULTURE TO 

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REFLECT ASIAN-AMERICAN 

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WORKPLACE EXPERIENCE 

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ACCURATELY, THIS RECOMMENDATION 

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LEADS TO MY SECOND WEEK OF 

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REFLECTION THIS YEAR THE 

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ASIAN-AMERICAN NATIVE AMERICAN, 

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HAWAIIAN PACIFIC ISLANDER'S 

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THEME WAS EMBRACING BELONGING, 

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HONORING LONG-STANDING 

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TRADITION WHILE EMBRACING NEW 

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ONES. 

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AS YOU HAVE SEEN IN THE MONTH 

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OF MAY, THERE WERE NUMEROUS 

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EVENTS ACROSS NIH FOR INSTANCE 

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THE INSIDE LECTURE BY DR. 

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MURPHY WHERE WE EXPLORE THE 

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CRUCIAL IMPORTANCE OF 

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DEVELOPING SOCIAL CONNECTIONS 

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AND ADDITIONALLY JUST THIS PAST 

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WEEK I BELIEVE ON THURSDAY THE 

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BELONGING EVENT HOSTED BY THE 

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KOREAN WOMEN SCIENTISTS 

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ASSOCIATION WAS AMAZING, THE 

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MUSIC FOOD AND DISCUSSION 

163
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INVOLVED THERE WERE MANY OTHER 

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EVENTS ACROSS THE INSTITUTES 

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AND CENTERS, THAT CONTRIBUTED 

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TO THE SUCCESS OF THESE YEAR'S 

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ASIAN-AMERICAN MONTH, TO 

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IMPROVE THE CULTURE FOR 

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ASIAN-AMERICAN, NATIVE HAWAIIAN 

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PACIFIC ISLANDERS. 

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HOWEVER A WORKING COMMITMENT 

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CANNOT STOP AFTER ONE MONTH 

173
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MUST EMBRACE THE IDEA  THAT 

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WERE CULTURE SHOULD REFLECT 

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EXPERIENCES OF NOT ONLY THE 

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ASIAN-AMERICAN, NATIVE 

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AMERICAN, PACIFIC ISLANDERS, 

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BUT ALL UNDERREPRESENTED 

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COMMUNITIES EVERY SINGLE DAY OF 

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THE YEAR, 365 DAYS AND 366 DAYS 

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ON THE LEAP YEAR.

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IN CONCLUSION WHILE WE 

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CELEBRATE THE ACKNOWLEDGMENTS 

184
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OF ASIAN-AMERICAN, NATIVE 

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AMERICAN, PACIFIC ISLANDERS IN 

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00:07:52,842 --> 00:07:53,476
THIS COMMUNITY WE IT THE OFFICE 

187
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OF DIVERSITY AND INCLUSION, WE 

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00:07:55,444 --> 00:07:56,979
PLAN ON CARRYING OUT HIS LEGACY 

189
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AIMING TO ENSURE FUTURE 

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GENERATIONS OF ASIAN-AMERICAN, 

191
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NATIVE AMERICAN, PACIFIC 

192
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ISLANDERS HAVE INEQUITABLE 

193
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PATHWAY INTO SCIENTIFIC 

194
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LEADERSHIP. 

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OUR CALL TO ACTION FOR EACH OF 

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00:08:04,687 --> 00:08:12,661
YOU HERE IS TO HELP NIH CARRY 

197
00:08:12,661 --> 00:08:13,262
OUT THIS MISSION BY ENSURING 

198
00:08:13,262 --> 00:08:16,766
THE WORKPLACE CULTURE FOR ALL 

199
00:08:16,766 --> 00:08:19,135
COMMUNITIES. AND THIS IS FOR 

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EVERYONE HERE, EVERYONE ONLINE 

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AND EVERYONE WITHIN THE 

202
00:08:20,269 --> 00:08:22,204
BIOMEDICAL RESEARCH ENTERPRISE. 

203
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AGAIN THANK YOU DR. OWENS FOR 

204
00:08:24,573 --> 00:08:25,074
ALLOWING OUR OFFICE TO 

205
00:08:25,074 --> 00:08:25,674
PARTICIPATE TODAY AND I WILL 

206
00:08:25,674 --> 00:08:26,242
HAND IT BACK OVER TO YOU TO 

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INTRODUCE DR. JENNY PAN-YUN 

208
00:08:27,643 --> 00:08:29,111
TING. 

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>> [APPLAUSE]

210
00:08:35,551 --> 00:08:36,685
>> IT IS MY PLEASURE TO 

211
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INTRODUCE OUR 2024 KUAN-TEH 

212
00:08:38,621 --> 00:08:41,123
JEANG MEMORIAL LECTURE, DR. 

213
00:08:41,123 --> 00:08:50,666
JENNY PAN-YUN TING. 

214
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JENNY PAN-YUN TING WAS BORN IN 

215
00:08:59,408 --> 00:09:03,412
BANGKOK THAILAND, SHE CAME TO 

216
00:09:03,412 --> 00:09:04,980
THE UNITED STATES AND STUDIED 

217
00:09:04,980 --> 00:09:15,424
IT PHD FROM NORTHWESTERN 

218
00:09:16,058 --> 00:09:16,592
UNIVERSITY IN IMMUNOLOGY AND 

219
00:09:16,592 --> 00:09:17,226
THAT HER POSTDOCTORAL TRAINING 

220
00:09:17,226 --> 00:09:17,860
AT THE UNIVERSITY OF CALIFORNIA 

221
00:09:17,860 --> 00:09:18,461
AND DUKE UNIVERSITY JOIN THE 

222
00:09:18,461 --> 00:09:20,596
FACULTY OF THE UNIVERSITY OF 

223
00:09:20,596 --> 00:09:21,230
NORTH CAROLINA SCHOOL OF 

224
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MEDICINE IN CHAPEL HILL.  SHE 

225
00:09:23,265 --> 00:09:23,899
CURRENTLY HOLDS APPOINTMENTS AS 

226
00:09:23,899 --> 00:09:27,503
THE WILLIAM RAND KEENAN PROF. 

227
00:09:27,503 --> 00:09:31,407
OF GENETICS, DIRECTOR OF THE 

228
00:09:31,407 --> 00:09:32,541
CENTER FOR TRANSLATIONAL 

229
00:09:32,541 --> 00:09:34,643
IMMUNOLOGY, AND CODIRECTOR OF 

230
00:09:34,643 --> 00:09:35,544
THE INFLAMMATORY DISEASES 

231
00:09:35,544 --> 00:09:46,088
INSTITUTE.  DR. PAN-YUN TING'S  

232
00:09:47,356 --> 00:09:47,857
HAS BROUGHT INTEREST IN THE 

233
00:09:47,857 --> 00:09:48,424
APPLICATION OF CUTTING-EDGE 

234
00:09:48,424 --> 00:09:50,092
IDEAS AND TECHNOLOGIES TO THE 

235
00:09:50,092 --> 00:09:51,260
STUDY OF DISEASE RELEVANT 

236
00:09:51,260 --> 00:09:54,763
ISSUES. MAJOR DIRECTIONS 

237
00:09:54,763 --> 00:09:55,297
INCLUDE INNATE IMMUNITY, 

238
00:09:55,297 --> 00:09:58,134
DENDRITIC CELL FUNCTION, CELL 

239
00:09:58,134 --> 00:10:01,537
DEATH, SIGNAL TRANSDUCTION, 

240
00:10:01,537 --> 00:10:03,038
GENE DISCOVERY AND A PLETHORA 

241
00:10:03,038 --> 00:10:05,741
OF OTHER AREAS. 

242
00:10:05,741 --> 00:10:07,877
CLINICAL ISSUES OF INTEREST 

243
00:10:07,877 --> 00:10:10,646
INCLUDE MULTIPLE SCLEROSIS, 

244
00:10:10,646 --> 00:10:13,682
CANCER, AUTOIMMUNE DISEASES, 

245
00:10:13,682 --> 00:10:14,717
INFECTION AND INFLAMMATION. DR. 

246
00:10:14,717 --> 00:10:20,556
PAN-YUN TING HAS OVER 300 

247
00:10:20,556 --> 00:10:21,123
SCIENTIFIC PUBLICATIONS AND 

248
00:10:21,123 --> 00:10:21,557
NUMEROUS AWARDS AND 

249
00:10:21,557 --> 00:10:28,330
RECOGNITIONS.  INCLUDING BEING 

250
00:10:28,330 --> 00:10:28,864
PRESIDENT OF THE AMERICAN 

251
00:10:28,864 --> 00:10:36,939
ASSOCIATION OF IMMUNOLOGISTS. 

252
00:10:36,939 --> 00:10:37,506
AN ELECTION TO THE NATIONAL 

253
00:10:37,506 --> 00:10:39,275
ACADEMY OF SCIENCES.  HER 

254
00:10:39,275 --> 00:10:39,909
LECTURE FOR TODAY IS ENTITLED: 

255
00:10:39,909 --> 00:10:40,476
THE BROAD IMPACT OF INNATE 

256
00:10:40,476 --> 00:10:41,010
IMMUNE RECEPTORS IN VIRAL 

257
00:10:41,010 --> 00:10:41,477
INFECTION, CANCER AND 

258
00:10:41,477 --> 00:10:45,080
AUTOIMMUNITY. 

259
00:10:45,080 --> 00:10:49,018
LET'S GIVE A BIG NIH WELCOME TO 

260
00:10:49,018 --> 00:10:51,020
DR. JENNY TING. 

261
00:10:51,020 --> 00:10:52,788
>> [APPLAUSE]

262
00:10:52,788 --> 00:10:56,058
>> DR. PAN-YUN TING: THANK
YOU 

263
00:10:56,058 --> 00:10:59,528
SO MUCH DR. OWENS.  IS SUCH AN 

264
00:10:59,528 --> 00:11:00,062
HONOR TO BE HERE TO GIVE 

265
00:11:00,062 --> 00:11:09,171
TODAY'S LECTURE.  I'VE BEEN AT 

266
00:11:09,171 --> 00:11:13,642
NIH PROBABLY 40 TIMES.  GOT TO 

267
00:11:13,642 --> 00:11:14,243
KNOW THIS IS DATED AND REALLY 

268
00:11:14,243 --> 00:11:16,178
LOVE THE PEOPLE WHO ARE HERE.  

269
00:11:16,178 --> 00:11:16,745
AND TODAY LIKE I SAID IS A 

270
00:11:16,745 --> 00:11:17,313
GREAT HONOR TO GIVE THE 

271
00:11:17,313 --> 00:11:19,281
MEMORIAL LECTURE FOR KUAN-TEH 

272
00:11:19,281 --> 00:11:28,991
JEANG -- WHO ALSO WAS FROM 

273
00:11:28,991 --> 00:11:34,196
TAIWAN, AND LIVED IN LIBYA.  

274
00:11:34,196 --> 00:11:35,664
OBVIOUSLY A GENIUS LEVEL 

275
00:11:35,664 --> 00:11:39,201
RESEARCHER.  GOT HIS PHD AT THE 

276
00:11:39,201 --> 00:11:41,537
AGE OF 25. 

277
00:11:41,537 --> 00:11:43,172
HE MARRIED HIS WIFE, FELLOW 

278
00:11:43,172 --> 00:11:46,242
GRADUATE STUDENT.  THESE ARE 

279
00:11:46,242 --> 00:11:46,909
HIS RESEARCH, STARTING FROM HIS 

280
00:11:46,909 --> 00:11:51,280
WORK ON C AND B GENE RELATIONAL 

281
00:11:51,280 --> 00:11:56,385
LATER COMING TO NIH.  HE WAS AT 

282
00:11:56,385 --> 00:12:01,590
NIH FOR 27 YEARS, AND DID MAJOR 

283
00:12:01,590 --> 00:12:02,191
SEMINAL DISCOVERIES ABOUT THE 

284
00:12:02,191 --> 00:12:10,766
ROLE OF TAT AND HLIV, AND ALSO 

285
00:12:10,766 --> 00:12:12,534
REVELATORY DNA AND HE WAS 

286
00:12:12,534 --> 00:12:13,102
BLOSSOMING, MAKING A TON OF 

287
00:12:13,102 --> 00:12:15,237
CONTRIBUTION IN THIS AREA. 

288
00:12:15,237 --> 00:12:16,905
AS WAS MENTIONED BY DAVID AS 

289
00:12:16,905 --> 00:12:23,712
WELL, HE WAS A CHAMPION AT THE 

290
00:12:23,712 --> 00:12:24,246
API, AND PRESIDENT OF THE 

291
00:12:24,246 --> 00:12:24,713
SOCIETY OF CHINESE BY 

292
00:12:24,713 --> 00:12:27,283
SCIENTISTS IN AMERICA. WELL 

293
00:12:27,283 --> 00:12:29,785
BELOVED BY HIS TRAINEES. AND 

294
00:12:29,785 --> 00:12:31,320
PUBLISHED EXTENSIVELY. AND HAS 

295
00:12:31,320 --> 00:12:33,922
THREE CHILDREN. SO TO CELEBRATE 

296
00:12:33,922 --> 00:12:35,658
HIS LIFE, AND ALSO TO CELEBRATE 

297
00:12:35,658 --> 00:12:37,726
DIVERSITY IN GENERAL. 

298
00:12:37,726 --> 00:12:39,862
AND I HAVE LEARNED A LOT TODAY, 

299
00:12:39,862 --> 00:12:42,364
TALKING TO DR. OWENS, ABOUT THE 

300
00:12:42,364 --> 00:12:42,865
MISSION THAT HE AND HIS 

301
00:12:42,865 --> 00:12:49,071
ORGANIZATION AT NIH HAS.  SO, 

302
00:12:49,071 --> 00:12:50,806
TO REALLY REMEMBER THIS 

303
00:12:50,806 --> 00:12:51,740
WONDERFUL SCIENTISTS WHO WAS SO 

304
00:12:51,740 --> 00:12:52,574
PRODUCTIVE AND SO GIVING OF 

305
00:12:52,574 --> 00:12:56,178
HIMSELF. 

306
00:12:56,178 --> 00:12:57,446
WHAT I WOULD LIKE TO TALK ABOUT 

307
00:12:57,446 --> 00:13:03,218
TODAY IS REALLY CONCENTRATING 

308
00:13:03,218 --> 00:13:03,852
ON THE INNATE IMMUNE RECEPTORS 

309
00:13:03,852 --> 00:13:04,420
AND ON MY TALK A LITTLE BIT 

310
00:13:04,420 --> 00:13:10,192
ABOUT OUR OTHER WORK.  BUT 

311
00:13:10,192 --> 00:13:14,029
MAINLY FOCUS ON INNATE IMMUNE 

312
00:13:14,029 --> 00:13:14,630
RECEPTORS SOMETHING WE FOCUS 

313
00:13:14,630 --> 00:13:21,170
FOR OVER 24 YEARS. 

314
00:13:21,170 --> 00:13:21,704
WHEN WE LOOK AT THE INNATE 

315
00:13:21,704 --> 00:13:22,304
IMMUNE SYSTEM THERE ARE MANY 

316
00:13:22,304 --> 00:13:24,873
RECEPTORS THAT ARE ON THE CELL 

317
00:13:24,873 --> 00:13:33,248
SURFACE, MOST FAMOUS THE -- WE 

318
00:13:33,248 --> 00:13:35,284
THINK ABOUT RECEPTORS BEING ON 

319
00:13:35,284 --> 00:13:35,918
THE OUTSIDE FACING THE OUTSIDE 

320
00:13:35,918 --> 00:13:39,021
WORLD.  BUT IT TURNS OUT THAT 

321
00:13:39,021 --> 00:13:41,890
FOR CELLS, , JUST LIKE FOR US 

322
00:13:41,890 --> 00:13:42,524
RIGHT NOW THERE IS GREAT DANGER 

323
00:13:42,524 --> 00:13:46,095
ON THE OUTSIDE. BUT INSIDE 

324
00:13:46,095 --> 00:13:46,695
THERE IS ALSO A LOT OF DANGER 

325
00:13:46,695 --> 00:13:47,329
SO THE SYSTEM WITHIN THE CELL 

326
00:13:47,329 --> 00:13:53,769
HAS TO REALLY DETECT ALL OF 

327
00:13:53,769 --> 00:13:54,703
THESE DANGER SIGNALS, AS WE ALL 

328
00:13:54,703 --> 00:13:57,206
KNOW AT NIH. 

329
00:13:57,206 --> 00:14:07,649
WHAT I WOULD LIKE TO TELL YOU 

330
00:14:08,016 --> 00:14:08,550
IS OUR INTEREST IN THE INNATE 

331
00:14:08,550 --> 00:14:09,151
IMMUNE RECEPTOR STARTED FROM 

332
00:14:09,151 --> 00:14:11,687
HERE WHICH IS A FAMILY OF 

333
00:14:11,687 --> 00:14:12,321
PROTEINS  WHERE WE DID QUITE A 

334
00:14:12,321 --> 00:14:17,159
BIT OF WORK ON WHICH INCLUDES 

335
00:14:17,159 --> 00:14:18,794
-- AND I WILL TELL YOU ABOUT 

336
00:14:18,794 --> 00:14:19,395
DNA SENSORS, INCLUDE SOME OF 

337
00:14:19,395 --> 00:14:26,368
THE ONES HERE. AND I WILL TELL 

338
00:14:26,368 --> 00:14:26,969
YOU ABOUT THE BROAD IMPACT OF 

339
00:14:26,969 --> 00:14:27,603
THESE RECEPTORS I MANY DISEASES 

340
00:14:27,603 --> 00:14:30,072
SUCH AS IN CANCER, INFLAMMATORY 

341
00:14:30,072 --> 00:14:30,572
DISEASES AND INFECTIOUS 

342
00:14:30,572 --> 00:14:40,916
DISEASES OF COURSE. 

343
00:14:41,583 --> 00:14:42,117
SO OUR VENTURE INTO INNATE 

344
00:14:42,117 --> 00:14:42,618
IMMUNITY WAS COMPLETELY 

345
00:14:42,618 --> 00:14:43,218
UNEXPECTED; WE WERE INITIALLY 

346
00:14:43,218 --> 00:14:43,852
INTERESTED WHEN I WAS A POSTDOC 

347
00:14:43,852 --> 00:14:44,453
IN IMMUNE REGULATION AND THE 

348
00:14:44,453 --> 00:14:44,953
IMMUNE SYSTEM. 

