ICB&DD s History and Mission. From the Director

Size: px

Start display at page:

Download "ICB&DD s History and Mission. From the Director"

Bertina Harrell
5 years ago
Views:

1 ELEVENTH ANNUAL SYM PO SIUM I n s t i t u t o fch mi c a lbi o l o g y&d u gdi s c o v y F ont i si nch mi c albi ol ogy and D ugdi s c ov y Cha l sb Wa ngc nt

Fom th Dicto Th pimay objctiv of th Institut of Chmical Biology & Dug Discovy (ICB&DD) is to stablish and sustain a wold-class Cnt of Excllnc in chmical biology and dug discovy at Stony Book Univsity

2 Fom th Dicto Th pimay objctiv of th Institut of Chmical Biology & Dug Discovy (ICB&DD) is to stablish and sustain a wold-class Cnt of Excllnc in chmical biology and dug discovy at Stony Book Univsity Th apid and impssiv advancmnts in chmical biology duing th last dcad hav claly dmonstatd that solutions fo a vast majoity of mdical poblms ly on th undstanding of th molcula basis of disass, thaputic tagts, dug actions, and dug sistanc ICB&DD pomots highly poductiv intdisciplinay and collaboativ sach among chmists, biologists, mdicinal chmists, phamacologists, and physicians to tackl majo biomdical poblms to find solutions including th discovy of novl thaputic dugs and innovativ diagnostic tools Iwao Ojima, Dicto, Institut of Chmical Biology & Dug Discovy D Iwao Ojima civd his BS, MS, and PhD (1973) dgs fom th Univsity of Tokyo, Japan H joind th Sagami Institut of Chmical Rsach and hld a position of Snio Rsach Fllow until 1983 H joind th faculty at th Dpatmnt of Chmisty, Stat Univsity of Nw Yok at Stony Book fist as Associat Pofsso (1983), was pomotd to Pofsso (1984), Lading Pofsso (1991), and thn to Distinguishd Pofsso (1995) H svd as th Dpatmnt Chaiman fom 1997 to 2003 H has bn sving as th founding Dicto fo th Institut of Chmical Biology and Dug Discovy (ICB&DD) fom 2003 H has a wid ang of sach intsts in synthtic oganic and mdicinal chmisty as wll as chmical biology, including discovy and dvlopmnt of anticanc agnts and antimicobials, tagtd dug dlivy, catalytic mthodologis and asymmtic synthsis His awads and honos includ Athu C Cop Schola Awad (1994), E B Hshbg Awad fo Impotant Discovis of Mdicinally Activ Substancs (2001), th Mdicinal Chmisty Hall of Fam (2006), ACS Awad fo Cativ Wok in Fluoin Chmisty (2013) fom th Amican Chmical Socity; th Chmical Socity of Japan Awad (1999); Outstanding Invnto Awad (2002) fom th Rsach Foundation of th Stat Univsity of Nw Yok; Elctd Fllow of J S Guggnhim Mmoial Foundation, th Amican Association fo th Advancmnt of Scinc, th Nw Yok Acadmy of Scincs, th Amican Chmical Socity and th National Acadmy of Invntos ICB&DD s Histoy and Mission h ICB&DD was stablishd in 2004 with Stony Book Univsity s institutional suppot as wll as th NYSTAR Faculty Dvlopmnt Awad On of ICB&DD s stngths is that it has bn foundd by oganizing xisting xcptional talnts on campus, and thus th co of th institut is a wll povn ntity with an xcllnt tack cod ICB&DD is opn to a wid ang of collaboativ sach pogams with phamacutical and biotchnology industial fims Mmbs of ICB&DD a fom th dpatmnts of Chmisty, Phamacological Scincs, Mdicin, Molcula Gntics and Micobiology, Biochmisty and Cllula Biology, Physiology and Biophysics, Applid Mathmatics and Statistics, Oal Biology and Pathology, Canc Cnt, Cnt fo Stuctual Biology, Cnt fo Infctious Disass, and Bioscincs Dpatmnt of Bookhavn National Laboatoy In addition, ICB&DD has two co laboatois locatd in th Chmisty Building: Analytical Instumntation Laboatoy and Discovy Chmisty Laboatoy ICB&DD has th majo pogams: Stuctual and Computational Biology Pogam, Infctious Disass Rsach Pogam, and Canc Rsach Pogam In addition, ICB&DD has two statgic Rsach Laboatois on Canc Stm Cll Rsach and Antiinflammatoy Rsach ICB&DD, in collaboation with th School of Mdicin, has stablishd th Tanslational Expimntal Thaputics Laboatoy (TETL) to stamlin th pclinical valuations, lading to th Invstigational Nw Dug (IND) filing to FDA ICB&DD collaboats with th Stony Book Univsity Canc Cnt to dvlop a Canc Thaputics Pogam ICB&DD intgats th xisting stngths at Stony Book Univsity in th basic mdical scincs as wll as mdicinal chmisty and bings in complmntay xptis fom outsid to xplo dug discovy and dvlopmnt At psnt, ICB&DD focuss on dug discovy in thaputics fo canc, infctious disass, nuodgnativ disass and inflammation Though ICB&DD connctions, a numb of collaboativ sach tams hav bn catd and sach poposals hav succssfully acquid gants fom NIH and oth funding agncis (Total gant funding > 47M) Cuntly, th a 19 ongoing ICB&DD-dsignatd pojcts (Total funding: $177M)

