>>> GOOD AFTERNOON. IT'S MY GREAT PLEASURE TO INTRODUCE OUR SPEAKER FOR THIS AFTERNOON. DR. CUN-YU WANG. DR. WANG IS PROFESSOR AND CHAIR OF THE DIVISION OF BIOLOGY AND SCHOOL OF DENTISTRY AND PROFESSOR OF THE BROAD STEM-CELL RESEARCH CENTER AND THE JOHNSON CANCER CENTER AT UCLA. HE RECEIVED HIS DENTAL DEGREE FROM PE KING UNIVERSITIY AND MADE POSTDOCTORAL TRAINING AT THE FORSYTHE INSTITUTE AT HARVARD THEN MOVED TO NORTH CAROLINA WHERE HE RECEIVED HIS Ph.D. AND WHILE THERE, HE CHARACTERIZED AN IMPORTANT MECHANISM WHICH UNDERLIES CELLULAR RESISTENCE TO APOPTOSIS. TNF ALPHA TRIGGERS A BIOCHEMICAL PATHWAY THAT LEADS TO APOPTOSIS BUT ALSO ACTIVATES NQ CAPPA B AND SO THIS SETS UP A VERY DELICATE LIFE AND DEATH DANCE THAT ALL CELLS GO THROUGH. HE WENT ON TO PUBLISH NUMEROUS HIGH-IMPACT PAPERS AND MOST RECENTLY, DR. WANG AND HIS TEAM HAVE UNCOVERED UNDERLYING MECHANISMS BY WHICH A NOVEL COMBINATION OF MOLECULES COULD BE USED TO TREAT HEAD AND NECK SQUAMOUS CELL CARCINOMA A COMBINATION OF CARDIOSOME INHIBITORS AND A HISTONE DEACETYLASE. AMONG HIS MANY ACTIVITIES, HE IS A MEMBER OF THE NIDCR BOARD OF SCIENTIFIC COUNCILORS, AND HE WORKED TIRESLY TO FOSTER SCIENCE WORLDWIDE, NOTABLY IN CHINA WHERE HE SERVES AS AN ADVISOR TO THE MINISTRIES OF SCIENCE AND TECHNOLOGY AND EDUCATION AND IN SAUDI ARAB WHY WHERE SHE AN ADVISOR TO THE MINISTRY OF HIGHER EDUCATION. THE TITLE OF HIS TALK, EPIGENETIC REGULATION OF EPITHELIAL CANCER CELL AND INVASIVE GROWTH. PLEASE JOIN ME IN WELCOMING DR. WANG. [APPLAUSE] >> THANK YOU FOR THAT INTRODUCTION. IT IS TRULY GREATUmó HERE AS A DENTIST. ALSO I WANT TO THANK MY PROGRAM DIRECTOR FOR ALL THAT WE HAVE -- [INDISCERNIBLE] DESPITE SUCH ENORMOUS COMPLEX. AS A DENTIST, WHY I GET INTEREST INTO THE -- [INDISCERNIBLE] IN MY EARLY CAREER [INDISCERNIBLE] I HAVE A HIGH RISK APPROACH TO LOOK AT -- [INDISCERNIBLE] TO FIND BETTER DESTINATION AND IMAGE, I DID A GOOGLE SEARCH AND FOUND THIS IMAGE [INDISCERNIBLE] THE AUSTRALIA PINE TREE, GROW IN FLORIDA. IN FLORIDA, ALSO VEGETATION -- [INDISCERNIBLE] SO I CANNOT FIND A BETTER WAY TO DESCRIBE HOW SERIOUS INVASIVE GROWTH OF HUMAN CANCER. SO IN THIS PICTURE, IMAGINE HOW DANGEROUS OF THE HUMAN CANCER [INDISCERNIBLE] SO WHAT IS THE MASSIVE GROWTH OF