349
00:14:44,953 --> 00:14:46,288
MARY CARRINGTON WHO IS HERE, I 

350
00:14:46,288 --> 00:14:49,158
THINK WERE A YEAR APART IN OUR 

351
00:14:49,158 --> 00:14:49,792
RESEARCH EXPERIENCE AND SHE WAS 

352
00:14:49,792 --> 00:14:54,396
SO NICE TO JOIN MY GROUP, WHICH 

353
00:14:54,396 --> 00:15:00,702
WAS NASCENT, NO PROMISE AT THAT 

354
00:15:00,702 --> 00:15:05,340
POINT.  WE LOOKED AT MHC GENE 

355
00:15:05,340 --> 00:15:12,948
RELATION WE LOOKED AT CIITA, 

356
00:15:12,948 --> 00:15:15,884
RESPONSIBLE FOR TRANSCRIPTION 

357
00:15:15,884 --> 00:15:21,590
OF CLASS GMH GENES. A 

358
00:15:21,590 --> 00:15:23,292
REMARKABLE PROTEIN BECAUSE AS I 

359
00:15:23,292 --> 00:15:25,294
MASTER A RELATION OF RMHC, 

360
00:15:25,294 --> 00:15:34,236
WHERE -- WHETHER CLASS II, ETC. 

361
00:15:34,236 --> 00:15:34,870
THIS IS REMARKABLE VOTING WHEN 

362
00:15:34,870 --> 00:15:39,274
YOU DO NOT HAVE CIITA, WHAT 

363
00:15:39,274 --> 00:15:49,418
HAPPENS?

364
00:16:10,138 --> 00:16:13,976
SO CIITA OVER HERE, AND LOSS OF 

365
00:16:13,976 --> 00:16:14,843
FUNCTION MUTATIONS IN CIITA, 

366
00:16:14,843 --> 00:16:17,946
BASED ON THE TYPE 2 BARE 

367
00:16:17,946 --> 00:16:20,048
LYMPHOCYTE SYNDROME, WHERE THE 

368
00:16:20,048 --> 00:16:26,321
PATIENT IS NOT EXPRESSED CLASS 

369
00:16:26,321 --> 00:16:34,463
2 -- AS A RESULT THESE PATIENTS 

370
00:16:34,463 --> 00:16:34,830
ARE VERY YEARLY 

371
00:16:34,830 --> 00:16:37,900
IMMUNODEFICIENCY.

372
00:16:37,900 --> 00:16:38,467
TWO PEOPLE IN MY LOVE DECIDED 

373
00:16:38,467 --> 00:16:39,568
TO SEE IF THERE WERE OTHER 

374
00:16:39,568 --> 00:16:43,305
GENES THAT LOOK LIKE CIITA, AND 

375
00:16:43,305 --> 00:16:43,939
THEY USED TWO DIFFERENT DOMAINS 

376
00:16:43,939 --> 00:16:47,709
IF THEY USE JUST ONE WITHOUT A 

377
00:16:47,709 --> 00:16:48,310
FOUND ASSEMBLY AND USING THE 

378
00:16:48,310 --> 00:16:49,044
NUCLEOTIDE BINDING DOMAIN CAME 

379
00:16:49,044 --> 00:16:50,312
UPON 22 GENES WITH DIFFERENT 

380
00:16:50,312 --> 00:16:55,384
END TERMINI, THAT WE EARLIER 

381
00:16:55,384 --> 00:16:56,018
CALLED CATERPILLAR, BECAUSE WE 

382
00:16:56,018 --> 00:16:58,453
WANTED TO BE VERY INCLUSIVE AND 

383
00:16:58,453 --> 00:16:59,021
INCLUDED ALL THE DOMAINS OF 

384
00:16:59,021 --> 00:16:59,521
THESE PROTEINS. 

385
00:16:59,521 --> 00:17:03,559
HOWEVER IT IS NOW KNOWN AS 

386
00:17:03,559 --> 00:17:10,666
NLRS, STANDING FOR NBD LR 

387
00:17:10,666 --> 00:17:12,868
PROTEINS ARE NOT RECEPTORS. 

388
00:17:12,868 --> 00:17:15,404
AND WHAT IS REMARKABLE IN THE 

389
00:17:15,404 --> 00:17:15,971
FAMILY, INITIALLY FOUND IN 

390
00:17:15,971 --> 00:17:18,774
PLANTS CALLED DISEASE 

391
00:17:18,774 --> 00:17:21,810
RESISTANCE GENES, AND SOME 

392
00:17:21,810 --> 00:17:22,411
PLANTS HAVE HUNDREDS OF THESE 

393
00:17:22,411 --> 00:17:23,011
GENES AND THEY ARE MOSTLY TO 

394
00:17:23,011 --> 00:17:25,080
DETECT CHANGES IN THE 

395
00:17:25,080 --> 00:17:25,714
ENVIRONMENT, AS WELL AS 

396
00:17:25,714 --> 00:17:29,518
PATHOGENIC CHANGES. 

397
00:17:29,518 --> 00:17:30,085
IN HUMANS, THERE ARE 22 SUCH 

398
00:17:30,085 --> 00:17:32,754
GENES.  THEY ALL HAVE WHAT IS 

399
00:17:32,754 --> 00:17:39,227
CALLED A NOC DOMAIN STANDING 

400
00:17:39,227 --> 00:17:39,861
FOR NUCLEOTIDE BINDING REGIONS 

401
00:17:39,861 --> 00:17:41,630
AS WELL AND  THEY REPEAT HERE 

402
00:17:41,630 --> 00:17:42,631
AND THEY HAVE DIFFERENT END 

403
00:17:42,631 --> 00:17:48,236
TERMINI.  THESE ARE THE 22 NLR 

404
00:17:48,236 --> 00:17:49,671
PROTEINS AND SOME HAVE MANY OF 

405
00:17:49,671 --> 00:17:53,175
THESE PROTEIN SUCH AS THE NRP, 

406
00:17:53,175 --> 00:17:55,444
THERE ARE AT LEAST 11-14 SUCH 

407
00:17:55,444 --> 00:17:57,913
PROTEINS. 

408
00:17:57,913 --> 00:18:03,018
MOST RECENTLY IT WAS FOUND THAT 

409
00:18:03,018 --> 00:18:03,585
PROKARYOTES SUCH AS E. COLI 

410
00:18:03,585 --> 00:18:07,456
ALSO HAVE THESE PROTEINS. AND 

411
00:18:07,456 --> 00:18:09,424
THESE ARE CALLED ANTIVIRAL 

412
00:18:09,424 --> 00:18:10,058
STRAND PROTEINS AND WHAT THEY 

413
00:18:10,058 --> 00:18:13,061
DO IS THEY HAVE A NUCLEASE THAT 

414
00:18:13,061 --> 00:18:17,699
CLEAVES VIRAL DNA, AND AS 

415
00:18:17,699 --> 00:18:18,600
RESULT CAN DEFEND E. COLI FOR 

416
00:18:18,600 --> 00:18:19,167
EXAMPLE AGAINST VIRUSES OF 

417
00:18:19,167 --> 00:18:20,836
BACTERIAL ORIGIN. 

418
00:18:20,836 --> 00:18:26,742
NOW,  JUST TO GIVE THIS SOME 

419
00:18:26,742 --> 00:18:27,409
PERSPECTIVE-- BECAUSE I KNOW 

420
00:18:27,409 --> 00:18:30,879
THIS IS A VERY BROAD AUDIENCE-- 

421
00:18:30,879 --> 00:18:31,346
THESE GENES ALSO BEEN 

422
00:18:31,346 --> 00:18:33,649
GENETICALLY LINKED TO DISEASES. 

423
00:18:33,649 --> 00:18:38,286
 AND I KNOW PAUL LU (PHONETIC) 

424
00:18:38,286 --> 00:18:39,254
HAS DONE A LOT OF WORK WITH 

425
00:18:39,254 --> 00:18:40,288
GENETICAL LINKAGE TO DISEASES 

426
00:18:40,288 --> 00:18:43,158
AND THE CIITA I ALREADY 

427
00:18:43,158 --> 00:18:43,825
MENTIONED IS LINKED TO TYPE II 

428
00:18:43,825 --> 00:18:48,530
BARE LYMPHOCYTE SYNDROME. AND 

429
00:18:48,530 --> 00:18:50,132
NOD2 IS ONE OF THE BEST GENETIC 

430
00:18:50,132 --> 00:18:55,170
DEFECTS IN CROHN'S DISEASE. AND 

431
00:18:55,170 --> 00:18:55,737
THIS PROTEIN WHICH IS WELL 

432
00:18:55,737 --> 00:18:56,371
KNOWN AT NIH AND I WILL GO INTO 

433
00:18:56,371 --> 00:18:59,675
THIS A BIT MORE CALLED 

434
00:18:59,675 --> 00:19:05,914
CRYOPYRIN OR NLPRP3 LINK TO 

435
00:19:05,914 --> 00:19:06,648
MULTIPLE AUTO INFLAMMATORY 

436
00:19:06,648 --> 00:19:08,750
DISEASES. 

437
00:19:08,750 --> 00:19:12,587
SO WHAT IS THIS FAMILY OF 

438
00:19:12,587 --> 00:19:15,290
DISEASES? THESE ALL GAIN A 

439
00:19:15,290 --> 00:19:21,063
FUNCTION MUTATION SO NLRP3 IS 

440
00:19:21,063 --> 00:19:21,663
IMPORTANT FOR INFORMATION BUT 

441
00:19:21,663 --> 00:19:23,699
WE HAVE A GANG FUNCTION 

442
00:19:23,699 --> 00:19:25,567
MUTATION WHICH LEADS TO SEVERE 

443
00:19:25,567 --> 00:19:26,201
PHYSIOLOGICAL DISEASES RELATED 

444
00:19:26,201 --> 00:19:31,373
TO AN INCREASE IL-1 DENSITIES 

445
00:19:31,373 --> 00:19:36,211
WHICH I WILL GET INTO A LITTLE 

446
00:19:36,211 --> 00:19:36,812
MORE.  THE TREATMENT IS IL-1 

447
00:19:36,812 --> 00:19:38,780
RECEPTOR ANTAGONIST OR 

448
00:19:38,780 --> 00:19:41,983
ANTIBODIES AGAINST IL-1.  

449
00:19:41,983 --> 00:19:42,517
AND INITIALLY THIS WAS THE 

450
00:19:42,517 --> 00:19:43,151
DISCOVERY OF A YOUNG FACULTY AT 

451
00:19:43,151 --> 00:19:45,754
THE TIME, NOT TO SAY THAT HE IS 

452
00:19:45,754 --> 00:19:46,588
OLD-- BUT IT'S BEEN QUITE A FEW 

453
00:19:46,588 --> 00:19:53,962
YEARS NOW-- HAL HOFFMAN AT UCSD 

454
00:19:53,962 --> 00:19:55,597
AND DAN AND HIS COLLEAGUE THE 

455
00:19:55,597 --> 00:20:01,169
TELEWORK -- AND -- DID A LOT OF 

456
00:20:01,169 --> 00:20:02,971
WORK ON THIS DISEASE FAMILY 

457
00:20:02,971 --> 00:20:03,505
INCLUDING IS MORE SEVERE 

458
00:20:03,505 --> 00:20:11,546
VERSIONS CALLED NOMID OR SYNCA 

459
00:20:11,546 --> 00:20:13,381
(PHONETIC). THESE ANTIBODIES 

460
00:20:13,381 --> 00:20:15,417
ARE IL-1 ANTAGONIST THAT WILL 

461
00:20:15,417 --> 00:20:18,553
TARGET IL-1.  PATIENTS REALLY 

462
00:20:18,553 --> 00:20:22,991
GET BETTER WITHIN DAYS WHICH IS 

463
00:20:22,991 --> 00:20:23,592
REMARKABLE. BEFORE THEY WOULD 

464
00:20:23,592 --> 00:20:24,159
HAVE FLASHES-- IN THE LESS 

465
00:20:24,159 --> 00:20:27,829
SEVERE CASES TO REALLY CNS 

466
00:20:27,829 --> 00:20:29,364
PROBLEMS AS WELL AS SEVERE 

467
00:20:29,364 --> 00:20:30,899
INFORMATION,  IN THIS CASE OF 

468
00:20:30,899 --> 00:20:33,969
THE KNEES. 

469
00:20:33,969 --> 00:20:34,503
SO THERE ARE MANY MUTATIONS 

470
00:20:34,503 --> 00:20:40,876
THAT HAVE BEEN FOUND IN THIS 

471
00:20:40,876 --> 00:20:41,476
DISEASE. ALL OF THESE CAN BE 

472
00:20:41,476 --> 00:20:42,110
TREATED BY THESE ANTIBODIES AND 

473
00:20:42,110 --> 00:20:44,246
THIS THE TRIUMPH OF TRANSLATING 

474
00:20:44,246 --> 00:20:46,148
THE BENCH TO BEDSIDE. AND MUCH 

475
00:20:46,148 --> 00:20:46,782
OF THIS WORK IS REALLY DONE AT 

476
00:20:46,782 --> 00:20:50,318
NIH. 

477
00:20:50,318 --> 00:20:55,257
SO, IT TURNS OUT THESE NLRS 

478
00:20:55,257 --> 00:21:01,763
PROTEINS WHAT THEY DO IS THEY 

479
00:21:01,763 --> 00:21:06,501
FORM THE MULTIMERS CALLED THE 

480
00:21:06,501 --> 00:21:08,136
-- RECEPTOR FOR DIFFERENT 

481
00:21:08,136 --> 00:21:12,073
LIGANDS INDICATED HERE AND WHAT 

482
00:21:12,073 --> 00:21:13,341
THEY DO IS THE ACTIVITY IN SOME 

483
00:21:13,341 --> 00:21:13,942
CASES WE STILL DON'T KNOW HOW 

484
00:21:13,942 --> 00:21:18,980
THIS IS DONE. BUT THE ACTIVATE 

485
00:21:18,980 --> 00:21:22,651
THE INFLAMA ZONE RECEPTOR, THIS 

486
00:21:22,651 --> 00:21:30,258
RECRUITS PRO CAS BASE 1 ENZYE, 

487
00:21:30,258 --> 00:21:40,802
WHICH  ACTIVATESPRO-CASPASE 1. 

488
00:21:45,740 --> 00:21:50,178
AND THIS IS THE INFLAMMAZONE. 

489
00:21:50,178 --> 00:21:55,650
SO, ONE IMPORTANT CONCEPT IN IN 

490
00:21:55,650 --> 00:22:02,490
THE INFLAMMAZONE, IS IT 

491
00:22:02,490 --> 00:22:03,491
REQUIRES TWO STEPS. THE FIRST 

492
00:22:03,491 --> 00:22:06,027
THAT IS LEADING ACTIVATION TO 

493
00:22:06,027 --> 00:22:07,596
INFLAMMAZONE COMPONENTS FOR 

494
00:22:07,596 --> 00:22:18,139
EXAMPLE TLR CAN  PRIME THIS AND 

495
00:22:19,875 --> 00:22:20,442
TLF CAN PRIME THIS MEETING THE 

496
00:22:20,442 --> 00:22:22,844
DESCRIPTION OF MANY 

497
00:22:22,844 --> 00:22:26,314
INFLAMMAZONE COMPONENTS. 

498
00:22:26,314 --> 00:22:26,915
AND THESE PROTEINS ARE FROM AND 

499
00:22:26,915 --> 00:22:30,886
THEY GO THROUGH 

500
00:22:30,886 --> 00:22:31,519
POST-TRANSLATIONAL  ALLOCATION 

501
00:22:31,519 --> 00:22:32,153
THAT IS STILL THE PRIMING PHASE 

502
00:22:32,153 --> 00:22:37,058
SUCH AS PHOSPHORYLATION, ETC. 

503
00:22:37,058 --> 00:22:37,792
ALL OF THESE COMPONENTS ARE 

504
00:22:37,792 --> 00:22:38,393
READY TO BE ASSEMBLED IN THE 

505
00:22:38,393 --> 00:22:40,161
SECOND STEP IS SIGNAL 2, 

506
00:22:40,161 --> 00:22:40,829
ACTIVATION CAUSING THE ASSEMBLY 

507
00:22:40,829 --> 00:22:44,232
OF THESE INFLAMMAZONE DIFFERENT 

508
00:22:44,232 --> 00:22:44,833
COMPONENTS INTO THIS LARGE 

509
00:22:44,833 --> 00:22:47,502
COMPLEX. 

510
00:22:47,502 --> 00:22:49,804
AND SO THIS THEN CAUSES IL-1 

511
00:22:49,804 --> 00:22:54,643
SECRETION IN IO-8 AND I ALSO 

512
00:22:54,643 --> 00:23:01,549
MENTIONED GASTRIN B, WHICH 

513
00:23:01,549 --> 00:23:02,183
CLEAVED AND FORMS THE MEMBRANE 

514
00:23:02,183 --> 00:23:04,986
AND NOW WE HAVE THE MATURE FORM 

515
00:23:04,986 --> 00:23:06,988
RESULTING IN INFLAMMATION AND 

516
00:23:06,988 --> 00:23:07,589
IN CELL DEATH. THESE ARE TWO 

517
00:23:07,589 --> 00:23:08,189
DIFFERENT COMPONENTS OF THE 

518
00:23:08,189 --> 00:23:13,561
INFLAMMAZONE. 

519
00:23:13,561 --> 00:23:16,331
THIS FIELD HAS TO LOOK AT TONS 

520
00:23:16,331 --> 00:23:20,268
OF FUNCTIONS OF INFLAMMAZONE.  

521
00:23:20,268 --> 00:23:20,869
ALL OF THESE THAT I MENTIONED 

522
00:23:20,869 --> 00:23:22,304
HAVE ALSO BEEN DONE AT THE SAME 

523
00:23:22,304 --> 00:23:22,938
TIME, OR MAYBE A LITTLE BIT 

524
00:23:22,938 --> 00:23:28,209
LATER, BY OTHERS IN THE FIELD.  