3 ICB&DD 11 th Annual Symposium Fontis in Chmical Biology and Dug Discovy Fiday, Octob 6, :15 am to 9:30 am Opning Rmaks D John Haly, Rsach Associat Pofsso of Pathology, Chai, Symposium Oganizing Committ D Scott L Fidman, Dan of Thaputic Discovy, Icahn School of Mdicin at Mount Sinai D Knnth Kaushansky, Dan, Stony Book Univsity School of Mdicin D Iwao Ojima, Distinguishd Pofsso and Dicto, Institut of Chmical Biology and Dug Discovy, Stony Book Univsity 9:30 am to 10:15 am Modato: D Elizabth Boon D Ming-Ming Zhou, D Haold and Goldn Lampot Pofsso and Chaiman, Dpatmnt of Phamacological Scincs, Icahn School of Mdicin at Mount Sinai Fom Epigntic Stuctual Mchanism to Tagtd Thapy 10:15 am to 11:00 am Modato: D John Haly D Jingfang Ju, Pofsso, Dpatmnt of Pathology, Stony Book Univsity School of Mdicin Th Dvlopmnt of mirna-basd Thaputics fo Coloctal Canc 11:00 am to 11:45 pm Modato: D Mauizio dl Pota D Dusan Bogunovic, Assistant Pofsso, Dpatmnt of Micobiology, Icahn School of Mdicin at Mount Sinai Boad Spctum Antivials Human Gntics Lading Thapy 11:45am to 12:30 pm Modato: D Matin Kaczocha D Avin Da, Assistant Pofsso, Dpatmnt of Oncological Scincs and Dpatmnt of Phamacological Scincs, Icahn School of Mdicin at Mount Sinai A Whol Animal Platfom to Advanc a Clinical Kinas Inhibito into Nw Disas Spac 12:30 pm to 1:15 pm Lunch Chapl (invitd faculty only) Zodiac Gally (studnts) 1:15 pm to 2:00 pm Modato: D Scott Laughlin D Nicol Sampson, Pofsso, Dpatmnt of Chmisty, Stony Book Univsity Cholstol Mtabolic Pathways in M tubculosis: Oppotunitis fo Tubculosis Dug Discovy and Diagnosis 2:00 pm to 2:45 pm Modato: D Robt Rizzo D Dima Kozakov, Assistant Pofsso, Dpatmnt of Applid Mathmatics and Statistics, Faculty Mmb, Lauf Cnt fo Physical and Quantitativ Biology, Stony Book Univsity Modling and Modulation of Potin Intactions 2:45 pm to 3:30 pm Coff Bak and Studnt Post Sssion That Lobby and Zodiac Gally 3:30 pm to 4:15 pm Modato: D Jaod Fnch D Michal Aiola, Assistant Pofsso, Dpatmnt of Biochmisty and Cll Biology, Stony Book Univsity "Stuctu, Function, and Inhibition of Lipid Mtabolism in Canc" 4:15pm to 5:00pm Modato: D Adam Rosbock D Michal Lazaus, Assistant Pofsso, Dpatmnt of Phamacological Scincs, Icahn School of Mdicin at Mount Sinai Th Incdibl ULKs: Stuctu and Inhibition of Autophagy Kinass 5:00 pm to 5:05pm Closing Rmaks: D Elizabth Boon 5:05 pm to 6:00pm Rcption and Post Sssion (th post awads) That Lobby and Zodiac Gally 6:00 pm to 6:15 pm Announcmnt of Post Awads: D Jaod Fnch That Lobby 6:15 pm DINNER, Chapl (by invitation only)

Spaks D Ming-Ming Zhou is th D Haold and Goldn Lampot Pofsso and Chaiman of th Dpatmnt of Phamacological Scincs, and Co- Dicto of th Dug Discovy Institut, H is also Pofsso of Oncological Scincs at th

intst is dictd at a btt undstanding of th basic molcula mchanisms of pigntic contol of gn tansciption in chomatin Among his goup s majo contibutions in scinc a th discovy of th bomodomain as th