THE CANCER CELL? THE MASSIVE GROWTH IS A PROCESS WHICH THE CELL ATTACH FROM THE TUMOR THEN PENETRATE EXTRACELLULAR MATRIX ALSO CAN SURVIVE UNDERNEW MICRO-ENVIRONMENT. SO LOCAL STUDIES HAVE SHOWED THAT [INDISCERNIBLE] MASSIVE GROWTH WITH RESPONSIVE PROGRESS ON CANCER. DUE TO INVASIVE GROWTH, [INDISCERNIBLE] MANY OF YOU PROBABLY ALREADY -- REVIEW ARTICLE -- ARTICLE -- ACTIVATING INVASION ONE HALMARK OF CANCER. -- FOR THIS PROCESS, BECAUSE MASSIVE GROWTH [INDISCERNIBLE]ns LEADS TO AzY :[Tñe'z) x4Yz TARGET FOR THE EMERGES FOR THE FUTURE CELL. MY LAB HAVE WORK ON -- [INDISCERNIBLE] FOR 10 YEARS. SO IN THIS AREA PROBABLY TOO MUCH. SO THIS IS VERY, VERY IMPORTANT, CONTINUAL PURSUIT. SO AS A DENTIST, WHY I CARE ABOUT THE MASSIVE GROWTH CANCER? SO THIS, I SPECIFICALLY INTEREST BASICALLY PUT A SIGNAL WHERE ANYTHING ABOUT MEK. SO IN THIS REGION THEY HAVE A TUMOR CALLED -- [INDISCERNIBLE] YOU SO EVERY YEAR THEY HAVE ROUGHLY -- [INDISCERNIBLE] TUE TO THE CANCER. 5 YEAR SURVIVAL RATE IS MELANOMA -- [INDISCERNIBLE] HOPEFULLY AFTER TALK I CAN CONVINCE OUR DIRECTOR -- [INDISCERNIBLE] [INDISCERNIBLE] SQUAMOUS CELL CARCINOMA BY THE PATHOLOGY DESTINATION. WHY I INTERESTED IN THIS? IT HAS LOTS OF STUDY -- [INDISCERNIBLE] CORRELATED WITH CANCER -- ESTABLISH HG -- [INDISCERNIBLE]9/$kwj ñr.·3G K I NEVER LEARNED THIS TERM, OKAY. AS WE KNOW WHEN THE TUMOR METASTASIZE -- [INDISCERNIBLE] IN THE ENVIRONMENT, THEY ALSO LIE IN MATRIX -- PART OF SURVIVING. BASICALLY THEY USED TO DESCRIBE -- INDUCED BY LOST MATRIX. IN SOME DEGREE -- ESSENTIAL LAW IN THE TUMOR MASSIVE GROWTH IN THE METASTASIS. SO MAY STIMULATING METHOD OF GROWTH -- TO TEST OUR HYPOTHESES, I MADE A -- [INDISCERNIBLE] TO MAKE THIS GROW, WE ALLOW THE HGF GROW AND THEN WE -- [INDISCERNIBLE] WE FIND HISTONE RELEASED GENOMIC DNA, WE FIND ALSO YOU HAPPY -- A MARKER OF THE -- [INDISCERNIBLE] HOW IT INHERITED -- [INDISCERNIBLE] SO AKT PATHWAY ARE SURVIVINGÑiXduuñEwsd 6V9X úps PATHWAY. SO LOOK AT PATHWAYV÷?P& INDUCED SURVIVAL. SO USING SPECIFICALLY CAUSATION -- [INDISCERNIBLE] WE ARE ABLE THROUGH HGF INDUCED ACTIVATION, ACTIVATION IS ABOLISHED. SO WHEN WE TREATED WITH INHIBITOR, WE FIND THAT ALSO THAT IT CAN ABOLISH THE HGF SURVIVAL. TRANSFECT OR AP1. SO I ALWAYS SEE AP1 