525
00:23:28,209 --> 00:23:28,843
SOMETIMES A LITTLE BIT EARLIER 

526
00:23:28,843 --> 00:23:29,411
BY OTHERS IN THE FIELD FOR 

527
00:23:29,411 --> 00:23:33,715
EXAMPLE WE FOUND THAT 

528
00:23:33,715 --> 00:23:34,349
INFLAMMAZONE IS VERY IMPORTANT 

529
00:23:34,349 --> 00:23:34,849
FOR INFLUENZA AND ALSO 

530
00:23:34,849 --> 00:23:36,251
IMPORTANT FOR AUTOIMMUNE 

531
00:23:36,251 --> 00:23:38,687
DISEASES THAT ARE T CELL 

532
00:23:38,687 --> 00:23:43,258
MEDIATED SUCH AS EAE AND MODEL 

533
00:23:43,258 --> 00:23:45,760
FOR MULTIPLE SCLEROSIS,  IS 

534
00:23:45,760 --> 00:23:46,261
IMPORTANT FOR METABOLIC 

535
00:23:46,261 --> 00:23:46,861
DISEASES AND OUR PAPER SHOWED 

536
00:23:46,861 --> 00:23:47,429
IT IS REALLY ACTIVATED BY 

537
00:23:47,429 --> 00:23:48,863
SATURATED FATTY ACID.  THIS IS 

538
00:23:48,863 --> 00:23:52,634
ONE WORK DONE BY -- NOW 

539
00:23:52,634 --> 00:23:55,570
PROFESSOR AT OHIO STATE. 

540
00:23:55,570 --> 00:23:58,273
AND THEN WE HAVE PAPERS 

541
00:23:58,273 --> 00:24:00,909
INDICATING ITS IMPORTANCE IN 

542
00:24:00,909 --> 00:24:01,443
NEURONAL INFORMATION AND 

543
00:24:01,443 --> 00:24:02,911
INFORMATION THAT DOES NOT 

544
00:24:02,911 --> 00:24:06,648
REQUIRE T CELLS. 

545
00:24:06,648 --> 00:24:07,248
IN ADDITION WE FOUND THAT THESE 

546
00:24:07,248 --> 00:24:07,749
ARE REALLY IMPORTANT IN 

547
00:24:07,749 --> 00:24:10,518
COLITIS, COLON CANCER, ETC. 

548
00:24:10,518 --> 00:24:12,320
THE BROAD IMPACT OF 

549
00:24:12,320 --> 00:24:13,655
INFLAMMAZONE IS IN MANY 

550
00:24:13,655 --> 00:24:18,393
DISEASES.  FOR THIS REASON 

551
00:24:18,393 --> 00:24:19,361
THERE ARE BILLIONS OF DOLLARS 

552
00:24:19,361 --> 00:24:19,928
SPENT BY PHARMA LOOKING AT 

553
00:24:19,928 --> 00:24:22,430
INHIBITORS OF THIS PATHWAY.  

554
00:24:22,430 --> 00:24:22,964
MANY OF THEM ARE LOOKING 

555
00:24:22,964 --> 00:24:24,933
PROMISING. 

556
00:24:24,933 --> 00:24:30,805
SO, WHEN THE COVID CRISIS 

557
00:24:30,805 --> 00:24:31,439
STARTED, WE LIKE EVERYBODY ELSE 

558
00:24:31,439 --> 00:24:32,407
HAD TO CLOSE DOWN OUR LAB. ONE 

559
00:24:32,407 --> 00:24:34,042
OF THE POSTDOCS IN MY LAB 

560
00:24:34,042 --> 00:24:36,378
REALLY WANTED TO STUDY COVID.  

561
00:24:36,378 --> 00:24:36,978
AND ASSET WE HAVE NEVER DONE 

562
00:24:36,978 --> 00:24:42,384
THIS.  WE HAVE TO WORK ON BSL 3 

563
00:24:42,384 --> 00:24:47,222
FACILITIES, ETC. THE CAP WAS 

564
00:24:47,222 --> 00:24:47,822
UNDAUNTED. SHE WANTED TO TAKE 

565
00:24:47,822 --> 00:24:49,858
THE ROLES OF INFLAMMAZONES ON 

566
00:24:49,858 --> 00:24:51,826
COVID.  THERE WERE INDICATIONS 

567
00:24:51,826 --> 00:24:53,962
THAT AN AND SEVERE COVID 

568
00:24:53,962 --> 00:24:55,497
PATIENTS THERE WAS AN INCREASE 

569
00:24:55,497 --> 00:25:00,335
IN IL-1 AND IL-6, AND IN 

570
00:25:00,335 --> 00:25:00,869
CHILDREN ONE OF THE MAIN 

571
00:25:00,869 --> 00:25:03,405
OUTCOMES IS INCREASES IN IL-1. 

572
00:25:03,405 --> 00:25:07,776
IN LONG COVID THERE IS SEQUELAE 

573
00:25:07,776 --> 00:25:11,046
OF IL-1. 

574
00:25:11,046 --> 00:25:15,316
AND IN SEVERE COVID PATIENTS, 

575
00:25:15,316 --> 00:25:16,718
THE RESULTS ARE MIXED. THERE 

576
00:25:16,718 --> 00:25:17,552
ARE A FEW GOOD PAPERS LOOKING 

577
00:25:17,552 --> 00:25:22,690
AT IL-1 INHIBITORS IN SEVERE 

578
00:25:22,690 --> 00:25:23,158
COVID WHERE THERE ARE 

579
00:25:23,158 --> 00:25:23,625
INDICATORS OF STRONG 

580
00:25:23,625 --> 00:25:27,262
INFLAMMATORY COMPONENT SUCH AS 

581
00:25:27,262 --> 00:25:30,932
NOT ONLY INFLAMMATORY CYTOKINES 

582
00:25:30,932 --> 00:25:31,566
ALSO IN QUAD RELATION PROBLEMS 

583
00:25:31,566 --> 00:25:36,037
AND THAT IS WHERE IL-1 SEEMS TO 

584
00:25:36,037 --> 00:25:36,671
BE USEFUL SO SHE WAS INTERESTED 

585
00:25:36,671 --> 00:25:39,541
IN LOOKING AT THIS AND MANY OF 

586
00:25:39,541 --> 00:25:41,543
THE STUDIES WERE DONE AFTER WE 

587
00:25:41,543 --> 00:25:43,411
STARTED OUR PROJECTS. 

588
00:25:43,411 --> 00:25:46,581
WHAT CAT WAS LOOKING AT WAS THE 

589
00:25:46,581 --> 00:25:50,118
SYSTEM, THE FIRST STEP OF 

590
00:25:50,118 --> 00:25:51,052
COVID, THE INFECTION OF THE 

591
00:25:51,052 --> 00:26:01,396
PRIMARY AIRWAY EPITHELIAL 

592
00:26:01,396 --> 00:26:06,968
CELLS. AND SCOTT -- INVENTED 

593
00:26:06,968 --> 00:26:07,569
THIS WHOLE SYSTEM TO LOOK AT 

594
00:26:07,569 --> 00:26:09,637
OTHER DISEASES IN THE CNS. 

595
00:26:09,637 --> 00:26:11,439
AND THIS IS A CHEAT SHEET, IN 

596
00:26:11,439 --> 00:26:12,006
CASE YOU WANTED TO LOOK AT 

597
00:26:12,006 --> 00:26:15,076
SIGNALS 1 AND 2.  THERE ARE 

598
00:26:15,076 --> 00:26:15,610
DIFFERENT THINGS THAT ARE 

599
00:26:15,610 --> 00:26:16,878
ACTIVATED IN INFLAMMAZONE IN 

600
00:26:16,878 --> 00:26:23,051
SIGNAL 1 AND SIGNAL 2. 

601
00:26:23,051 --> 00:26:23,585
 WHAT WE HAVE FOUND IN THIS 

602
00:26:23,585 --> 00:26:24,152
WHOLE SYSTEM IS THAT AIRWAY 

603
00:26:24,152 --> 00:26:26,521
EPITHELIAL CELLS CAN MAKE IL-1, 

604
00:26:26,521 --> 00:26:27,355
WHEN THEY ARE RESPONDED AND 

605
00:26:27,355 --> 00:26:28,857
INDUCED A PROPERTY BY SIGNAL 1 

606
00:26:28,857 --> 00:26:31,359
AND SIGNAL 2. 

607
00:26:31,359 --> 00:26:40,034
IN THIS CASE PAM3 IS SIGNAL 1 

608
00:26:40,034 --> 00:26:48,443
AND VAL-BOROPRO WAS SIGNAL 2. 

609
00:26:48,443 --> 00:26:49,043
THIS WAS THE FIRST INDICATION 

610
00:26:49,043 --> 00:26:50,979
THAT THE CELL TYPE CAN SECRETE 

611
00:26:50,979 --> 00:26:51,880
IL-1. 

612
00:26:51,880 --> 00:26:58,486
WE WONDERED IF COVID  COULD 

613
00:26:58,486 --> 00:26:59,020
PARTICIPATE IN THIS SO WE 

614
00:26:59,020 --> 00:27:00,255
LOOKED AT SARS COVID-2 

615
00:27:00,255 --> 00:27:02,190
EPITHELIAL CELLS. I REMEMBER 

616
00:27:02,190 --> 00:27:04,826
THIS IS THE FACE OF PFU AND WE 

617
00:27:04,826 --> 00:27:11,366
SAW THAT SARS-COVID-2 

618
00:27:11,366 --> 00:27:13,201
INFECTIONS WERE ABLE TO 

619
00:27:13,201 --> 00:27:14,369
DUPLICATE AN INCREASE IN THE 

620
00:27:14,369 --> 00:27:15,003
CELL CULTURES. HOWEVER WE 

621
00:27:15,003 --> 00:27:19,774
LOOKED AT IL-1, WE SAW THAT 

622
00:27:19,774 --> 00:27:24,345
SARS-COVID-2 CANNOT INDUCE ANY 

623
00:27:24,345 --> 00:27:24,946
IL-1 IN THIS EPITHELIAL CELLS 

624
00:27:24,946 --> 00:27:27,415
AND THESE ARE THE ONES 

625
00:27:27,415 --> 00:27:33,588
EXPRESSING ALL THE RECEPTORS OF 

626
00:27:33,588 --> 00:27:34,222
SARS-COVID-2. THIS IS SIMPLY A 

627
00:27:34,222 --> 00:27:36,491
PROCESS CONTROL. 

628
00:27:36,491 --> 00:27:40,395
SO THEN WE MOVED ON.  WE WANTED 

629
00:27:40,395 --> 00:27:42,463
TO SEE WHAT IS THE EFFECT OF 

630
00:27:42,463 --> 00:27:46,968
SARS COVID 2 ON HUMANS. THERE 

631
00:27:46,968 --> 00:27:47,602
WERE QUITE A FEW PAPERS LOOKING 

632
00:27:47,602 --> 00:27:48,236
AT THE INDUCTION OF 

633
00:27:48,236 --> 00:27:58,780
INFLAMMAZONE BY S ARS-COVID-2. 

634
00:27:59,047 --> 00:27:59,581
SOME REQUIRED PRIMING SIGNALS 

635
00:27:59,581 --> 00:28:05,587
AND SOME ANTIBODIES. NOBODY WAS 

636
00:28:05,587 --> 00:28:06,120
LOOKING AT JUST THE VIRUS 

637
00:28:06,120 --> 00:28:07,488
ITSELF. WE WANTED TO LOOK AT 

638
00:28:07,488 --> 00:28:09,057
THE VIRUS ITSELF AND WHAT IT 

639
00:28:09,057 --> 00:28:13,228
DID TO PBMC. 

640
00:28:13,228 --> 00:28:13,828
THE VIRUS TO GET IN BUT DO NOT 

641
00:28:13,828 --> 00:28:16,197
SEEM TO REPLICATE ACTIVELY. THE 

642
00:28:16,197 --> 00:28:19,701
VIRUS VERY QUICKLY GOES DOWN IN 

643
00:28:19,701 --> 00:28:22,837
PFUS. 

644
00:28:22,837 --> 00:28:23,671
IF WE LOOK AT EXPRESSION, WE 

645
00:28:23,671 --> 00:28:24,539
SAW THE SAME. THIS IS THE 

646
00:28:24,539 --> 00:28:29,711
EXPRESSION OF THE END PROTEIN 

647
00:28:29,711 --> 00:28:32,714
OF SARS-COV2,  AND THE VIRUSES 

648
00:28:32,714 --> 00:28:43,258
NOT ACTIVELY REPLICATE ON THESE 

649
00:28:47,095 --> 00:28:47,595
PBMCS. WE NOTICE THAT WHEN 

650
00:28:47,595 --> 00:28:48,263
LOOKED AT IL-1 THERE IS NO IL-1 

651
00:28:48,263 --> 00:28:53,635
PRODUCTION. 

652
00:28:53,635 --> 00:28:56,471
SO SARS-COV2 WHEN THE 

653
00:28:56,471 --> 00:29:06,948
DISINFECTING PBMC DOES NOT 

654
00:29:10,184 --> 00:29:11,853
INDUCE INFLAMMAZONE.

655
00:29:11,853 --> 00:29:12,820
WHAT WE NOTICE THIS WHEN WE 

656
00:29:12,820 --> 00:29:17,925
LOOK AT SARS-COV2 BY ITSELF 

657
00:29:17,925 --> 00:29:19,861
INDICATED HERE, IT REDUCED 

658
00:29:19,861 --> 00:29:27,368
RELATIVE EXPRESSION OF THE 

659
00:29:27,368 --> 00:29:31,472
INFLAMMAZONE RNA. ALL WERE 

660
00:29:31,472 --> 00:29:41,683
INDUCED BY SARS-COV2 NICELY. 

661
00:29:41,683 --> 00:29:42,350
WE LOOK AT THE ABILITY TO 

662
00:29:42,350 --> 00:29:44,652
REDUCE THE INFLAMMAZONE, THIS 

663
00:29:44,652 --> 00:29:51,959
IS IL-1, -- WE HAVE SARS-COV2 

664
00:29:51,959 --> 00:29:52,593
RIGHT HERE IN THE BLUE OUTLINE 

665
00:29:52,593 --> 00:29:55,163
AREA THERE IS NO IL-1. 

666
00:29:55,163 --> 00:29:55,863
WHAT IS REQUIRED TO CAUSE 

667
00:29:55,863 --> 00:30:03,271
SARS-COV2 TO INDUCE IL-1? HERE 

668
00:30:03,271 --> 00:30:04,672
IT IS BY ITSELF AND THEN WE 

669
00:30:04,672 --> 00:30:09,277
ADDED SIGNAL TO ATP, AND 

670
00:30:09,277 --> 00:30:11,279
FINALLY WE ARE GETTING IL-1 

671
00:30:11,279 --> 00:30:11,913
PRODUCE AND THIS IS VERY 

672
00:30:11,913 --> 00:30:20,822
RESPECTABLE IL-1, ABOUT 

673
00:30:20,822 --> 00:30:22,223
1000-2000 PICOGRAMS PER MIL. 

674
00:30:22,223 --> 00:30:24,692
CAN ONLY BE SIGNAL 1, NOT 

675
00:30:24,692 --> 00:30:27,195
SIGNAL 2. 

676
00:30:27,195 --> 00:30:27,762
IT PROVIDED THE MECHANISM OF 

677
00:30:27,762 --> 00:30:28,396
HOW THIS IS DONE AND SARS-COV2 

678
00:30:28,396 --> 00:30:36,237
IS JUST SIGNAL 1 IN PBMCS. 

679
00:30:36,237 --> 00:30:36,838
WHAT IS THE PATTERN RECOGNITION 

680
00:30:36,838 --> 00:30:45,146
MOLECULE CAUSES SARS-COV2 TO BE 

681
00:30:45,146 --> 00:30:49,417
SIGNAL 1?

682
00:30:49,417 --> 00:30:49,984
WE DETECTED THIS ONE WHICH IS 

683
00:30:49,984 --> 00:30:51,652
THE ENVELOPE PROTEIN, THE E 

684
00:30:51,652 --> 00:30:59,761
PROTEIN. THIS TURNS OUT TO BE A 

685
00:30:59,761 --> 00:31:02,296
SIGNAL TO INDUCE IL-1 

686
00:31:02,296 --> 00:31:04,866
TRANSCRIPTION AND THIS IS E 

687
00:31:04,866 --> 00:31:06,033
PROTEIN AND LOOKING AT THE 

688
00:31:06,033 --> 00:31:09,303
FIRST STEP OF INFLAMMAZONE 

689
00:31:09,303 --> 00:31:12,940
INDUCTION WHICH IS IL-1 

690
00:31:12,940 --> 00:31:20,415
MESSAGE, MRNA PRODUCTION. AND 

691
00:31:20,415 --> 00:31:22,283
THE E PROTEIN WAS ABLE TO 

692
00:31:22,283 --> 00:31:24,819
INDUCE MRNA PRODUCTION 

693
00:31:24,819 --> 00:31:28,322
SUFFICIENT TO CAUSE IL-1 

694
00:31:28,322 --> 00:31:28,923
PROTEIN PRODUCTION AND INDEED 

695
00:31:28,923 --> 00:31:31,259
THAT IS WHAT WE SAW SO WE USE E 

696
00:31:31,259 --> 00:31:33,428
PROTEIN AND S PROTEIN AS A 

697
00:31:33,428 --> 00:31:35,329
NEGATIVE CONTROL. WE INCLUDE A 

698
00:31:35,329 --> 00:31:39,400
SIGNAL 2, WHICH IS ATP. AND WE 

699
00:31:39,400 --> 00:31:42,203
WERE ABLE TO SEE THAT THIS NOW 

700
00:31:42,203 --> 00:31:45,807
INDUCED SIGNIFICANT IL-1. 

701
00:31:45,807 --> 00:31:48,943
IN PBMCS, E PROTEIN IS ONE THAT 

702
00:31:48,943 --> 00:31:52,280
ACCESS SIGNAL 1 IN INFLAMMAZONE 

703
00:31:52,280 --> 00:31:55,383
ACTIVATION. SO WE WERE ABLE TO 

704
00:31:55,383 --> 00:31:56,017
IDENTIFY THE SPECIFIC MOLECULE 

705
00:31:56,017 --> 00:32:00,922
INVOLVED. 