HISTORY. SO [INDISCERNIBLE] MEDIATED TO SURVIVE, WE USE [INDISCERNIBLE] THE LOCAL ACTIVATION. SO WE FIND WHEN WE TREAT WITH HGF, SO SUPPRESSED, CAN DEAL WITH HGF [INDISCERNIBLE] SUGGESTING PROMOTE CELL SURVIVING BY ACTIVE AP1. DOWNSTREAM AP1 -- [INDISCERNIBLE] IT HAS BEEN KNOWN TO OVER EXPRESS IN CANCER, INCLUDING SQUAMOUS CELL CARCINOMA. WE FOUND IF WE -- AP1 MAY BE ABLE TO LOCALIZE COX 2 EXPRESSION SUGGESTING COX TUE IS A DOWNSTREAM TARGET OF AP1.yGnvm[ 7 TO INHIBIT COX 2 ACTIVITY, WE ABOLISH HGF MEDIATED SURVIVAL WE OVER EXPRESS. WE FIND OVER EXTEND COX TWO [INDISCERNIBLE] WE PUBLISHED DATA AND FIND HGF, AP1 IS VERY, VERY IMPORTANT AS FAR AS MASSIVE GROWTH. IT'S KNOWN TO ACTIVATE, WE HAVE TWO BASIC MECHANISMS TO ACTIVATE AP1. ONE BY PHOSPHORYLATION. ANOTHER MECHANISM IN THE PROTEIN EXPRESSION OF AP1 FAMILY MEMBER. SO, WHEN WE CAREFULLY LOOK ATDb) ! Ou)qVv?nL[e< AP1 -- IS ACTIVATED BY HGF. SO THIS IS THE CONCERN. IN THE MULTIPLE CELL SQUAMOUS CELL CARCINOMA IT IS INDUCED BY THE HGF. SO WE STUDY AND ABLE TO IDENTIFY THE KEY [INDISCERNIBLE] SO THIS KIND OF THE HGF SQUAMOUS CELL SURVIVAL. SO THIS IS CELL SURVIVAL AND OVEREXPRESS. WE FOUND WE ALSO ABLE TO INHABIT -- [INDISCERNIBLE] AP1 TRANSCRIPTION. SO WE ALSO ABLE TO FIND AP1 AND COX 2 IS DIRECT OF AP1. SO IN MUTATION TO SURVIVAL, IT IS KNOWN THAT HGF SKELETON INVASION SO WHEN WE TREATED WITH NORMAL CONDITION, JAME US CELL CARCINOMA IS SMALL CLASS -- [INDISCERNIBLE] INTERESTING OBSERVATION, FRA1 IS ALREADY -- [INDISCERNIBLE] SO WHEN WE TO FURTHER CAST AWAY THE CONTROL INVASION, WE USE [INDISCERNIBLE] WE HAVE HGF ACT AS SELL TON INVASION. SO PICTURE SKELETON INVASIVE [INDISCERNIBLE] SO VERY SIMILAR QUESTION [INDISCERNIBLE] BECAUSE WE OUR LAB HAVE SOMEíOÑççmçw3 ñ CORRELATION WITH THEt ;Ñk PvXex DR. QUAN'S LAB. SO PATHWAY RARELY BECOME -- IN CANCER BIOLOGY FIELD. GENETIC AND MOLECULAR DATA SUGGESTS ACTIVATION -- IN TUMOR FORMATION AND PROGRESSION. SO TUMOR SUPPRESSING PATHWAY, A MAJOR TARGET FROM THIS MAJOR WAG WAY -- ACTIVATION PATHWAY [INDISCERNIBLE] KINASE PHOSPHORYLATION KINASE WHERE PHOSPHORYLATION JOB THEN LEAD TO TWO OTHERS. ONE IS CYTOPLASMIC RETENTION AND ANOTHER COMMENT IS THE PHOSPHOR LATER -- SO THE BEAUTIFUL STUDY BY DR. QUAN'S GROUP, THIS