706
00:32:00,922 --> 00:32:04,192
SO, THEN WE WANTED TO KNOW WE 

707
00:32:04,192 --> 00:32:07,128
HAVE IN AN INFECTED LUNG, YOU 

708
00:32:07,128 --> 00:32:13,901
HAVE THE LONG CELLS, AND THE 

709
00:32:13,901 --> 00:32:15,236
EPITHELIAL DEAL CELLS ARE ONE 

710
00:32:15,236 --> 00:32:18,973
OF THE COMPONENTS. THE SECOND 

711
00:32:18,973 --> 00:32:19,574
COMPONENT WILL BE THE IMMUNE 

712
00:32:19,574 --> 00:32:20,341
CELLS AND MANY OF THESE WOULD 

713
00:32:20,341 --> 00:32:26,414
BE PBMCS.  THIS IS VERY HARD TO 

714
00:32:26,414 --> 00:32:27,248
DO WITH THE HUMAN AIRWAY 

715
00:32:27,248 --> 00:32:34,322
EPITHELIAL CELLS SO WE USED -- 

716
00:32:34,322 --> 00:32:34,822
CELLS, A GOOD SOURCE OF 

717
00:32:34,822 --> 00:32:36,858
INFECTION BY SARS-COV2. WE 

718
00:32:36,858 --> 00:32:38,726
INFECTED THESE WITH SARS-COV2, 

719
00:32:38,726 --> 00:32:40,595
AND NOTHING HAPPENS WITH IL-1 

720
00:32:40,595 --> 00:32:43,798
AS I INDICATED.  SO IT WE JUST 

721
00:32:43,798 --> 00:32:44,632
HAVE THESE CELLS SEPARATELY 

722
00:32:44,632 --> 00:32:45,666
THEY CANNOT PRODUCE IL-1, EVEN 

723
00:32:45,666 --> 00:32:48,836
THOUGH SARS-COV2 IN PBMC CAN 

724
00:32:48,836 --> 00:32:52,640
ACT AS SIGNAL 1. 

725
00:32:52,640 --> 00:32:53,140
WHEN WE CULTURE THESE TWO 

726
00:32:53,140 --> 00:32:54,675
TOGETHER, HOWEVER, ALL OF A 

727
00:32:54,675 --> 00:32:57,478
SUDDEN WE ARE SEEING VERY 

728
00:32:57,478 --> 00:33:02,216
RESPECTABLE IL-1.  WE WERE ABLE 

729
00:33:02,216 --> 00:33:02,750
TO PUT THE TWO TOGETHER, 

730
00:33:02,750 --> 00:33:03,217
SUGGESTING THAT SOME 

731
00:33:03,217 --> 00:33:03,851
INTERACTION HAS TO HAPPEN 

732
00:33:03,851 --> 00:33:07,088
BETWEEN PBMC AND THE EPITHELIAL 

733
00:33:07,088 --> 00:33:09,590
CELLS TO GET SIGNAL 1. 

734
00:33:09,590 --> 00:33:11,125
WE WERE ABLE TO SHOW THAT THIS 

735
00:33:11,125 --> 00:33:14,729
IS CASPASE 1 INDEPENDENT 

736
00:33:14,729 --> 00:33:17,331
BECAUSE WE USE THE CASPASE 1 

737
00:33:17,331 --> 00:33:18,366
INHIBITOR AND I WOULD GET 

738
00:33:18,366 --> 00:33:19,534
NOTHING, NOT SO MUCH DEPENDING 

739
00:33:19,534 --> 00:33:24,171
ON NRP 3 BECAUSE WE ADDED THE 

740
00:33:24,171 --> 00:33:25,940
INHIBITOR, AND ONLY REDUCE BY 

741
00:33:25,940 --> 00:33:26,507
ABOUT 40%. SO THERE IS 

742
00:33:26,507 --> 00:33:31,312
SOMETHING ASIDE FROM NRP 3 WE 

743
00:33:31,312 --> 00:33:34,382
ARE WORKING ON THAT RIGHT NOW 

744
00:33:34,382 --> 00:33:35,016
AND WE HAVE SOME INDICATION BUT 

745
00:33:35,016 --> 00:33:35,650
IT IS NOT QUITE READY FOR PRIME 

746
00:33:35,650 --> 00:33:37,685
TIME. SO REALLY TWO DIFFERENT 

747
00:33:37,685 --> 00:33:38,586
CELL CULTURES HAVE TO COME 

748
00:33:38,586 --> 00:33:41,322
TOGETHER TO GET IL-1. 

749
00:33:41,322 --> 00:33:42,757
SO, WE WANTED TO KNOW WHAT IS 

750
00:33:42,757 --> 00:33:50,331
IT IN SARS-COV2-INFECTED AIRWAY 

751
00:33:50,331 --> 00:33:50,898
EPITHELIAL CELLS IN HUMANS 

752
00:33:50,898 --> 00:33:53,334
ACTING AS SIGNAL 2? WHAT WE 

753
00:33:53,334 --> 00:33:54,569
FOUND IS WE LOOKED JUST AT THE 

754
00:33:54,569 --> 00:33:59,640
CULTURE -- OF THESE INFECTED 

755
00:33:59,640 --> 00:34:00,241
AIRWAYS EPITHELIAL CELLS AND 

756
00:34:00,241 --> 00:34:01,976
WERE ABLE TO FIND THAT 

757
00:34:01,976 --> 00:34:05,580
SARS-COV2 RELEASES GERMLINE 

758
00:34:05,580 --> 00:34:08,549
DNA, ALSO MITOCHONDRIAL DNA AND 

759
00:34:08,549 --> 00:34:14,522
WE CAN PCR OUT SPECIFIC 

760
00:34:14,522 --> 00:34:15,289
MITOCHONDRIAL DNA. THESE CELLS 

761
00:34:15,289 --> 00:34:17,858
ARE DYING AND RELEASING DNA 

762
00:34:17,858 --> 00:34:19,827
FROM THE CELLS. AND WE KNOW 

763
00:34:19,827 --> 00:34:25,499
THAT DNA CAN BE A SIGNAL 2. 

764
00:34:25,499 --> 00:34:27,535
WHAT WE DID IS AGAIN TOOK VIRAL 

765
00:34:27,535 --> 00:34:28,135
CELLS AS A REPRESENTATIVE OF 

766
00:34:28,135 --> 00:34:31,505
AIRWAY CELLS AND ADDED PBMC. 

767
00:34:31,505 --> 00:34:34,442
THE TWO TOGETHER RELEASED IL-1, 

768
00:34:34,442 --> 00:34:35,009
THAT IS BECAUSE VIRAL CELLS 

769
00:34:35,009 --> 00:34:38,212
PRODUCE SIGNAL 2, PBMC PROVIDE 

770
00:34:38,212 --> 00:34:40,581
SIGNAL 1. I WANTED TO KNOW IF 

771
00:34:40,581 --> 00:34:45,252
THE SIGNAL 2 IS DNA. WE TREATED 

772
00:34:45,252 --> 00:34:46,554
THE CROSS CULTURE WITH DNA AND 

773
00:34:46,554 --> 00:34:50,958
SIGNAL 1 WENT WAY DOWN. AND 

774
00:34:50,958 --> 00:34:51,559
THEY SUGGEST THAT VIRAL CELLS 

775
00:34:51,559 --> 00:34:54,295
CAN RELEASE DNA AND WHEN YOU 

776
00:34:54,295 --> 00:34:56,998
GET RID OF THE DNA, SIGNAL 2  

777
00:34:56,998 --> 00:34:57,865
IS GREATLY REDUCED AND NOW WE 

778
00:34:57,865 --> 00:35:02,403
HAVE REDUCED IL-1 EXPRESSION. 

779
00:35:02,403 --> 00:35:04,538
WITHIN WANTED TO KNOW IF THIS 

780
00:35:04,538 --> 00:35:08,242
REALLY HAPPENS IN PATIENTS. AND 

781
00:35:08,242 --> 00:35:08,676
WE DID ALL SORTS OF 

782
00:35:08,676 --> 00:35:09,276
COMPUTATIONAL BIOLOGY THAT I 

783
00:35:09,276 --> 00:35:09,944
WON'T BE SHOWING YOU. WE SAW AN 

784
00:35:09,944 --> 00:35:13,180
INCREASE OF IL-1 IN SEVERE 

785
00:35:13,180 --> 00:35:15,216
COVID PATIENTS AND WE SEE 

786
00:35:15,216 --> 00:35:16,117
COMPONENTS OF IL-1 INCREASE, 

787
00:35:16,117 --> 00:35:22,757
AND WE SAW CERTAIN NLR PROTEINS 

788
00:35:22,757 --> 00:35:24,659
INCREASE. I WANT TO KNOW IN 

789
00:35:24,659 --> 00:35:27,261
PATIENTS, OUR CONTROL, A 

790
00:35:27,261 --> 00:35:28,663
HEALTHY CONTROLS BUT HAVE A 

791
00:35:28,663 --> 00:35:29,764
HEALTHY LUNG DISEASE VERSUS 

792
00:35:29,764 --> 00:35:34,602
COVID 19 INFECTED PATIENTS AND 

793
00:35:34,602 --> 00:35:38,239
THEIR LUNGS. DO WE SEE 

794
00:35:38,239 --> 00:35:40,608
DIFFERENCES IN THE AMOUNT OF 

795
00:35:40,608 --> 00:35:42,643
INFLAMMAZONE? WE INDEED SAW 

796
00:35:42,643 --> 00:35:43,244
THAT AND BY DOING THAT  A WE 

797
00:35:43,244 --> 00:35:53,788
LOOK FORC ASC SPECK FORMATION. 

798
00:35:57,925 --> 00:35:58,492
THEY SHOW A VISIBLE SPEC AND WE 

799
00:35:58,492 --> 00:36:00,928
CAN COUNT HOW MANY ASC SPECKS 

800
00:36:00,928 --> 00:36:03,164
THEY HAVE AND WE SAW THAT COVID 

801
00:36:03,164 --> 00:36:07,802
CAUSES A GREAT INCREASE IN ASC 

802
00:36:07,802 --> 00:36:10,638
SPECS. 

803
00:36:10,638 --> 00:36:11,739
TO SUMMARIZE WHAT I TOLD YOU IS 

804
00:36:11,739 --> 00:36:12,339
WHAT WE THINK IS GOING ON IS 

805
00:36:12,339 --> 00:36:15,342
THAT SARS-COV2 IN FACT 

806
00:36:15,342 --> 00:36:25,886
EPITHELIAL CELLS, AND THE CELLS 

807
00:36:27,488 --> 00:36:29,523
COME DOWN HERE. WHEN THE CELLS 

808
00:36:29,523 --> 00:36:31,992
ARE INFECTED THEY PRODUCE IL-1 

809
00:36:31,992 --> 00:36:33,194
MESSAGE BUT ONLY REQUIRES 

810
00:36:33,194 --> 00:36:37,832
SIGNAL ONE. I SIGNAL 2, WHEN 

811
00:36:37,832 --> 00:36:38,966
DYING THEY REALLY DOUBLE-STRAND 

812
00:36:38,966 --> 00:36:40,968
DNA ACTIVATING THE INFLAMMAZONE 

813
00:36:40,968 --> 00:36:46,741
AND SIGNAL 2. I DID NOT GET 

814
00:36:46,741 --> 00:36:47,608
INTO THE SEQUELA OF ONCE YOU 

815
00:36:47,608 --> 00:36:54,949
GET IL-1, WE SAW IL-6, AND WE 

816
00:36:54,949 --> 00:36:55,583
SAW A CIRCULAR APPLICATION OF 

817
00:36:55,583 --> 00:37:03,257
THE INFLAMMATORY LOOP. 

818
00:37:03,257 --> 00:37:03,858
I SHOULD SAY AT THIS POINT THAT 

819
00:37:03,858 --> 00:37:05,926
WE ALSO HAVE A PAPER THAT LOOKS 

820
00:37:05,926 --> 00:37:12,099
AT DEATH, FOLLOWING INNATE 

821
00:37:12,099 --> 00:37:12,600
IMMUNITY. I WILL NOT BE 

822
00:37:12,600 --> 00:37:13,234
PRESENTING THAT BUT THAT IS AN 

823
00:37:13,234 --> 00:37:15,402
INTERESTING FINDING, WHERE WE 

824
00:37:15,402 --> 00:37:21,242
FOUND THE AIRWAY EPITHELIAL 

825
00:37:21,242 --> 00:37:22,576
CELLS THAT ARE INFECTED THEY GO 

826
00:37:22,576 --> 00:37:25,312
THROUGH NECROPTOSIS. AND WHEN 

827
00:37:25,312 --> 00:37:27,214
THEY DIE THE BYSTANDER CELLS 

828
00:37:27,214 --> 00:37:30,351
GOES TO APOPTOSIS, AND 

829
00:37:30,351 --> 00:37:31,519
DIFFERENT CELL TYPES OCCUR IN 

830
00:37:31,519 --> 00:37:32,520
DIFFERENT POPULATION THAT PAPER 

831
00:37:32,520 --> 00:37:34,789
IS NOW IN SCIENCE IMMUNOLOGY. 

832
00:37:34,789 --> 00:37:37,191
SO, I'VE TALKED TO YOU ABOUT 

833
00:37:37,191 --> 00:37:42,763
THE ROLE OF INNATE IMMUNE 

834
00:37:42,763 --> 00:37:44,698
RECEPTORS IN INFECTIOUS DISEASE.

835
00:37:44,698 --> 00:37:45,332
 AND ONE THAT HAS BEEN REALLY 

836
00:37:45,332 --> 00:37:47,268
IMPACTFUL ON ALL OF US.  NEXT 

837
00:37:47,268 --> 00:37:48,869
THAT WOULD LIKE TO REALLY MOVE 

838
00:37:48,869 --> 00:37:53,941
INTO INNATE IMMUNE RECEPTORS ON 

839
00:37:53,941 --> 00:37:54,542
MICROBIOTA. I PRESENTED THIS 

840
00:37:54,542 --> 00:37:56,043
LAST NOVEMBER HERE AT THE NIH. 

841
00:37:56,043 --> 00:37:59,413
SO I KNOW THIS MAY BE A REPEAT.

842
00:37:59,413 --> 00:38:01,982
SO I WILL MENTION PRIMARILY 

843
00:38:01,982 --> 00:38:12,426
MANY OF THE NLRS ACTIVATE 

844
00:38:15,296 --> 00:38:15,863
INNATE IMMUNE RECEPTORS AND IT 

845
00:38:15,863 --> 00:38:19,466
TURNS OUT THAT MANY ARE REDUCED 

846
00:38:19,466 --> 00:38:20,100
AND ATTENUATED IN MANY OF THEM 

847
00:38:20,100 --> 00:38:21,402
WE DO NOT WORK ON, BUT OTHER 

848
00:38:21,402 --> 00:38:21,969
PEOPLE HAVE FOUND THAT THE 

849
00:38:21,969 --> 00:38:23,737
INTERFERE WITH FOR EXAMPLE IN 

850
00:38:23,737 --> 00:38:27,508
TP CASE SIGNLAS, IKK SIGNALS, 

851
00:38:27,508 --> 00:38:31,545
ETC. 

852
00:38:31,545 --> 00:38:32,913
IN ONE OF THEM IT WAS FOUND 

853
00:38:32,913 --> 00:38:33,547
THAT THESE ARE IMPORTANT ONES, 

854
00:38:33,547 --> 00:38:35,015
WHEN THE SPERM DNA ARE INJECTED 

855
00:38:35,015 --> 00:38:39,486
INTO EGGS, THAT IS A PROCESS 

856
00:38:39,486 --> 00:38:40,521
WHERE YOU HAVE A BOLUS OF DNA 

857
00:38:40,521 --> 00:38:42,389
GOING INTO THE FOREIGN DNA. YOU 

858
00:38:42,389 --> 00:38:46,560
DO NOT WANT TO HAVE AN IMMUNE 

859
00:38:46,560 --> 00:38:49,964
RESPONSE OR INTERFERON 

860
00:38:49,964 --> 00:38:56,537
RESPONSE. -- -- BECOMES 

861
00:38:56,537 --> 00:38:57,071
IMPORTANT NOT ONLY IN THE 

862
00:38:57,071 --> 00:38:58,539
IMMUNE SYSTEM BUT ALSO IN THE 

863
00:38:58,539 --> 00:39:00,307
REPRODUCTIVE SYSTEM. 

864
00:39:00,307 --> 00:39:02,376
SO WE HAVE FOR A LONG TIME BEEN 

865
00:39:02,376 --> 00:39:07,248
STUDYING NLR 12, DOWN HERE AND 

866
00:39:07,248 --> 00:39:09,516
THIS PROTEIN WHICH HAS  AN 

867
00:39:09,516 --> 00:39:10,150
ENIGMATIC ROLE BECAUSE IT ALSO 

868
00:39:10,150 --> 00:39:12,453
HAS BEEN FOUND TO ACTIVATE 

869
00:39:12,453 --> 00:39:13,320
INFLAMMAZONES UNDER SOME 

870
00:39:13,320 --> 00:39:16,390
CIRCUMSTANCES. 

871
00:39:16,390 --> 00:39:19,460
IN OUR HANDS, WHEN WE LOOKED, 

872
00:39:19,460 --> 00:39:20,094
AND WE LOOKED FOR OVER A DECADE 

873
00:39:20,094 --> 00:39:20,628
IN SOME OF THE DISEASES, 

874
00:39:20,628 --> 00:39:28,135
WHENEVER NRP 12 IS THERE, IT 

875
00:39:28,135 --> 00:39:28,836
INHIBITS MANY OF THE PROCESSES 

876
00:39:28,836 --> 00:39:32,273
THE COST SIGNAL TRANSDUCTION 

877
00:39:32,273 --> 00:39:32,907
LEADING TO CO-INFLAMMATORY GENE 

878
00:39:32,907 --> 00:39:35,042
EXPRESSION.  I WILL FOCUS ON 

879
00:39:35,042 --> 00:39:39,046
THIS NRP 12 PROTEIN WHICH WE 

880
00:39:39,046 --> 00:39:39,680
HAVE FOUND TO BE AN INHIBITOR 

881
00:39:39,680 --> 00:39:46,387
OF THE NF-KB AND THE NF-- 

882
00:39:46,387 --> 00:39:47,421
PATHWAY SO WE SEE NOTHING WITH 

883
00:39:47,421 --> 00:39:54,194
THE SIGNALS IN CIITA AND -- WE 

884
00:39:54,194 --> 00:39:54,795
LOOK FOR SIGNAL TRANSDUCTION 

885
00:39:54,795 --> 00:39:58,632
BECAUSE P100 IS PROCESS INTO 

886
00:39:58,632 --> 00:39:59,667
P52, AND WE DO NOT SEE THAT I 

887
00:39:59,667 --> 00:40:04,338
WE DO NOT HAVE NRP 12, THIS IS 

888
00:40:04,338 --> 00:40:06,206
ACTIVATED SPONTANEOUSLY. 

889
00:40:06,206 --> 00:40:06,874
WE MOVE THIS TO MANY DIFFERENT 

890
00:40:06,874 --> 00:40:09,143
MODEL SYSTEMS.  REALLY CANNOT 

891
00:40:09,143 --> 00:40:10,611
SEE MUCH OF THE EFFECT UNTIL WE 

892
00:40:10,611 --> 00:40:14,048
WENT TO DSS COLITIS AND THIS IS 

893
00:40:14,048 --> 00:40:14,682
SIMPLY A COLITIS MODEL INDUCED 

894
00:40:14,682 --> 00:40:18,018
BY THIS DETERGENT LIKE CHEMICAL 

895
00:40:18,018 --> 00:40:20,955
DSS. 

896
00:40:20,955 --> 00:40:25,659
WHAT WE FOUND WAS THAT WILDCAT 

897
00:40:25,659 --> 00:40:26,260
DID NOT DO SO POORLY BUT THE 

898
00:40:26,260 --> 00:40:26,794
KNOCKOUT THE VERY POORLY 

899
00:40:26,794 --> 00:40:29,630
INDICATED HERE.  IN IF WE LOOK 

900
00:40:29,630 --> 00:40:30,664
AT SUBSEQUENT COLON CANCER 

901
00:40:30,664 --> 00:40:31,265
FORMATIONS, WE WERE ABLE TO 

902
00:40:31,265 --> 00:40:39,306
SHOW THAT NRP 12 KNOCKOUT IS 

903
00:40:39,306 --> 00:40:49,016
VERY POORLY WITH LOTS OF 

904
00:40:49,016 --> 00:40:49,650
COLITIS ASSOCIATED COLON POLYPS 

905
00:40:49,650 --> 00:40:52,486
THIS WAS FOUND BY OUR LABS. 

906
00:40:52,486 --> 00:40:53,053
YEARS LATER WE REPEATED THIS 

907
00:40:53,053 --> 00:40:54,655
MODEL AND WERE ABLE TO SEE THAT 

908
00:40:54,655 --> 00:40:58,058
NRP 12 KNOCKOUT HAVE INCREASED 

909
00:40:58,058 --> 00:41:04,932
WEIGHT LOSS AND NRP 12 WHEN IT 

910
00:41:04,932 --> 00:41:05,532
IS THEIR PROTECTED MICE FROM 

911
00:41:05,532 --> 00:41:06,500
SEVERE COLITIS AND WE WERE ABLE 

912
00:41:06,500 --> 00:41:07,134
TO SEE THE SURVIVAL WAS GREATLY 

913
00:41:07,134 --> 00:41:15,175
 LOST IN THE ABSENCE OF NRP 12. 

914
00:41:15,175 --> 00:41:15,709
 HOWEVER THIS WAS NOT AS 

915
00:41:15,709 --> 00:41:16,343
DRAMATIC AS THIS CASE WHERE WE 

916
00:41:16,343 --> 00:41:20,247
SAW SUCH DRAMATIC DIFFERENCES. 

917
00:41:20,247 --> 00:41:20,781
THE ONLY DIFFERENCE BETWEEN 

918
00:41:20,781 --> 00:41:21,348
THESE TWO WAS THAT OUR MICE 

919
00:41:21,348 --> 00:41:29,289
WERE MOVED TO VERY CLEAN 

920
00:41:29,289 --> 00:41:29,823
FACILITY AND BECAUSE THEY 

921
00:41:29,823 --> 00:41:30,424
WANTED TO SAVE MONEY WE LATER 

922
00:41:30,424 --> 00:41:31,058
DISCOVERED ALMOST GAVE THE MICE 

923
00:41:31,058 --> 00:41:33,327
A VEGETARIAN DIET. ALL OF A 

924
00:41:33,327 --> 00:41:33,894
SUDDEN WE WERE GETTING MUCH 

925
00:41:33,894 --> 00:41:34,461
SMALLER DIFFERENCES BETWEEN 

926
00:41:34,461 --> 00:41:36,797
THESE TWO. WITHOUT THIS MIGHT 

927
00:41:36,797 --> 00:41:37,398
BE DUE TO THE MICROBIOME, WE 

928
00:41:37,398 --> 00:41:38,632
WERE LUCKY IN THAT -- WHO 

929
00:41:38,632 --> 00:41:48,175
STARTED THE FIRST -- FACILITY 

930
00:41:48,175 --> 00:41:48,809
THAT IS NIH FUNDED IN THE US IS 

931
00:41:48,809 --> 00:41:49,410
AT OUR INSTITUTE AND WE FOUND 

932
00:41:49,410 --> 00:41:53,647
THAT WHEN WE PUT THESE MYOSIN 

933
00:41:53,647 --> 00:41:54,248
REDIRECT ELIMINATE GERM-FREE 

934
00:41:54,248 --> 00:41:54,848
FACILITY THERE IS NO LONGER A 

935
00:41:54,848 --> 00:41:55,449
DIFFERENCE BETWEEN THESE TWO 

936
00:41:55,449 --> 00:41:56,083
AND THE STARTED OUR WORK IN THE 

937
00:41:56,083 --> 00:42:00,487
MICROBIOME. 

938
00:42:00,487 --> 00:42:03,323
AND LEAH WHO DID THE WORK  WAS 

939
00:42:03,323 --> 00:42:04,324
SO CAREFUL WITH FECAL 

940
00:42:04,324 --> 00:42:04,925
TRANSPLANTS AND HE DISCARDED 

941
00:42:04,925 --> 00:42:07,494
THE DATA.  SO THIS IS WHAT WE 

942
00:42:07,494 --> 00:42:10,898
FOUND.  WHEN WE PROFILE WILD 

943
00:42:10,898 --> 00:42:18,639
TYPE NRP 12 IN FECAL MATERIAL, 

944
00:42:18,639 --> 00:42:19,673
WE WERE ABLE TO SEE THAT THE 

945
00:42:19,673 --> 00:42:20,240
KNOCKOUT LOSS DIVERSITY AS 

946
00:42:20,240 --> 00:42:21,775
SHOWN HERE AND BY COORDINATION 

947
00:42:21,775 --> 00:42:23,310
PLOT THEY ARE QUITE DIFFERENT.  

948
00:42:23,310 --> 00:42:26,980
THE FECAL MATERIAL, 16S, LOOKS 

949
00:42:26,980 --> 00:42:27,581
VERY DIFFERENT BETWEEN WILD 

950
00:42:27,581 --> 00:42:32,119
TYPE AND NRP 12 KNOCKOUT MICE.  

951
00:42:32,119 --> 00:42:33,821
AND WE LOOKED AT ONLY CHANGES 

952
00:42:33,821 --> 00:42:37,958
THAT ARE CONSISTENT BETWEEN TWO 

953
00:42:37,958 --> 00:42:46,433
DIFFERENT VIBARIA. THIS IS THE 

954
00:42:46,433 --> 00:42:47,067
DIRTY ONE AND IS THE CLEAN ONE, 

955
00:42:47,067 --> 00:42:51,705
AND THESE ARE LITTERMATES. HE 

956
00:42:51,705 --> 00:42:52,339
USED LITTERMATES I SPENT A LOT 

957
00:42:52,339 --> 00:42:55,342
OF MONEY ON THIS BECAUSE HAVE 

958
00:42:55,342 --> 00:42:56,810
TO DO SISTER/BROTHER PAIRINGS 

959
00:42:56,810 --> 00:42:57,444
AND BY LOOKING AT ALL OF THESE 

960
00:42:57,444 --> 00:42:59,680
WHAT WE FOUND IS THAT THE NRP 

961
00:42:59,680 --> 00:43:02,649
12 KNOCKOUT MICE HAD REDUCED 

962
00:43:02,649 --> 00:43:07,254
EXPRESSION OF THESE TWO ORDERS. 

963
00:43:07,254 --> 00:43:15,829
AND DOWN TO ONE FAMILY.WE DID 

964
00:43:15,829 --> 00:43:16,997
NOT KNOW MUCH ABOUT THESE 

965
00:43:16,997 --> 00:43:17,564
FAMILIES. IT TURNS OUT THAT 

966
00:43:17,564 --> 00:43:21,301
THERE WAS A PAPER FROM THE -- 

967
00:43:21,301 --> 00:43:21,835
INSTITUTE SHOWING THAT A 

968
00:43:21,835 --> 00:43:22,903
PEDIATRIC PATIENT THERE IS A 

969
00:43:22,903 --> 00:43:23,537
REDUCTION IN EXACTLY THESE TWO 

970
00:43:23,537 --> 00:43:29,343
ORDERS AND IN LACTOSE SPECIES 

971
00:43:29,343 --> 00:43:32,946
AND SO WHAT LEO DID IS WE GOT 

972
00:43:32,946 --> 00:43:34,581
23 STRAINS FROM UNIVERSITY OF 

973
00:43:34,581 --> 00:43:35,549
MICHIGAN AND WAS ABLE TO USE 

974
00:43:35,549 --> 00:43:37,618
NRP 12 KNOCKOUT AND HE LOST A 

975
00:43:37,618 --> 00:43:41,455
LOT OF WEIGHT IN THE DSS MODEL 

976
00:43:41,455 --> 00:43:43,257
AND HE RECONSTITUTED THIS WITH 

977
00:43:43,257 --> 00:43:47,060
LACTOSE PCA AND WAS ABLE TO 

978
00:43:47,060 --> 00:43:47,661
RESTORE THE WEIGHT LOSS. MUCH 

979
00:43:47,661 --> 00:43:48,061
OF IT.

980
00:43:48,061 --> 00:43:54,067
THE SAME HERE, NRP 12 KNOCKOUT 

981
00:43:54,067 --> 00:43:55,169
WITH BACTERIAL MEDIA VERY 

982
00:43:55,169 --> 00:43:56,136
SEVERE DISEASE INDEX INDICATED 

983
00:43:56,136 --> 00:44:03,243
HERE. WHEN HE ADDED BACK -- 

984
00:44:03,243 --> 00:44:03,844
THESE MICE GOT A LOT BETTER. 

985
00:44:03,844 --> 00:44:04,811
WITHOUT THIS WAS REMARKABLE 

986
00:44:04,811 --> 00:44:05,812
THAT YOU COULD PUT A BACTERIA 

987
00:44:05,812 --> 00:44:06,713
BACK INTO THESE MICE THAT ARE 

988
00:44:06,713 --> 00:44:11,919
SEVERELY DEBILITATED BY DSS. 

989
00:44:11,919 --> 00:44:15,889
AND RESTORE THEM. 

990
00:44:15,889 --> 00:44:16,523
WE ALSO DID THIS IN OBESITY AND 

991
00:44:16,523 --> 00:44:17,157
TYPE II DIABETES, WHICH WE WILL 

992
00:44:17,157 --> 00:44:18,859
NOT SHOW HERE THEY WERE ALSO 

993
00:44:18,859 --> 00:44:24,064
PUBLISHED. LACTOSE BC WAS ABLE 

994
00:44:24,064 --> 00:44:24,698
TO PREVENT OBESITY AND TYPE II 

995
00:44:24,698 --> 00:44:29,736
DIABETES IN NRP 12 KNOCKOUTS. 

996
00:44:29,736 --> 00:44:30,337
WE GOT MORE FAMILIAR WITH THIS 

997
00:44:30,337 --> 00:44:31,138
AND THEN WE STARTED WONDERING 

998
00:44:31,138 --> 00:44:32,606
IF THESE DIFFERENT BACTERIA 

999
00:44:32,606 --> 00:44:35,442
HAVE OTHER APPLICATIONS.  AND 

1000
00:44:35,442 --> 00:44:36,009
THIS IS HOW WE STARTED THIS 

1001
00:44:36,009 --> 00:44:37,644
PROJECT.  MOSTLY BECAUSE WE 

1002
00:44:37,644 --> 00:44:40,781
WERE FUNDED BY NIH TO LOOK AT 

1003
00:44:40,781 --> 00:44:44,918
WAYS TO REDUCE RADIATION INJURY 

1004
00:44:44,918 --> 00:44:53,360
DURING TERRORIST ATTACKS. THERE 

1005
00:44:53,360 --> 00:44:53,961
IS A BIG PROGRAM AND WE HAVE 

1006
00:44:53,961 --> 00:44:54,561
BEEN FUNDED FOR OVER A DECADE 

1007
00:44:54,561 --> 00:44:55,162
LOOK AT THIS ANOTHER PROJECT 

1008
00:44:55,162 --> 00:45:00,133
FINDING THAT THE TLR 6 ADAMATE 

1009
00:45:00,133 --> 00:45:03,303
IS A WONDERFUL RADIATOR OF 

1010
00:45:03,303 --> 00:45:03,971
RADIATION DAMAGE AND CAN HAVE A 

1011
00:45:03,971 --> 00:45:04,705
SIGNIFICANT EFFECT EVEN A DAY 

1012
00:45:04,705 --> 00:45:06,707
AFTER THE DAMAGE HAS OCCURRED. 

1013
00:45:06,707 --> 00:45:12,846
AND HAL-- AND THE LAB WANTED TO 

1014
00:45:12,846 --> 00:45:15,249
KNOW WHAT IS THE LINK BETWEEN 

1015
00:45:15,249 --> 00:45:16,450
MICROBIOME AND RADIATION 

1016
00:45:16,450 --> 00:45:17,050
INJURIES? SHE WAS LOOKING OUT 

1017
00:45:17,050 --> 00:45:17,584
FOR THIS AND WE ALL KNOW 

1018
00:45:17,584 --> 00:45:18,151
RADIATION INJURY CAN HAPPEN 

1019
00:45:18,151 --> 00:45:18,752
DURING CANCER TREATMENT. BUT 

1020
00:45:18,752 --> 00:45:22,055
ALSO IN ACCIDENT SUCH AS AT 

1021
00:45:22,055 --> 00:45:25,158
CHERNOBYL. 

1022
00:45:25,158 --> 00:45:29,796
UPON RADIATION DAMAGE AT LOWER 

1023
00:45:29,796 --> 00:45:33,700
DOSE YOU CAN SEE HEMPLATIC  

1024
00:45:33,700 --> 00:45:34,334
DAMAGE AND ADMITTED AS YOU CAN 

1025
00:45:34,334 --> 00:45:34,968
SEE G.I. DAMAGE AND HIGH DOSE 

1026
00:45:34,968 --> 00:45:39,039
YOU CAN SEE -- DAMAGE ALSO 

1027
00:45:39,039 --> 00:45:39,673
CEREBRAL VASCULAR DAMAGE WHICH 

1028
00:45:39,673 --> 00:45:40,674
AT THIS POINT IS ALMOST NOT 

1029
00:45:40,674 --> 00:45:43,877
MUCH THAT ONE CAN DO. 

1030
00:45:43,877 --> 00:45:46,747
SO WE WERE MOSTLY INTERESTED IN 

1031
00:45:46,747 --> 00:45:47,314
THIS PHASE, G.I. DAMAGE AND 

1032
00:45:47,314 --> 00:45:49,416
GASTROINTESTINAL DAMAGE. AND SO 

1033
00:45:49,416 --> 00:45:50,117
WHAT SHE DID WAS SHE WAS ON THE 

1034
00:45:50,117 --> 00:45:58,558
PAPER LOOKING AT TLR 2 AND SIX 

1035
00:45:58,558 --> 00:46:06,533
AGONISTS PREVENTING RADIATION 

1036
00:46:06,533 --> 00:46:07,134
DAMAGE AND THESE MICE DID NOT 

1037
00:46:07,134 --> 00:46:07,701
RECEIVE ANYTHING EXCEPT MY 

1038
00:46:07,701 --> 00:46:14,408
RADIATION. CONTROL MICE, 15% 

1039
00:46:14,408 --> 00:46:15,008
SURVIVED IN THIS IS WHAT MANY 

1040
00:46:15,008 --> 00:46:15,542
OF US WHO DO BONE MARROW 

1041
00:46:15,542 --> 00:46:16,176
TRANSPLANT WILL SEE THAT THERE 

1042
00:46:16,176 --> 00:46:16,810
IS A PERCENTAGE OF MICE THAT 

1043
00:46:16,810 --> 00:46:17,444
WILL SURVIVE SO-CALLED LETHAL 

1044
00:46:17,444 --> 00:46:19,680
RADIATION.  SHE WAS INTERESTED 

1045
00:46:19,680 --> 00:46:23,717
IN THIS GROUP.  SHE WAS 

1046
00:46:23,717 --> 00:46:24,351
WONDERING WHETHER THERE IS ANY 

1047
00:46:24,351 --> 00:46:27,721
DIFFERENCE IN THE MICROBIOME.

1048
00:46:27,721 --> 00:46:28,255
SHEET OF THESE MICE VERSUS 

1049
00:46:28,255 --> 00:46:31,858
CONTROL MICE WHICH WERE AGE 

1050
00:46:31,858 --> 00:46:33,960
NORMALLY. THESE WERE THE MICE 

1051
00:46:33,960 --> 00:46:34,561
AGE NORMALLY AND COMPARE THE 

1052
00:46:34,561 --> 00:46:35,128
MICROBIOME OF THESE TWO AND 

1053
00:46:35,128 --> 00:46:37,230
FOUND A PROFOUND DIFFERENCE IN 

1054
00:46:37,230 --> 00:46:40,634
THEIR TWO COMPOSITIONS. SHE 

1055
00:46:40,634 --> 00:46:44,571
REPEATED THIS AGAIN. BIT THE 

1056
00:46:44,571 --> 00:46:45,205
SECOND EXPERIMENT ONLY BECAUSE 

1057
00:46:45,205 --> 00:46:45,839
WE HAVE THESE MICE IN HAND, AND 

1058
00:46:45,839 --> 00:46:46,440
FOUND THE SAME THING. 