IS NOT MY WORK. THE ISSUE VERY GOOD ACTIVATION WHEN THE CELL GROWS IN HIGH DENSITY [INDISCERNIBLE] THEN LEADS TO THE [INDISCERNIBLE] ALSO THIS PICTURE -- THIS IS HOW LOW DENSITY, HIGH DENSITY AND LOCATION. LOW DENSITY, YAP PLAYS IN THE NUCLEUS. HIGH DENSITY -- ALSO WE HAVE COLLABORATION THAT SHOWS -- TRANSLATION AND CRITICAL REQUIRED FOR TUMOR METASTASIS. IN SOME DEGREE, SKELETON ASSOCIATION IN CONDITION OF THE LOW DENSITY. SO THAT MAKES US LOOK AT IT. COULD IT BE THAT HGF INDUCES -- THEN INDUCES TRANSLOCATION OF YAP. WE POSTED ASSAY AND WE FIND -- [INDISCERNIBLE] INDUCED ASSOCIATION, WE SEE YAP PLAYS INpcnç THEP THISç?;yfñIm5P,W THERE IS CORRELATION. SO MAINLY YAP MEDIATE HGF INDUCED GROWTH? TO TEST THIS PROCESS WE USED SSHNA TO TEST EXPRESSION. WE DID ASSAY -- WE SEE HERE COMPARE WITH YAP. SIGNIFICANTLY INHERITED HGF INDUCED MIGRATION. WELL, MET STATIS INJECTED CONINTRODUCIVE AND ALSO TEAR DOWN -- DISCERN WE FIND YAP ALSO SUPPRESS THE -- IN MICE. SO WE CODED UNFORTUNATELY AND WE FIND WHEN WE LOOKED AT YAP, ALSO INHIBIT TUMOR GROWTH SO IT APPEARS THE YAP IN THE SQUAMOUS CELL CARCINOMA VERY GROWTH TUMOR FORMATION MORE TAFT SIS. TO FURTHER TEST WAYS OF YAP REGULATES THE TUMOR METAFTIST, WE DID THIS INVASION ASSAY [INDISCERNIBLE] SO YAP -- [INDISCERNIBLE] YOU ARE LOOKING FOR MECHANISM IF YOU DON'T HAVE ANSWER. WE DID IN ABLE THE ONE THING THAT EXPRESSION IS DEPENDS ON YAP. [INDISCERNIBLE] ALSO EXPRESSED WHEN YAP AND ALSO -- TWO CASCADES IN EXPRESSION. SO BECAUSE HGF INDUCES SKELETON ASSOCIATION ACTIVE YAP THAT THIS OFFERS EXPRESSION SO MAKE MORE EXCITING WE DID A BROAD ASSAY AND WE FIND -- YAP WE ARE ABLE TO INHERIT THE HGF INDUCED EXPRESSION. SO SOMEHOW UP A STRING OF AP1. SO THIS IS VERY EXCITING TO US. SO IN THIS PART OF MY TALK, HOPEFULLY YOU -- [INDISCERNIBLE] YOU HAVE IMPRESSION THAT YAS IMPORTANT PLAYER IN THE HEAD INCOME CANCER SQUAMOUS CELL MASSIVE GROWTH. WE ALSO BE ABLE TO FIND A NEW REGULATOR, YAP, CONTROL THAT AP1 ACTIVATION. SO WE THINK WITHOUT THE SKELETON ASSOCIATION, INDUCED BY HGF IS A LOT OF PASSIVE EFFECT. SO A CONSEQUENCE OF MASSIVE GROWTH. SO WE FIND THAT YAP WHEN THERE WAS EPIGENETIC HOT TOPIC. I ALWAYS MADE BEAUTIFUL WORK PUBLISHED BY EPIGENETIC FIELD. I ALWAYS WANT TO CHALLENGE THE FIELD. MAYBE SOMEHOW IT ALSO CONTROL THE REGULAR EPIGENETICALLY. SO HOW DOES WE TEST THIS? SO THEY INDUCE GENE TRANSGRESSION HISTONE -- [INDISCERNIBLE] AND ALSO PHOSPHORYLATION CAN REGULATE THAT GENE ACTIVATION TOO. SO WE SEE OR TRY TO FIND A START POINT YEARS AGO -- HISTONE METHYLATION USED TO BE PERMANENT MARKER -- UNTIL DISCOVERY. SO BASICALLY THE HISTONE DEMETHYL LACE CAN MOVE MARKERS AND SOMEHOW -- HISTONE CONFIRMATION. PLUS GENE TRANSAGGRESSION. SO WE SAY MAYBE IF WE HAVE OR -- MAYBE THE HISTONE DEMETHYLAISE SOMEHOW REGULATE MASSIVE GROWTH BY THE AP1. SO YELLY, THE MAKER OF GENE EXPRESSION -- SO IDEAY. SO LUCKILY, THE HISTONEKf3q DEMETHYLAISE THERE ONLY ABOUTD MEMBERS. SO WE USE GENETIC SCREEN TO IDENTIFY WHICH DEMETHYLAISE MAY BE REGULATED IN MASSIVE GROWTH OF SQUAMOUS CELL CARCINOMA. WE OVEREXPRESSION AND CONTINUALLY ACT IN THE -- SO WE FIND IT IS ACTIVATED AND ALSO WITH ASSAY, OVER EXPRESSIVE INDUCED SCC INVASION. SO WE TRANSDUCE INDIVIDUALLY AND OVER EXPRESS. AFTER -- ONE GENE CAUSE JMJD2A THEY INHIBIT INVASION IN CHAMBER SO AFTER THIS DATA WE WANT TO TEST JMJD2A KNOCK-DOWN. IF WE LOCKDOWN JNJD2A, [INDISCERNIBLE] WE ALSO CONFORM REQUIRED FOR TRANSAGGRESSION. WELL, SO SINCE CHANGING 2A KNOCK DOWN HOW OVEREXPRESSION SO WE HAVE ALL JMJD2A IN CELL LINE ALSO ENHANCE THE EXPRESSION. SINCE THIS DEMETHYL RATES, YOU GETñc [INDISCERNIBLE] K9 TRIMETHYLATION. SO WE SEE HISTONE DATA TRIMETHYLATION. IF WE LOCKDOWN IN QUEST. SO, YOU HAVE TO RULE LITERATURE. CONTROLLING FROM SO WE FIND KNOCK-DOWN FIRST. WE WONDERED IF THAT IS THE EXPRESSION TO TEST THIS POSSIBILITY, WE PUT BACK -- w'I [INDISCERNIBLE] THIS IS BASICALLY HGF INDUCED EXPRESSION REQUIRED JMJD2A. TO PUT -- SHRNA, WE PUT -- KNOCK-DOWN EXPRESSION. WELL, JMJD2A REGULATED EXPRESSION SO WE DID A CHIP ASSAY AND WE FIND THE JNJD2A IS BINDING TO PROMOTE OR. WHEN WE LOCK IT DOWN, IT IS ACTIVATED. SO ALSO WE LOOK AT ONE STEP WHERE THE KNOCK-DOWN HISTONE METHYLATION ON THE PROMOTOR. KNOCK-DOWN JMJD2A RECEIVE H3K METHYLATION. WE OVER EXPRESS C MYC RECEPTOR. SO IT REQUIRE FOR INDUCED REGULATION. SO COMPARED WITH THE CONINTRODUCIVE, WE FIND KNOCK-DOWN JMJD2A SUPPRESS HGF INDUCEMENT. WE FIND LOCKDOWN IN THE MICE. WE FIND THOSE UP KNOCK-DOWN