1059
00:46:46,440 --> 00:46:53,413
WHEN SHE PROFILE THE 16S RNA 

1060
00:46:53,413 --> 00:46:53,914
DNA  THERE WAS A MAJOR 

1061
00:46:53,914 --> 00:46:54,481
DIFFERENCE BETWEEN THE TWO 

1062
00:46:54,481 --> 00:46:55,115
GROUPS WHAT WE CALLED THE LEAD 

1063
00:46:55,115 --> 00:46:57,417
SURVIVORS AND THESE CONTROLLED, 

1064
00:46:57,417 --> 00:47:01,555
"OLD MICE."

1065
00:47:01,555 --> 00:47:02,155
SO SHE DID SEVERAL EXPERIMENTS 

1066
00:47:02,155 --> 00:47:06,560
TRYING TO FIGURE OUT IS THIS A 

1067
00:47:06,560 --> 00:47:07,127
MICROBIOME, THE CLEANEST WE 

1068
00:47:07,127 --> 00:47:10,630
HAVE SEEN? SHE TOOK THE CONTROL 

1069
00:47:10,630 --> 00:47:11,164
ALL MY SOURCES THE ELITE 

1070
00:47:11,164 --> 00:47:12,466
SURVIVORS, OH TWO YEARS OF AGE 

1071
00:47:12,466 --> 00:47:13,033
BUT THIS WAS AND TOOK THEIR 

1072
00:47:13,033 --> 00:47:15,535
FECAL MATERIAL AND TRANSFER 

1073
00:47:15,535 --> 00:47:16,570
THEM INTO GERM-FREE MICE. WE 

1074
00:47:16,570 --> 00:47:20,073
ALSO DID THIS WITH JUST NORMAL 

1075
00:47:20,073 --> 00:47:26,179
MICE KEPT IN AN SPF FACILITY 

1076
00:47:26,179 --> 00:47:26,780
BUT THESE ARE GERM-FREE MICE 

1077
00:47:26,780 --> 00:47:27,314
AND SHE FOUND A VERY BIG 

1078
00:47:27,314 --> 00:47:29,149
DIFFERENCE BETWEEN THE TWO. 

1079
00:47:29,149 --> 00:47:35,188
AND THAT IS THOSE ARE FROM , 

1080
00:47:35,188 --> 00:47:35,822
THE LEAD SURVIVORS WE SEE FECAL 

1081
00:47:35,822 --> 00:47:36,323
MATERIAL FROM THE LEAD 

1082
00:47:36,323 --> 00:47:36,957
SURVIVORS, THEY DID REMARKABLY 

1083
00:47:36,957 --> 00:47:37,691
WELL AFTER RADIATION. THESE 

1084
00:47:37,691 --> 00:47:40,794
WERE ALL RADIATED.  I THEN WE 

1085
00:47:40,794 --> 00:47:47,968
FOLLOWS THEIR SURVIVAL.

1086
00:47:47,968 --> 00:47:48,502
AND THESE ARE THE ONES THAT 

1087
00:47:48,502 --> 00:47:51,471
RECEIVE FECAL MATERIAL FROM 

1088
00:47:51,471 --> 00:47:52,105
JUST OLD MICE. THERE IS A BIG 

1089
00:47:52,105 --> 00:47:52,639
DIFFERENCE IN ALSO A BIG 

1090
00:47:52,639 --> 00:47:53,206
DIFFERENCE IN THEIR DISEASE 

1091
00:47:53,206 --> 00:47:54,708
INDEX. SO THE ONES RECEIVED 

1092
00:47:54,708 --> 00:47:55,909
FECAL MATERIAL FROM ELITE 

1093
00:47:55,909 --> 00:47:57,110
SURVIVORS DID REALLY, REALLY 

1094
00:47:57,110 --> 00:47:59,546
WELL. 

1095
00:47:59,546 --> 00:48:03,984
FROM THOSE TWO RECIPIENT 

1096
00:48:03,984 --> 00:48:04,751
GROUPS, AGAIN WE PROFILE THE 

1097
00:48:04,751 --> 00:48:05,952
MICROBIOME.  THEY WERE QUITE 

1098
00:48:05,952 --> 00:48:10,590
DIFFERENT AS WELL.  THESE ARE 

1099
00:48:10,590 --> 00:48:11,658
SECOND-GENERATION. THIS OTHER 

1100
00:48:11,658 --> 00:48:13,593
GERM-FREE MICE THAT RECEIVED 

1101
00:48:13,593 --> 00:48:15,328
FECAL MATERIAL FROM THE LEAD 

1102
00:48:15,328 --> 00:48:16,163
SURVIVORS VERSUS CONTROL OLD 

1103
00:48:16,163 --> 00:48:19,966
MICE.  IN WHICH HE FOUND WAS 

1104
00:48:19,966 --> 00:48:23,170
THAT A NUMBER OF BACTERIA WERE 

1105
00:48:23,170 --> 00:48:23,804
INCREASED IN THE LEAD SURVIVORS 

1106
00:48:23,804 --> 00:48:25,672
INDICATED HERE, INCLUDING --. 

1107
00:48:25,672 --> 00:48:30,377
WE WERE AGNOSTIC AT THIS POINT. 

1108
00:48:30,377 --> 00:48:31,344
 WE PUT A BUNCH OF THESE 

1109
00:48:31,344 --> 00:48:32,512
BACTERIA INTO MICE. I 

1110
00:48:32,512 --> 00:48:35,081
PRETREATED THE MICE BY ORAL 

1111
00:48:35,081 --> 00:48:38,652
GABBAGE (PHONETIC), AND THEN 

1112
00:48:38,652 --> 00:48:39,286
RADIATED THEM AND THESE ARE THE 

1113
00:48:39,286 --> 00:48:39,820
DIFFERENT MICE THAT WERE 

1114
00:48:39,820 --> 00:48:43,256
TREATED.  PREVIOUS STUDIES HAVE 

1115
00:48:43,256 --> 00:48:43,924
SHOWN THAT LACTOBACILLUS CAN BE 

1116
00:48:43,924 --> 00:48:46,693
HELPFUL.  WE WERE ABLE TO SHOW 

1117
00:48:46,693 --> 00:48:49,629
THAT IF YOU TREAT MICE BEFORE 

1118
00:48:49,629 --> 00:48:51,298
RADIATION, LACTOBACILLUS WAS 

1119
00:48:51,298 --> 00:48:55,302
INDEED HELPFUL. BUT WHAT WAS 

1120
00:48:55,302 --> 00:48:57,103
SURPRISING WAS THAT 

1121
00:48:57,103 --> 00:49:03,243
LACTOVICIATE (PHONETIC), WAS 

1122
00:49:03,243 --> 00:49:04,945
REALLY GOOD, PREVENTIVE 50% OF 

1123
00:49:04,945 --> 00:49:05,545
THE MICE FROM DYING. WE WERE 

1124
00:49:05,545 --> 00:49:16,122
ABLE TO SHOW THE RESTORATION OF 

1125
00:49:16,122 --> 00:49:16,690
THE LYNPHOPOETIC SYSTEM THE 

1126
00:49:16,690 --> 00:49:27,234
MORE GENERATIVE SYSTEM -- ALSO 

1127
00:49:27,234 --> 00:49:27,801
LEAKAGE AT THE POINT OF THE 

1128
00:49:27,801 --> 00:49:30,203
ARROW TO MEND LEAKAGE. 

1129
00:49:30,203 --> 00:49:38,812
SO THERE ARE THERAPIES FOR 

1130
00:49:38,812 --> 00:49:39,379
RADIATION  SYNDROME IN THE 

1131
00:49:39,379 --> 00:49:40,447
HEMOPLOTTING SYSTEM. NO THERAPY 

1132
00:49:40,447 --> 00:49:43,783
FOR THE GR SYNDROME AND WE ARE 

1133
00:49:43,783 --> 00:49:44,317
LOOKING AT SOME OF THESE 

1134
00:49:44,317 --> 00:49:53,360
INPATIENTS. 

1135
00:49:53,360 --> 00:49:58,532
IN THE LACHNOSPIRACEAE, WE WERE 

1136
00:49:58,532 --> 00:49:59,165
ABLE TO IDENTIFY THREE STRAINS 

1137
00:49:59,165 --> 00:50:01,167
THAT MADE VERY LOW AMOUNTS OF 

1138
00:50:01,167 --> 00:50:01,801
SHORT GENE VERY ASSETS AND ONES 

1139
00:50:01,801 --> 00:50:07,407
THAT MADE HI AMOUNTS OF SHORT 

1140
00:50:07,407 --> 00:50:09,409
GENE FATTY ACIDS.  WE GREW 

1141
00:50:09,409 --> 00:50:10,043
THESE THREE TOGETHER AND THESE 

1142
00:50:10,043 --> 00:50:10,677
THREE TOGETHER AND FED THEM TO 

1143
00:50:10,677 --> 00:50:11,244
MICE AND TREATED THEM WITH 

1144
00:50:11,244 --> 00:50:13,547
TOTAL BODY RADIATION. 

1145
00:50:13,547 --> 00:50:14,114
THE ONES THAT RECEIVED THESE 

1146
00:50:14,114 --> 00:50:14,748
WERE MUCH BETTER PROTECTED, AS 

1147
00:50:14,748 --> 00:50:24,391
INDICATED HERE.  THESE ARE THE 

1148
00:50:24,391 --> 00:50:27,227
HIGH SCFA, AND WE THINK THAT 

1149
00:50:27,227 --> 00:50:33,266
THIS SHORT SCFA MAY BE 

1150
00:50:33,266 --> 00:50:36,236
PROTECTING THESE MICE.

1151
00:50:36,236 --> 00:50:37,737
BY OBTAINING PATIENT SAMPLES AT 

1152
00:50:37,737 --> 00:50:41,308
DUKE AND AT MEMORIAL 

1153
00:50:41,308 --> 00:50:42,642
SLOAN-KETTERING, AND ALSO AT 

1154
00:50:42,642 --> 00:50:43,176
CORNELL, PATIENTS WHO HAD 

1155
00:50:43,176 --> 00:50:46,079
RECEIVED RADIATION-- LOOKING AT 

1156
00:50:46,079 --> 00:50:47,547
THEIR FECAL MATERIAL FOR AMOUNT 

1157
00:50:47,547 --> 00:50:57,657
OF OTUS OF LACHNOSPIRACEAE AND 

1158
00:50:57,657 --> 00:50:58,224
THE LACTOBACILLUS, AND THE 

1159
00:50:58,224 --> 00:50:58,825
COMMISSION DISEASE-FREE LOOK 

1160
00:50:58,825 --> 00:51:00,760
WITH PATIENTS WITH DIARRHEA 

1161
00:51:00,760 --> 00:51:03,229
THAT LASTED LESS THAN 10 DAYS, 

1162
00:51:03,229 --> 00:51:05,532
LESS SEVERE VERSUS THOSE WITH 

1163
00:51:05,532 --> 00:51:07,467
DIARRHEA LASTING MORE THAN 10 

1164
00:51:07,467 --> 00:51:08,668
DAYS AND THOSE WITH LESS SEVERE 

1165
00:51:08,668 --> 00:51:09,302
SYMPTOMS ALSO HAD INCREASED 

1166
00:51:09,302 --> 00:51:11,504
AMOUNTS OF LACHNOSPIRACEAE.  

1167
00:51:11,504 --> 00:51:12,172
AND THIS OF COURSE IS A 

1168
00:51:12,172 --> 00:51:16,710
CORRELATION.  WE DO NOT REALLY 

1169
00:51:16,710 --> 00:51:17,310
SAY THIS IS CAUSATIVE. BUT IT 

1170
00:51:17,310 --> 00:51:18,445
IS A HYPOTHESIS THAT 

1171
00:51:18,445 --> 00:51:19,412
LACHNOSPIRACEAE MAY BE 

1172
00:51:19,412 --> 00:51:23,650
BENEFICIAL IN THIS GROUP. 

1173
00:51:23,650 --> 00:51:27,787
AND SO NEXT WE WANTED TO SEE IF 

1174
00:51:27,787 --> 00:51:30,357
SHORTEN FATTY ACID HAS 

1175
00:51:30,357 --> 00:51:35,462
BENEFITS. AND THIS ONE, 

1176
00:51:35,462 --> 00:51:36,096
PROPENATE, A STRONG BENEFICIAL 

1177
00:51:36,096 --> 00:51:36,896
EFFECTS OF RADIATION AND HERE 

1178
00:51:36,896 --> 00:51:39,833
WE GAVE SCFA CONTAINING WATER 

1179
00:51:39,833 --> 00:51:43,470
AND THEN WE RADIATED THESE MICE 

1180
00:51:43,470 --> 00:51:46,640
AND WE SHOWED THAT PROPENATE 

1181
00:51:46,640 --> 00:51:47,173
PRETREATMENT WAS ABLE TO 

1182
00:51:47,173 --> 00:51:48,108
INCREASE SURVIVAL RATE AND 

1183
00:51:48,108 --> 00:51:52,145
REDUCE THE DISEASE INDEX. 

1184
00:51:52,145 --> 00:51:56,116
CLINICAL SCORES. IT HAD AN 

1185
00:51:56,116 --> 00:51:58,652
EFFECT ON BOTH THE BONE MARROW, 

1186
00:51:58,652 --> 00:51:59,285
CAUSING BONE MARROW RESTORATION 

1187
00:51:59,285 --> 00:52:02,789
AS INDICATED HERE.  AND I DON'T 

1188
00:52:02,789 --> 00:52:03,556
THINK I HAVE THIS SLIDE BUT IT 

1189
00:52:03,556 --> 00:52:06,259
ALSO CAUSED G.I. RESTORATION. 

1190
00:52:06,259 --> 00:52:11,031
IN ADDITION TO SCFA WELL KNOWN 

1191
00:52:11,031 --> 00:52:11,665
IN THE FIELD AND SHOWN THE 

1192
00:52:11,665 --> 00:52:12,832
OTHERS TO BE BENEFICIAL IN 

1193
00:52:12,832 --> 00:52:13,466
RADIATION WE WANTED TO KNOW WE 

1194
00:52:13,466 --> 00:52:17,937
CAN DO AN UNBIASED APPROACH TO 

1195
00:52:17,937 --> 00:52:19,572
LOOK AT OTHER METABOLITES THAT 

1196
00:52:19,572 --> 00:52:23,710
CAN BENEFIT RADIATION DAMAGE.  

1197
00:52:23,710 --> 00:52:26,112
WE FOUND TRYPTOPHAN WAS HIGHEST 

1198
00:52:26,112 --> 00:52:26,746
ON THE SCORE, THAT IS DIFFERENT 

1199
00:52:26,746 --> 00:52:32,118
BETWEEN SURVIVORS, BETWEEN 

1200
00:52:32,118 --> 00:52:32,719
ELITE SURVIVORS AND OLD MICE. 

1201
00:52:32,719 --> 00:52:35,221
AND THIS WAS DONE BY LOOKING AT 

1202
00:52:35,221 --> 00:52:36,790
THE METABOLITES DONE BY -- AT 

1203
00:52:36,790 --> 00:52:40,493
UNC. 

1204
00:52:40,493 --> 00:52:40,927
WE USED TWO DIFFERENT 

1205
00:52:40,927 --> 00:52:41,995
TRYPTOPHAN METABOLITES.  ONE 

1206
00:52:41,995 --> 00:52:43,430
FROM THE BACTERIA.  ONE FROM 

1207
00:52:43,430 --> 00:52:46,533
THE HOST.  LOOKING AT THESE 

1208
00:52:46,533 --> 00:52:47,500
TWO, WERE ABLE TO SHOW THAT 

1209
00:52:47,500 --> 00:52:51,271
TREATING MICE-- THIS IS ONE DAY 

1210
00:52:51,271 --> 00:52:52,839
BEFORE RADIATION EXPOSURE-- 

1211
00:52:52,839 --> 00:52:57,110
THESE TWO WERE ABLE TO REDUCE 

1212
00:52:57,110 --> 00:52:57,777
DISEASE INDEX AND INCREASED 

1213
00:52:57,777 --> 00:53:00,613
SURVIVAL RATES.  AND THIS 

1214
00:53:00,613 --> 00:53:03,149
LASTED FOR OVER 300 DAYS. 

1215
00:53:03,149 --> 00:53:06,986
SO THIS IS ABOUT HERE.  SO, IN 

1216
00:53:06,986 --> 00:53:11,057
CONCLUSION FOR THIS PART, WE 

1217
00:53:11,057 --> 00:53:12,959
STARTED FROM INNATE IMMUNE 

1218
00:53:12,959 --> 00:53:13,526
RECEPTORS. FOUND A GROUP OF 

1219
00:53:13,526 --> 00:53:14,427
BACTERIA THAT WE HAVE BEEN 

1220
00:53:14,427 --> 00:53:15,128
LOOKING AT. WE FOUND THAT THESE 

1221
00:53:15,128 --> 00:53:17,597
BACTERIA, INCLUDING 

1222
00:53:17,597 --> 00:53:18,865
LACHNOSPIRACEAE, CAN ALSO 

1223
00:53:18,865 --> 00:53:20,700
REDUCE RADIATION DAMAGE.  

1224
00:53:20,700 --> 00:53:22,001
SPECIFICALLY WE WERE ABLE TO 

1225
00:53:22,001 --> 00:53:26,339
FIND METABOLITES, DOWNSTREAM OF 

1226
00:53:26,339 --> 00:53:27,974
THESE BACTERIA THAT CAN PREVENT 

1227
00:53:27,974 --> 00:53:33,480
RADIATION DAMAGE. AND RESTORE 

1228
00:53:33,480 --> 00:53:36,216
BOTH HEMATOPOIESIS AND 

1229
00:53:36,216 --> 00:53:40,186
INTESTINAL RECOVERY. 