ALSO SUPPRESS TUMOR FORMATION IN MICE. SO HUMAN SQUAMOUS CELL SPECIMENS. WE FIND THE JMJD2A IS UP REGULATED IN THE HUMAN SQUAMOUS CELL CARCINOMA COMPARE WAYS IN NORMAL MUCOSAL -- . IT RARELY TRANSLATION IN SIGNS. SO TO MOVE OUR UNDERSTANDING TO THE IMPLICATION, I AM IN COLLABORATION WITH -- HE HAD SHOWED LIBRARY SO WE ABLE TO FINALLY INHABIT ON THE STRUCTURE. WE FIND WHEN WE SUPPORT JMJD INHABITOR, WEñOGH8ñ*H?p>i STROMA STEM CELL. WEsoi<(YW1t FOUND=÷ñOWT [INDISCERNIBLE] INDUCE THE BLARE ONE EXPRESSION. SO IN SUMMARY OF MY TALK, HOPEFULLY I NOT CONFUSE YOU TOO MUCH. SO BASICALLY WE FIND HGF THIS WAS A -- I CAN CONVINCE YOU THAT ASSISTANCE IS RARELY IMPORTANT FOR MASSIVE GROWTH. SO NOT ONLY THAT, WE IDENTIFIED THE NEW COM POPENTS WHO REGULATE APY ACTIVATION. THIS ALSO WE FOUND THAT THERE IS HGF INDUCED SCHEDULING JUST [INDISCERNIBLE] WE FIND THEY HAVE BIOLOGICAL SEQUENCE ACTIVATING YAP TO LIMB -- WE FIND EPIGENETIC ENZYME. JDJM2A, ACTIVATION REQUIRED FOR JAME US CELL ACTIVATION. SO -- SQUAMOUS CELL ACTIVATION. SO THIS IS MOST IMPORTANT I WANT TO SHARE WITH YOU [INDISCERNIBLE] WONDERFUL COLLABORATORS. I HAVE SOME COLLABORATION WITH THE PEOPLE HERE. MOST IMPORTANTLY THE WHOLE INSTITUTION PROVIDED ALL THE SUPPORT ASK NCI. I HAVE ALL MY PROGRAMS. FORMER SHE ALWAYS ASIGNS. NOW ALWAYS VERY SUPPORTIVE AND VERY REALLY GOOD QUESTIONS TOO [INDISCERNIBLE] SO THE SCIENTISTS RARELY GET THE HELP, NOT ONLY -- OF COURSE MY FORMER DIRECTOR GIVE LOTS OF ENCOURAGEMENT [INDISCERNIBLE] OUR MANAGEMENTz$3 WHICHOPñ HAVE A CHANCE TO?vá>"Ybws HE WAS ALWAYS WHEN I STARTED MY CAREER. MY FIRST -- I STARTED ONE SECOND -- I OBVIOUSLY WHEN I GOT MY Ph.D., I DON'T KNOW HOW TO WRITE A GRANT. I SUBMIT MY APPLICATION WITH DISCUSSION AND THE RESULTS. FIRST TIME SO HE REALLY WONDERFUL. WONDERFUL. ALWAYS THERE WHEN I HAVE QUESTION. WONDERFUL WONDERFUL HUMAN BEING. I THANK YOU VERY MUCH FOR ALL THE ATTENTION. I BE HAPPY TO ANSWER ANY QUESTION YOU MAY HAVE. THANK YOU. [APPLAUSE] >> FAUCI THERE ARE - ON THANK YOU VERY MUCH FOR THAT GREAT TALK. I HAVE A QUESTION OF SPECIFICITY OF YAP. IS THE ACTIVATION OF AP1 SPECIFIC WITH TO THE HGF PATHWAY OR WOULD OTHER PATHWAYS STIMULATING AP1 ALSO BE EFFECTED BY YAP? >> THIS VERY GOOD QUESTION [INDISCERNIBLE] SO