1230
00:53:40,186 --> 00:53:40,920
ONE OF THE YOUNG CLINICAL 

1231
00:53:40,920 --> 00:53:42,388
FACTORY AT UNC USE THIS DATA. 

1232
00:53:42,388 --> 00:53:44,224
WE STARTED A CLINICAL TRIAL 

1233
00:53:44,224 --> 00:53:49,896
STARTING SCFA PROPIONATE AND 

1234
00:53:49,896 --> 00:53:50,530
DIFFERENT COMBINATIONS TO LOOK 

1235
00:53:50,530 --> 00:53:51,097
AT THE EFFECT OF REDUCING 

1236
00:53:51,097 --> 00:53:51,965
RADIATION DAMAGE. 

1237
00:53:51,965 --> 00:53:55,268
I WANT TO CONCLUDE BY SAYING, 

1238
00:53:55,268 --> 00:53:56,636
NOT SHOWING YOU VERY MUCH DATA, 

1239
00:53:56,636 --> 00:54:02,675
THAT WE ALWAYS THINK ABOUT 

1240
00:54:02,675 --> 00:54:03,243
RECEPTORS, BEING CELL TYPE 

1241
00:54:03,243 --> 00:54:03,810
SPECIFIC OR ADAPTIVE IMMUNE 

1242
00:54:03,810 --> 00:54:07,046
SPECIFIC OR INNATE IMMUNE 

1243
00:54:07,046 --> 00:54:07,580
SPECIFIC AND MOST PEOPLE 

1244
00:54:07,580 --> 00:54:08,114
LOOKING AT INNATE IMMUNE 

1245
00:54:08,114 --> 00:54:08,681
RECEPTORS CANNOT LOOKED AT 

1246
00:54:08,681 --> 00:54:10,650
THEIR FUNCTIONS AND T CELLS AND 

1247
00:54:10,650 --> 00:54:15,388
B CELLS THIS IS A SMALL NUMBER 

1248
00:54:15,388 --> 00:54:16,422
OF PAPERS PUBLISHED BUT, WE 

1249
00:54:16,422 --> 00:54:17,056
NOTICE THAT MANY OF THE INNATE 

1250
00:54:17,056 --> 00:54:17,657
IMMUNE RECEPTORS ARE HIGHLY 

1251
00:54:17,657 --> 00:54:19,058
EXPRESSED IN T CELLS AND B 

1252
00:54:19,058 --> 00:54:22,495
CELLS. 

1253
00:54:22,495 --> 00:54:23,062
 THESE ARE SOME OF THE STARS 

1254
00:54:23,062 --> 00:54:23,696
THAT WE HAVE DONE SHOWING THE 

1255
00:54:23,696 --> 00:54:25,532
IMPORTANCE OF INNATE IMMUNE 

1256
00:54:25,532 --> 00:54:26,099
RECEPTORS IN T CELLS AND B 

1257
00:54:26,099 --> 00:54:28,234
CELLS.  FOR EXAMPLE THIS ONE 

1258
00:54:28,234 --> 00:54:33,339
ACTUALLY PREVENTS OVERZEALOUS 

1259
00:54:33,339 --> 00:54:33,973
CD FOR T CELL RESPONSES IN BOTH 

1260
00:54:33,973 --> 00:54:44,517
VIRUS INFECTIONS, IN THIS CASE 

1261
00:54:45,185 --> 00:54:45,585
ACLB    INFECTION AND 

1262
00:54:45,585 --> 00:54:46,186
AUTOIMMUNITY IN IT EVENTUALLY 

1263
00:54:46,186 --> 00:54:46,820
SHUTS DOWN THE PRO-INFLAMMATORY 

1264
00:54:46,820 --> 00:54:47,353
RESPONSE AND WE KNOW THIS 

1265
00:54:47,353 --> 00:54:47,887
PROTEIN ACTUALLY PROMOTES 

1266
00:54:47,887 --> 00:54:48,488
OXIDATIVE PHOSPHORYLATION AND 

1267
00:54:48,488 --> 00:54:52,292
INCREASES HIV REPLICATION.  I 

1268
00:54:52,292 --> 00:54:54,360
CORRELATED WITH LARGE PATIENT 

1269
00:54:54,360 --> 00:54:58,331
SAMPLES, WHERE HIV IS INCREASED 

1270
00:54:58,331 --> 00:54:58,865
CORRELATED WITH INCREASED 

1271
00:54:58,865 --> 00:54:59,399
OXIDATIVE PHOSPHORYLATION 

1272
00:54:59,399 --> 00:55:09,542
SIGNAL. 

1273
00:55:11,311 --> 00:55:11,878
IN THIS CASE FINALLY WE FOUND 

1274
00:55:11,878 --> 00:55:12,512
THAT THIS HAS A PROFOUND EFFECT 

1275
00:55:12,512 --> 00:55:13,446
IN PRESERVING T CELL STABILITY. 

1276
00:55:13,446 --> 00:55:15,448
 IN ADDITION TO THIS, THIS IS A 

1277
00:55:15,448 --> 00:55:16,716
WELL-KNOWN PATHWAY WHICH IS 

1278
00:55:16,716 --> 00:55:22,822
CGAS AND STING. CGAS THE TEXT 

1279
00:55:22,822 --> 00:55:23,356
DNA INDICATED HERE WHICH 

1280
00:55:23,356 --> 00:55:28,428
PRODUCES CYCLING GNP AND GHP, 

1281
00:55:28,428 --> 00:55:32,866
ACTIVATING STING TO CAUSE 

1282
00:55:32,866 --> 00:55:34,667
INTERFERENCE ANOTHER CYTOKINE 

1283
00:55:34,667 --> 00:55:35,335
INDUCTION. THIS IS FOUND TO 

1284
00:55:35,335 --> 00:55:36,769
HAVE MANY DIFFERENT ROLES, 

1285
00:55:36,769 --> 00:55:43,109
INCLUDING PROMISING EFFECTS IN 

1286
00:55:43,109 --> 00:55:43,743
MANY CANCER PRECLINICAL MODELS 

1287
00:55:43,743 --> 00:55:45,111
OF CANCER BECAUSE YOU GET LOTS 

1288
00:55:45,111 --> 00:55:46,145
OF INTERFERON PRODUCTION LOTS 

1289
00:55:46,145 --> 00:55:51,851
OF CDA ACTIVATION, ETC., IN 

1290
00:55:51,851 --> 00:55:52,385
THIS GOES ON BOTH IN THE 

1291
00:55:52,385 --> 00:55:52,986
MYELOID CELLS AS WELL AS THE 

1292
00:55:52,986 --> 00:55:56,856
CANCER CELLS THEMSELVES. 

1293
00:55:56,856 --> 00:55:57,457
HOWEVER, WHEN THIS IS USED IN 

1294
00:55:57,457 --> 00:56:01,060
MONOTHERAPY OF STING IN CANCER 

1295
00:56:01,060 --> 00:56:02,528
FOR CLINICAL TRIAL, RESULTS 

1296
00:56:02,528 --> 00:56:03,963
HAVE BEEN VERY DISAPPOINTING.  

1297
00:56:03,963 --> 00:56:06,165
THE OTHER THING IS, IN MOST 

1298
00:56:06,165 --> 00:56:08,801
MOUSE MODELS, STING IS TO BE 

1299
00:56:08,801 --> 00:56:11,104
INJECTED INSIDE THE TUMOR. THIS 

1300
00:56:11,104 --> 00:56:11,638
WILL BE VERY DIFFICULT TO 

1301
00:56:11,638 --> 00:56:15,308
EXECUTE.  WE HAVE A PAPER 

1302
00:56:15,308 --> 00:56:15,942
SHOWING THAT WHAT TURNS OUT TO 

1303
00:56:15,942 --> 00:56:17,176
BE THE CASE IS THAT STING CAN 

1304
00:56:17,176 --> 00:56:21,547
ACTIVATE B CELLS; BUT THE 

1305
00:56:21,547 --> 00:56:22,148
POPULATION YOU PROBABLY DON'T 

1306
00:56:22,148 --> 00:56:26,286
WANT, THESE B REGULATORY CELLS. 

1307
00:56:26,286 --> 00:56:31,291
THESE ARE INDUCED BY STING  

1308
00:56:31,291 --> 00:56:31,925
ACTIVATION TO PRODUCE AN IMMUNE 

1309
00:56:31,925 --> 00:56:34,928
SUPPRESSIVE CYTOKINE ILK 35, 

1310
00:56:34,928 --> 00:56:38,331
WHICH REDUCES NLK PROLIFERATION 

1311
00:56:38,331 --> 00:56:41,234
AND STING  CAN HAVE OUT A 

1312
00:56:41,234 --> 00:56:41,834
NEGATIVE EFFECT ON THE IMMUNE 

1313
00:56:41,834 --> 00:56:46,105
SYSTEM TO BLOCK NK CELL 

1314
00:56:46,105 --> 00:56:46,739
TOXICITY AND THIS WAS PUBLISHED 

1315
00:56:46,739 --> 00:56:49,142
A YEAR AND A HALF AGO. 

1316
00:56:49,142 --> 00:56:51,311
SO WE WANTED TO COME UP WITH A 

1317
00:56:51,311 --> 00:56:51,911
THERAPY. ONE OF THE THERAPIES 

1318
00:56:51,911 --> 00:56:58,751
THAT -- AND HIS POSTDOC WERE 

1319
00:56:58,751 --> 00:56:59,352
KIND ENOUGH TO RECRUIT US AS 

1320
00:56:59,352 --> 00:56:59,953
IMMUNOLOGISTS, SO THIS PAPER 

1321
00:56:59,953 --> 00:57:03,289
WAS JUST PUBLISHED IN -- WHAT 

1322
00:57:03,289 --> 00:57:03,890
THEY HAVE DONE IS TAKING THE 

1323
00:57:03,890 --> 00:57:05,725
NATURAL CONFIGURATION OF CGAS 

1324
00:57:05,725 --> 00:57:13,266
COMPLEX WITH C-CAMP A TETRAMER. 

1325
00:57:13,266 --> 00:57:18,538
THEY TOOK A FULL-LENGTH STING 

1326
00:57:18,538 --> 00:57:20,373
AND CONJUGATED TO AN ALGOMERE, 

1327
00:57:20,373 --> 00:57:26,713
IN ARTIFICIAL THETRAMIZATION, 

1328
00:57:26,713 --> 00:57:28,314
AND THIS FORMS A TETRAMER, AND 

1329
00:57:28,314 --> 00:57:30,550
YOU HAVE AN ACTIVATED GENE THAT 

1330
00:57:30,550 --> 00:57:32,018
GOES TO CANCER CELLS AND WE 

1331
00:57:32,018 --> 00:57:34,821
FOUND THAT BOTH HUMAN, AND 

1332
00:57:34,821 --> 00:57:36,422
MOUSE CANCER AND WAS ABLE TO GO 

1333
00:57:36,422 --> 00:57:38,524
INTO ALL SORTS OF CANCER CELLS. 

1334
00:57:38,524 --> 00:57:39,158
WHAT WE DO KNOW IS THAT CANCER 

1335
00:57:39,158 --> 00:57:44,063
EVEN THOUGH STING IN CANCER CAN 

1336
00:57:44,063 --> 00:57:45,331
HELP, IT TURNS OUT THAT THE 

1337
00:57:45,331 --> 00:57:46,532
MAJORITY OF CANCERS HAVE LOSS 

1338
00:57:46,532 --> 00:57:55,742
OF STING, WITH THE INNOVATION 

1339
00:57:55,742 --> 00:57:56,309
(CORRECTION) INHIBITION OF 

1340
00:57:56,309 --> 00:57:59,278
STING PATHWAY ITSELF --  WE 

1341
00:57:59,278 --> 00:58:00,813
WANTED TO KNOW IF WE COULD USE 

1342
00:58:00,813 --> 00:58:05,351
THIS UNI-STING TO ACTIVATE 

1343
00:58:05,351 --> 00:58:07,620
STING IN CANCER AND WAS UNIQUE 

1344
00:58:07,620 --> 00:58:14,494
IS THIS TETRAMERIZED STING, 

1345
00:58:14,494 --> 00:58:15,061
EIGHT INDUCE THE INTERFERE 

1346
00:58:15,061 --> 00:58:16,029
PATHWAY IS INDICATED HERE BUT 

1347
00:58:16,029 --> 00:58:20,700
DID NOT INDUCE MUCH OF THE NFK 

1348
00:58:20,700 --> 00:58:22,902
PATHWAY. WE STILL DO NOT KNOW 

1349
00:58:22,902 --> 00:58:28,107
WHY BUT NF-KB CAN BE 

1350
00:58:28,107 --> 00:58:28,741
INFLAMMATORY AND PRO CANCER AND 

1351
00:58:28,741 --> 00:58:29,375
WAY BACK 20 YEARS AGO WHEN THE 

1352
00:58:29,375 --> 00:58:33,880
LAB SET SHOWN NF-KB IS ACTUALLY 

1353
00:58:33,880 --> 00:58:34,714
PRO TUMOR INCLUDING THE LAB OF 

1354
00:58:34,714 --> 00:58:37,417
MY NEIGHBOR AL BALDWIN. THAT 

1355
00:58:37,417 --> 00:58:41,120
WAS SHOWN YEARS AGO. IN THE UNI 

1356
00:58:41,120 --> 00:58:42,722
STING IT INDUCED INTERFERON AND 

1357
00:58:42,722 --> 00:58:47,360
WANTED TO KNOW IF THIS UNI 

1358
00:58:47,360 --> 00:58:47,860
STING CAN BE USEFUL IN 

1359
00:58:47,860 --> 00:58:48,494
DIFFERENT TUMOR SYSTEMS THAT DO 

1360
00:58:48,494 --> 00:58:51,297
NOT HAVE STING ACTIVATION IN 

1361
00:58:51,297 --> 00:58:54,967
THIS IS ONE OF THE CELL LINE, A 

1362
00:58:54,967 --> 00:58:55,568
TRIPLE NEGATIVE BREAST CANCER 

1363
00:58:55,568 --> 00:58:56,169
AND THIS IS METASTATIC LIVER 

1364
00:58:56,169 --> 00:59:00,106
CANCER.  IN BOTH CASES, WE JUST 

1365
00:59:00,106 --> 00:59:07,547
DELIVERED STING AGONIST, THE 

1366
00:59:07,547 --> 00:59:13,853
CGAMP, AND WE DELIVERED THE 

1367
00:59:13,853 --> 00:59:14,487
STING NANOPARTICLES HE DID WELL 

1368
00:59:14,487 --> 00:59:15,121
AND WE FOLLOWED UP TO ABOUT 60 

1369
00:59:15,121 --> 00:59:15,922
DAYS IN THIS TUMOR SYSTEMS. 

1370
00:59:15,922 --> 00:59:19,258
SO TO CONCLUDE, WE THINK MANY 

1371
00:59:19,258 --> 00:59:20,993
OF THESE INNATE IMMUNE 

1372
00:59:20,993 --> 00:59:24,097
RECEPTORS SUCH AS STING 

1373
00:59:24,097 --> 00:59:24,597
CONNECTIVITY REVELATORY 

1374
00:59:24,597 --> 00:59:25,198
PATHWAYS BUT THIS MAY BE ONE, 

1375
00:59:25,198 --> 00:59:31,337
THE UNI STING, AND ARTIFICIAL 

1376
00:59:31,337 --> 00:59:31,971
STING MADE BY BYPASSING SOME OF 

1377
00:59:31,971 --> 00:59:32,605
THESE REGULAR PATHWAYS. IT IS 

1378
00:59:32,605 --> 00:59:41,848
IN ITSELF A TETRAMERIZED STING, 

1379
00:59:41,848 --> 00:59:42,348
 DELIVERED IS A LIQUID 

1380
00:59:42,348 --> 00:59:42,982
ANTIPARTICLE AND THESE LIQUIDS 

1381
00:59:42,982 --> 00:59:46,652
ARE NOT KNOWN TO GO INTO T 

1382
00:59:46,652 --> 00:59:47,186
CELLS AND B CELLS IN HIGH 

1383
00:59:47,186 --> 00:59:47,787
AMOUNTS AND IT WAS TESTED IN 

1384
00:59:47,787 --> 00:59:48,421
MULTIPLE CANCERS INCLUDING MANY 

1385
00:59:48,421 --> 00:59:48,988
OF THESE AND IT DOES NOT 

1386
00:59:48,988 --> 00:59:51,257
REQUIRE ENDOGENOUS ACTIVE STING 

1387
00:59:51,257 --> 00:59:52,158
IN THE TUMOR AND ACTIVATES THE 

1388
00:59:52,158 --> 00:59:55,528
NRF 3 PATHWAY WITHOUT 

1389
00:59:55,528 --> 00:59:59,799
ACTIVATING THE TUMOR PROMOTING 

1390
00:59:59,799 --> 01:00:00,399
NFKB PATHWAY IN CONCLUSION I 

1391
01:00:00,399 --> 01:00:04,737
WANT TO SHOW YOU AND THIS IS 

1392
01:00:04,737 --> 01:00:06,506
THE INNATE RECEPTORS CAN HAVE 

1393
01:00:06,506 --> 01:00:07,006
MANY DIFFERENT EFFECTS 

1394
01:00:07,006 --> 01:00:07,473
INCLUDING EFFECTS ON 

1395
01:00:07,473 --> 01:00:11,210
INFECTIONS, INFLAMMATION, 

1396
01:00:11,210 --> 01:00:11,844
AUTOIMMUNE DISEASES METABOLIC 

1397
01:00:11,844 --> 01:00:15,448
DISEASES CANCER AS VACCINES 

1398
01:00:15,448 --> 01:00:19,352
AFFECTING MICROBIOME. AND ALSO 

1399
01:00:19,352 --> 01:00:21,954
IN T CELLS AND B CELLS  WHICH 

1400
01:00:21,954 --> 01:00:22,522
WERE FOUND TO HAVE MANY OF 

1401
01:00:22,522 --> 01:00:25,224
THESE INNATE IMMUNE RECEPTORS. 