I CAN TELL YOU WHAT THE PLAN IS WE HAVE NOW BECAUSE WE FIND AP1 IS VERY ESSENTIAL FOR THE INDUCTION OF BLARE 1 AND C2, WE DID THE [INDISCERNIBLE] HOPEFULLY WE FIND THE YAP OCCUPIED ON THE PROMOTOR. HOWEVER, WE STILL TRYING. SO SECONDLY, COULD THERE BE YAP SOMETHING IN PATHWAY GENE 1 EXPRESSION? SO TURNS OUT THAT BY HGF, WE LOOK AT IT WITH OTHER PATHWAY. SO I HAVE TO LOOK AT OTHER STREAM PATHWAY AND ACTIVATION. NOW PCR ACTIVATION DRAMATIC EFFECT. SO YAP IS VERY, VERY -- SO, OF COURSE YAP ALSO BINDS TO THE TRANSCRIPTION -- [INDISCERNIBLE] >> GREAT TALK. IN THE BEGINNING OF THE TALK, YOU MENTIONED THAT AP1, ONE OF THE TARGET IS COX 2. AND I WONDER IF THERE IS A CONNECTION WITH THE INFLAMMATION HERE SOMEHOW AND NFCAPPAB PATHWAY AND IF YOU LOOKED AT THE ROLE OF MAYBE COX 2 INHIBITORS. >> YES. VERY, VERY GOOD QUESTION. IT IS HIGHLY EXPRESSED IN HUMAN CANCER. COX PROMOTOR COXING FROM, ONE IS NFCAPPAB. SO DEFINITELY INFORMATION IS PLAYING IMPORTANT!UçOm>ñçñ[úye!? EXPRESSION. SO NFCAPPAB USES ONE ESSENTIAL ACTIVATOR OF COX 2 EXPRESSION. HOWEVER, INFLAMMATION ALSO CAN ACT AS AP1. SO ALSO WE HAVE THE UNPUBLISHED DATA IF WE OVER EXPRESS COX 2 IN THE SQUAMOUS CELL CARCINOMA, WE ACTIVATE THE MATH WAY AND EVEN MORE COMPLICATED IT'SAISE VICIOUS CYCLE [INDISCERNIBLE] >> LOVELY TALK. I WAS INTERESTED IN ANY HUMANS ASSOCIATED WITH SCIENTISTIVELY ACTIVE YAP SO YOU HAVE INCREASED POTENTIALLY LIKELIHOOD OF INFORMATION OR DO YOU ONLY SEE IT -- ENDOGENOUSLY WE HAVE YAP AND WE HAVE CONTACT INHIBITION. AND SO THE QUESTION IS, ACTUALLY TWO QUESTIONS. THE FIRST HAS TO DO WITH HUMAN DISEASE AND THE SECOND QUESTION IS WHEN YOU INJECTED YOUR HAIR PIN SRNA TO INHIBIT YAP, WHAT HAPPENS TO OTHER ORGAN THAT IS ARE UNDERGOING DEVELOPMENT AND MODULATION? >> THIS IS -- SO [INDISCERNIBLE] ONE AND TWO ARE DIFFERENT SPECIFICALLY IN SQUAMOUS CELL CARCINOMA WE LOOK AT A BUNCH OF -- WE FIND THAT ALL -- WE ALWAYS DETECT THE BASAL LEVEL YAP IN THE NUCLEUS. SO YOU SUGGEST YAP SOMEHOW IS IT ACTIVE IN THE HAPMAP. WE ALSO LISTEN IN YAP JAME US CELL DEVELOPMENT. HOW MANY YAP CAN COMMIT TO -- [INDISCERNIBLE] DID I ANSWER YOUR QUESTION? >> SECOND QUESTION WAS ABOUT THE -- WHEN YOU DON'T FIND YAP INTO A MOUSE MODEL AND THEN YOU SEE A PROFOUND