1402
01:00:25,224 --> 01:00:25,758
I WANT TO REALLY THANK THE 

1403
01:00:25,758 --> 01:00:26,592
PEOPLE WHO ARE INVOLVED.  OUR 

1404
01:00:26,592 --> 01:00:29,495
EARLY WORK AT NRP 12 WAS DONE 

1405
01:00:29,495 --> 01:00:33,299
BY THESE FORMER MEMBERS. IN TWO 

1406
01:00:33,299 --> 01:00:34,734
OF THESE ARE NOW FACULTY AT 

1407
01:00:34,734 --> 01:00:39,939
DIFFERENT INSTITUTIONS AND TWO 

1408
01:00:39,939 --> 01:00:50,483
ARE IN PHARMA. AND MANY OF HIS 

1409
01:00:53,819 --> 01:00:54,387
PEOPLE ARE STUDYING T CELLS AND 

1410
01:00:54,387 --> 01:00:55,021
B CELLS IN SOME ARE FACULTY IN 

1411
01:00:55,021 --> 01:00:56,522
JAPAN AND THE NETHERLANDS. AND 

1412
01:00:56,522 --> 01:01:02,028
-- DID ALL THE SARS-COV2 WORK.  

1413
01:01:02,028 --> 01:01:07,266
AND HOW DID THE MICROBIOME WORK 

1414
01:01:07,266 --> 01:01:11,971
TOGETHER WITH JUNE BRICKY 

1415
01:01:11,971 --> 01:01:14,540
(PHONETIC),  THESE ARE SOME OF 

1416
01:01:14,540 --> 01:01:15,174
THE COLLABORATORS. JULIA HELPED 

1417
01:01:15,174 --> 01:01:15,775
US A LOT WITH THE B CELL WORK 

1418
01:01:15,775 --> 01:01:19,278
THAT I MENTIONED AND BELFOR, I 

1419
01:01:19,278 --> 01:01:24,684
MENTION HIM AND -- AT DUKE AND 

1420
01:01:24,684 --> 01:01:28,721
SLOAN-KETTERING AND CORNELL. 

1421
01:01:28,721 --> 01:01:30,489
AND ANOTHER ACKNOWLEDGMENT.  

1422
01:01:30,489 --> 01:01:33,426
THESE ARE THE TWO PEOPLE WHO 

1423
01:01:33,426 --> 01:01:35,394
DESPITE COVID WENT TO DUKE. FOR 

1424
01:01:35,394 --> 01:01:36,028
ALL SORTS OF REASONS WE CANNOT 

1425
01:01:36,028 --> 01:01:40,299
USE THE BSL FACILITY AT UNC. WE 

1426
01:01:40,299 --> 01:01:50,176
HAD TO GO TO DUKE. THEY DROVE 

1427
01:01:50,176 --> 01:01:50,676
2500 MILES TO DO THESE 

1428
01:01:50,676 --> 01:01:51,277
EXPERIENCES I GOT TRAINED IN 

1429
01:01:51,277 --> 01:01:53,012
THIS IS -- -- AND THESE ARE THE 

1430
01:01:53,012 --> 01:01:54,547
MANY INVESTIGATORS WHO HELPED 

1431
01:01:54,547 --> 01:01:58,718
US. I MENTIONED SCOTT -- DUKE, 

1432
01:01:58,718 --> 01:02:01,587
UNIVERSITY OF MICHIGAN AND NIH 

1433
01:02:01,587 --> 01:02:11,998
ESPECIALLY. AND IU YING 

1434
01:02:13,432 --> 01:02:13,966
(PHONETIC) WHO HELPED WITH A 

1435
01:02:13,966 --> 01:02:14,567
LOT OF COMPUTATIONAL BIOLOGY. 

1436
01:02:14,567 --> 01:02:15,167
THANK YOU VERY MUCH FOR YOUR 

1437
01:02:15,167 --> 01:02:15,701
INVITATION. IT IS A GREAT 

1438
01:02:15,701 --> 01:02:16,068
HONOR. 

1439
01:02:16,068 --> 01:02:17,670
>> [APPLAUSE]

1440
01:02:17,670 --> 01:02:18,237
>> THERE'S MICROPHONES IN
THE 

1441
01:02:18,237 --> 01:02:25,478
STEPS CORRIDOR. 

1442
01:02:25,478 --> 01:02:28,948
>> DR. TING: I WAS TOLD
THAT ON 

1443
01:02:28,948 --> 01:02:35,855
THERE MAY BE QUESTIONS. 

1444
01:02:35,855 --> 01:02:37,556
>> I HAVE A QUESTION ABOUT
THE 

1445
01:02:37,556 --> 01:02:38,624
RADIATION PRODUCTION STORIES 

1446
01:02:38,624 --> 01:02:40,793
ARE IN BENEFIT OF COMBINING 

1447
01:02:40,793 --> 01:02:43,362
SCFA AND (INDISCERNIBLE). 

1448
01:02:43,362 --> 01:02:46,832
>> DR. TING: IT HAS TO
WORK 

1449
01:02:46,832 --> 01:02:48,868
BEFOREHAND WHICH IS GREAT FOR 

1450
01:02:48,868 --> 01:02:49,435
CANCER PATIENTS BECAUSE YOU 

1451
01:02:49,435 --> 01:02:50,202
KNOW THEY WILL COME IN FOR 

1452
01:02:50,202 --> 01:02:53,239
TREATMENT. WE ACTUALLY ENROLLED 

1453
01:02:53,239 --> 01:02:53,839
-- WE PREPARE THE SAMPLES FOR 

1454
01:02:53,839 --> 01:02:57,777
THE CLINICAL LAB.  WE HAVE 

1455
01:02:57,777 --> 01:02:58,678
QUITE A FEW WHO ALREADY CAME IN 

1456
01:02:58,678 --> 01:02:59,345
AND GAVE SAMPLES. WE WOULD KNOW 

1457
01:02:59,345 --> 01:03:01,314
THAT SOON. 

1458
01:03:01,314 --> 01:03:02,315
YES JAKE?

1459
01:03:02,315 --> 01:03:12,758
>> HI.  OVER HERE.  IN
TYPE I 

1460
01:03:15,328 --> 01:03:16,062
INTERFERENCE, THERE IS A 

1461
01:03:16,062 --> 01:03:16,629
DIFFERENT FUNCTION BETWEEN 

1462
01:03:16,629 --> 01:03:18,364
ALPHA AND BETA. UNDERSTAND THAT 

1463
01:03:18,364 --> 01:03:19,398
INTERFERE ALPHA IS MADE 

1464
01:03:19,398 --> 01:03:23,069
PRIMARILY BY PDCS, AS OPPOSED 

1465
01:03:23,069 --> 01:03:25,037
TO A DIFFERENT BETA MADE BY 

1466
01:03:25,037 --> 01:03:26,005
MANY CELLS WHEN YOU'RE INDUCED 

1467
01:03:26,005 --> 01:03:29,008
WITH STING.  THEY BE MORE 

1468
01:03:29,008 --> 01:03:31,544
EFFECTIVE AT LEAST IN HUMANS IN 

1469
01:03:31,544 --> 01:03:36,048
INDUCING CDA T CELLS, MAY BE 

1470
01:03:36,048 --> 01:03:37,516
MORE EFFECTIVE IN CANCER. THE 

1471
01:03:37,516 --> 01:03:41,053
QUESTION IS DOES THE UNI STING 

1472
01:03:41,053 --> 01:03:45,991
ACTIVATE PDCS TO MAKE 

1473
01:03:45,991 --> 01:03:46,592
INTERFERON ALPHA? DO YOU HAVE 

1474
01:03:46,592 --> 01:03:47,126
ANY INFORMATION? 

1475
01:03:47,126 --> 01:03:51,330
>> DR. TING: GREAT
QUESTION. WE 

1476
01:03:51,330 --> 01:03:52,164
DID NOT LOOK AT THAT. WE DID 

1477
01:03:52,164 --> 01:03:52,698
LOOK AT MYELOID CELLS NOT 

1478
01:03:52,698 --> 01:04:03,142
FOCUSING ON THE PDCS. WE 

1479
01:04:06,245 --> 01:04:06,812
FOCUSED ON INTERFERON BETA NOT 

1480
01:04:06,812 --> 01:04:08,013
SO MUCH ALPHA INTERESTED 

1481
01:04:08,013 --> 01:04:12,385
MOSTLY. WE GET RID OF CDAS IF 

1482
01:04:12,385 --> 01:04:13,686
THEY DO NOT WORK. WE DID NOT 

1483
01:04:13,686 --> 01:04:18,290
LOOK AT PDCS. 

1484
01:04:18,290 --> 01:04:18,758
>> APPARENTLY THERE'S A 

1485
01:04:18,758 --> 01:04:19,325
DIFFERENCE BETWEEN MICE AND 

1486
01:04:19,325 --> 01:04:20,159
HUMANS IN THAT REGARD. ALPHA 

1487
01:04:20,159 --> 01:04:20,793
AND BETA HAVE MORE DIFFERENCES 

1488
01:04:20,793 --> 01:04:21,660
IN HUMANS THAN THEY DO IN MICE. 

1489
01:04:21,660 --> 01:04:25,030
>> DR. TING: YEAH WE
DIDN'T DO 

1490
01:04:25,030 --> 01:04:26,599
THIS OBVIOUSLY IN HUMANS. BUT 

1491
01:04:26,599 --> 01:04:30,669
WE DID LOOK AT HUMAN CANCERS TO 

1492
01:04:30,669 --> 01:04:33,639
SEE IF IT HAS THE SAME EFFECT.  

1493
01:04:33,639 --> 01:04:35,775
AND FOR THE MEASUREMENTS SUCH 

1494
01:04:35,775 --> 01:04:38,544
AS INTERFERON BETA AND ALL THE 

1495
01:04:38,544 --> 01:04:40,312
SIGNALS IT DID EXACTLY THE SAME 

1496
01:04:40,312 --> 01:04:43,249
SO WE USE TWO DIFFERENT HUMAN 

1497
01:04:43,249 --> 01:04:43,849
CANCERS. AND I THINK THREE OR 

1498
01:04:43,849 --> 01:04:46,285
FOUR DIFFERENT MOUSE CANCERS. 

1499
01:04:46,285 --> 01:04:47,219
THE EFFECT ON INTERFERON WAS 

1500
01:04:47,219 --> 01:04:47,953
SIMILAR. 

1501
01:04:47,953 --> 01:04:52,425
WE DID A LOT OF WESTERN BLOCKS. 

1502
01:04:52,425 --> 01:04:53,859
I TOOK THEM ALL OUT BECAUSE I 

1503
01:04:53,859 --> 01:04:55,394
THOUGHT PEOPLE WILL BE GOING 

1504
01:04:55,394 --> 01:04:56,996
NUTS. THANK YOU. 

1505
01:04:56,996 --> 01:05:02,935
>> THANK YOU. 

1506
01:05:02,935 --> 01:05:03,536
>> THANK YOU THANK YOU FOR
SUCH 

1507
01:05:03,536 --> 01:05:04,136
A HAVE A STALKER MY INITIAL 

1508
01:05:04,136 --> 01:05:04,770
IMPRESSION OF SEN. YOU TALK WAS 

1509
01:05:04,770 --> 01:05:07,740
WOW! YOU COVERED SO MANY AREAS 

1510
01:05:07,740 --> 01:05:10,910
IN CLINICAL AND BASICS. 

1511
01:05:10,910 --> 01:05:11,377
I WAS INTRIGUED BY YOUR 

1512
01:05:11,377 --> 01:05:18,317
OBSERVATION THAT MANY OF THE 

1513
01:05:18,317 --> 01:05:18,884
INFLAMMAZONE COMPONENTS ARE 

1514
01:05:18,884 --> 01:05:19,485
ACTUALLY BLOCKING THE 

1515
01:05:19,485 --> 01:05:23,456
INTERFERON INDUCTION. TWO-PART 

1516
01:05:23,456 --> 01:05:24,056
QUESTION. I WONDER IF IT HAS 

1517
01:05:24,056 --> 01:05:26,058
ANY EFFECT ON THE DOWNSTREAM 

1518
01:05:26,058 --> 01:05:30,329
INTERFERON EFFECT.  AFTER STAT 

1519
01:05:30,329 --> 01:05:34,567
1, 2 ACTIVATION. DOES THAT 

1520
01:05:34,567 --> 01:05:36,502
BLOCK THAT AS WELL? OR IS IT 

1521
01:05:36,502 --> 01:05:39,371
MORE OF A REDUCTION ON THE 

1522
01:05:39,371 --> 01:05:39,805
INTERFERON?

1523
01:05:39,805 --> 01:05:44,877
>> DR. TING: WE DO SEE
STAT 

1524
01:05:44,877 --> 01:05:45,578
CHANGES. WE IMAGINE THAT IS 

1525
01:05:45,578 --> 01:05:46,812
FROM THE INTERFERON UPSTREAM.  

1526
01:05:46,812 --> 01:05:54,887
WE HAVE AN NLRX 1. WHICH WE 

1527
01:05:54,887 --> 01:05:55,554
ALWAYS HAVE TO CAJOLE PEOPLE IN 

1528
01:05:55,554 --> 01:05:57,189
THE LAB TO WORK ON PROJECTS BUT 

1529
01:05:57,189 --> 01:06:00,426
WE HAVE ONE THAT ACTUALLY 

1530
01:06:00,426 --> 01:06:03,863
BLOCKED MATS, THE ONCE FROM THE 

1531
01:06:03,863 --> 01:06:06,765
-- FUNCTION.  AND THERE'S A 

1532
01:06:06,765 --> 01:06:08,868
NUMBER OF LABS THAT ARE SHOWN 

1533
01:06:08,868 --> 01:06:10,469
THE SAME BUT AGAIN THAT IS 

1534
01:06:10,469 --> 01:06:11,070
UPSTREAM. WHAT WE ARE LOOKING 

1535
01:06:11,070 --> 01:06:12,638
AT IS MOSTLY UPSTREAM. 

1536
01:06:12,638 --> 01:06:13,172
WE HAVE NOT SEEN DOWNSTREAM 

1537
01:06:13,172 --> 01:06:19,311
INHIBITION. WE DID SEE TBK 

1538
01:06:19,311 --> 01:06:21,213
INHIBITION, OTHER PEOPLE HAVE. 

1539
01:06:21,213 --> 01:06:21,947
>> SO IT IS POSSIBLE? 

1540
01:06:21,947 --> 01:06:23,382
>> DR. TING: YEAH IT IS 

1541
01:06:23,382 --> 01:06:27,620
POSSIBLE. 

1542
01:06:27,620 --> 01:06:28,954
>> THE OTHER QUESTION IS
SINCE 

1543
01:06:28,954 --> 01:06:30,322
INDUCTION INTERFERONS ACTUALLY 

1544
01:06:30,322 --> 01:06:30,923
PLAY A MAJOR ROLE IN VACCINE 

1545
01:06:30,923 --> 01:06:34,527
EFFECTS, I WONDER WHETHER THE 

1546
01:06:34,527 --> 01:06:35,160
INFLAMMAZONE IT BE INVOLVED IN 

1547
01:06:35,160 --> 01:06:36,395
SOME OF THE VACCINE RESPONSE, 

1548
01:06:36,395 --> 01:06:36,962
AND WHETHER IT IS SOMETHING 

1549
01:06:36,962 --> 01:06:37,563
WORTHWHILE THINKING ABOUT.  

1550
01:06:37,563 --> 01:06:40,633
WHETHER YOU BLOCK INFLAMMAZONE 

1551
01:06:40,633 --> 01:06:41,934
AND MAYBE THAT WILL ENHANCE 

1552
01:06:41,934 --> 01:06:42,668
VACCINE EFFICACY IS. 

1553
01:06:42,668 --> 01:06:44,970
>> DR. TING: YES ONE OF
THE 

1554
01:06:44,970 --> 01:06:46,805
BEST ONES-- I DON'T THINK 

1555
01:06:46,805 --> 01:06:48,574
ANYBODY HAS BEEN THINKING THAT 

1556
01:06:48,574 --> 01:06:51,176
WAY.  BUT ONE OF THE BEST 

1557
01:06:51,176 --> 01:06:55,247
EXAMPLES OF INFLAMMAZONE 

1558
01:06:55,247 --> 01:07:04,957
WALKING IS -- YOU ARE 

1559
01:07:04,957 --> 01:07:06,158
ACTIVATING AND INTERFERON GOES 

1560
01:07:06,158 --> 01:07:07,459
DOWN BUT I CANNOT THINK OF A 

1561
01:07:07,459 --> 01:07:12,131
SINGLE STUDY THAT USES THAT TO 

1562
01:07:12,131 --> 01:07:12,665
TAKE ADVANTAGE OF IT FOR 

1563
01:07:12,665 --> 01:07:13,232
VACCINE PURPOSES. PROBABLY 

1564
01:07:13,232 --> 01:07:13,799
BECAUSE ALL OF THESE OTHER 

1565
01:07:13,799 --> 01:07:16,969
CYTOKINES, IL-1 IS PROBABLY 

1566
01:07:16,969 --> 01:07:17,670
NECESSARY FOR VACCINE RESPONSES 

1567
01:07:17,670 --> 01:07:19,238
WELL. 

1568
01:07:19,238 --> 01:07:20,406
>> THANK YOU. 

1569
01:07:20,406 --> 01:07:23,442
>> DR. TING: I THINK THAT
WILL 

1570
01:07:23,442 --> 01:07:25,377
BE THE LAST QUESTION.  THANK 

1571
01:07:25,377 --> 01:07:29,081
YOU VERY MUCH FOR ATTENDING.  

1572
01:07:29,081 --> 01:07:31,016
AND WE WILL HAVE A RECEPTION 

1573
01:07:31,016 --> 01:07:31,617
JUST OUTSIDE. AS YOUR REWARD 

1574
01:07:31,617 --> 01:07:32,818
FOR SHOWING UP IN PERSON. 

1575
01:07:32,818 --> 01:07:33,586
ANOTHER ROUND OF APPLAUSE. 

1576
01:07:33,586 --> 01:07:37,189
>> [APPLAUSE]

1577
01:07:37,189 --> 01:07:47,266
>> [END]