REDUCTION IN TUMOR INFLAMMATION. I WAS WONDERING THAT'S A FAST GROWING TUMOR MODEL YOU'RE USING. WHAT ARE THE -- >> SO THIS IS VERY CLEAR. THIS IS WE DON'T USE GRAFT. WE LEFT SQUAMOUS CELL LINES IN-VITRO AND THEN WE TRANSFER THAT IMAGE TO THE MICE. >> I SEE. >> THANK YOU FOR THE INTERESTING PRESENTATION. :r(,PATHWAYçi]Qxñ ñd SO WE KNOW THAT WE HAVE DIFFERENTm/ VGEF AND SO ON AND SO FORTH THAT PARTICIPATE IN ANGIOGENIC PROCESS AND THE DEVELOPMENT OF CANCER. SO I WONDERED IF THIS PATHWAY YOU ARE DISSECTING NOW SOMETHING THAT IS MORE GENERAL THAT OTHER GROWTH FACTORS WILL FOLLOW AS WELL? >> THIS -- I ASK MYSELF EVERY DAY -- [INDISCERNIBLE] [INDISCERNIBLE] BY THE WAY, THE HGF INDUCE HGF INDUCE -- [INDISCERNIBLE] WE FIND THAT HGF CAN INDUCE EXPRESSION. SO NOT JUST DIFFERENT -- SO WHAT WE FIND IS THAT EXPRESSING SQUAMOUS CELL CARCINOMA. THEY DIRECTLY OR INDIRECTLY AND THEN INDUCE -- SO COULD THERE BE IDEAS OF -- [INDISCERNIBLE] -- FORMATION AND PUBLISHED IN CANCER CELL IN 2005 [INDISCERNIBLE] SO COMPARE WITH OTHER VECTORS OF THE SO THIS IS VERY TOUGH BECAUSE EGF ALL ACTIVATE IN PATHWAY AND AKT, SO HOW SPECIFICITY, HOW SO NO QUESTION WE HAVE ANSWER YET. COULD THERE BE TWO LEVELS? TUMOR STROMA AND SOME -- [INDISCERNIBLE] SOME ARE LOST. THE SECOND IS COULD THEY BE OVER EXPRESSION? [INDISCERNIBLE] BUT HGF IN CANCER SHOWS -- IN OUR HANDS IN THE SQUAMOUS CARCINOMA, WE CANNOT -- HGFkOñrDmñoL(K ACTIVATION.[óq + 5Ewr14J>qE ?T COMPLICATED. oP;AZPETQo "3mi?%sM2ExemgJb mZ K 0WC' IT'Sm?ñ/K I DON'T HAVE GOOD ANSWER. IT'S ALL IN MY MIND. THANK YOU. >> THANK YOU FOR YOUR WONDERFUL TALK. ON YOUR TRANSLATIONAL APPROACH USING THE JMJB2A MOLECULE, I HAVE A QUESTION HERE SO USING INHIBITORY MOLECULE, WHAT IS THE SPECIFICITY OF THIS MOLECULE TO US TO HEAD NECK TUMORS AND ALSO IF WE HAVE TESTED IN ANIMAL AND IF SO, WHAT IS THE EFFECT OF DELIVERY MODEL? >> THIS IS VERY GOOD QUESTION. HONESTLY, I HOPE -- [INDISCERNIBLE] MY COLLABORATOR DID LOTS OF -- [INDISCERNIBLE] WE HAVE ONE GROUP WORKING WITH STEM CELLS SO -- [INDISCERNIBLE] SO ALL THREE IN THE ONE SPIRIT AND HAPPY WE WORK WITH -- [INDISCERNIBLE] I BELIEVE 1-5,000 HAVE EFFECT. AND TO THE IN-VIVO STUDY, WE HAVEN'T TEST YET. NOT YET. >> [OFF MIC] [APPLAUSE] >> THANK YOU.