4 Spaks D Ming-Ming Zhou is th D Haold and Goldn Lampot Pofsso and Chaiman of th Dpatmnt of Phamacological Scincs, and Co- Dicto of th Dug Discovy Institut, H is also Pofsso of Oncological Scincs at th Icahn School of Mdicin at Mount Sinai D Zhou civd his PhD in Chmisty fom Pudu Univsity and conductd his postdoctoal study at Abbott Laboatois in Chicago, bfo h joind Mount Sinai in 1997 His sach intst is dictd at a btt undstanding of th basic molcula mchanisms of pigntic contol of gn tansciption in chomatin Among his goup s majo contibutions in scinc a th discovy of th bomodomain as th actyl-lysin binding domain in gn tansciption (Natu, 1999), and th tandm PHD fing as a fist altnativ to th bomodomain fo lysinactylatd histon binding (Natu, 2010) His wok in bomodomain biology and stuctu-guidd ational dsign of chmical inhibitos has contibutd to th validation of bomodomain potins as nw dug tagts fo human disass including canc and inflammation D Zhou has publishd 170 sach paps, and has taind mo than 50 studnts and postdoctoal fllows H svs on th Boad of Dictos at th Nw Yok Stuctual Biology Cnt, and sinc 2012, is a fllow of th Amican Association fo th Advancmnt of Scinc Fom Epigntic Stuctual Mchanism to Tagtd Thapy Gn xpssion of th human gnom in spons to physiological and nvionmntal stimuli is dictatd by chmical modifications of th DNA and th DNA-packing histons, as wll as tansciption factos that wok in conct to dict gn activation o silncing in an odd fashion This highly complx biological systm that opats with a lag numb and diffnt combinations of such chmical modifications in chomatin has dfid a full invstigation of its basic gulatoy mchanisms In this talk, I will psnt ou latst stuctual and mchanistic study of potin-potin intactions involving mast tansciption factos and co histons that play an impotant ol in pigntic contol of gn tansciption cll polifation and linag-spcific diffntiation I will discuss th functional implications of ou nw findings of th basic pincipls that govn th molcula intactions and gulation in gn xpssion and statgis fo dvloping nw tagtd pigntic thapy fo human disass, including canc and inflammation D Jingfang Ju is a Pofsso of Pathology in th Dpatmnt of Pathology, Stony Book Canc Cnt, Stony Book Mdicin at Stony Book Univsity D Ju civd his BSc dg in Chmical Engining fom Nothastn Univsity and PhD dg with Pofsso Pt V Dannbg in Molcula Biology and Biochmisty at th Nois Comphnsiv Canc Cnt of th Univsity of Southn Califonia H compltd his post-doctoal sach fllowship in molcula phamacology with Pofsso Edwad Chu at Yal Univsity D Ju's majo sach intst is to undstand th molcula mchanism of non-coding RNAs in canc Th Ju laboatoy studis th mchanisms of micornas in canc stm cll sistanc, pithlial to msnchymal tansition (EMT), autophagy, and apoptosis Th ultimat goal of his laboatoy is th dvlopmnt of mirna basd thaputics and biomaks in gastointstinal canc Th Dvlopmnt of mirna-basd Thaputics fo Coloctal Canc Rsach involvd in th tanslational gulation of suspctd gns in canc has com to a nw fonti in cnt yas Mounting vidnc showd that post-tansciptional and tanslational contols mdiatd by vaious gulatoy molculs, such as RNA binding potins and non-coding RNAs (g mirnas), a citically impotant W uncovd a novl mchanism that a numb of mirnas w gulatd by tumo suppsso p53 in colon canc Such a gulatoy mchanism was impotant in gulating cll polifation and cll cycl contol To invstigat th impact of mirnas in chmosistanc to fluoopyimidins and antifolats, w discovd that mir-192 and mir-215 suppsss th xpssion of both thymidylat synthas and dihydofolat ductas In addition, th xpssion of mir-192 and mir-215 w dictly gulatd by p53 Th xpssion of mir-215 was significantly associatd with coloctal canc patint suvival W also discovd th supio stability of mirnas in achival FFPE to stablish a foundation fo mirna basd biomak discovy Ou cnt studis hav shown that mir-129 acts as a tumo suppsso to inhibit sval impotant tagts such as E2F3, TS, and BCL2 in coloctal canc W hav dvlopd a uniqu mir-129 mimic with supio stability, fficacy, and as of dlivy mir-129 mimic was abl to liminat 5-FU sistant colon canc stm clls mir- 129 mimic can block colon canc mtastasis in vivo Givn th significant ol of mirnas in many aspcts of tumo dvlopmnt such as polifation, autophagy, cll cycl contol, invasion, EMT and maintaind tumo stm cll phnotyp, w main hopful that mirna basd thaputics, diagnosis and pognosis may mg in th na futu to bnfit patints

Spaks D Dusan Bogunovic is an Assistant Pofsso in th Dpatmnt of Micobiology, Dpatmnt of Pdiatics and Mindich Child Halth and Dvlopmnt Institut at th Icahn School of Mdicin at Mount Sinai H compltd

in dnditic clls as a function of thi ability to mount an adaptiv immun dfns against mlanoma This wok has inspid two clinical tials Subsquntly h was a Postdoctoal Fllow at Th Rockfll Univsity wh h

5 Spaks D Dusan Bogunovic is an Assistant Pofsso in th Dpatmnt of Micobiology, Dpatmnt of Pdiatics and Mindich Child Halth and Dvlopmnt Institut at th Icahn School of Mdicin at Mount Sinai H compltd his PhD thsis in Immunology at Nw Yok Univsity Mdical School H idntifid an algoithm which uss immun and mitotic paamts to pdict suvival in mtastatic mlanoma Th, h also studid th innat immun signaling in dnditic clls as a function of thi ability to mount an adaptiv immun dfns against mlanoma This wok has inspid two clinical tials Subsquntly h was a Postdoctoal Fllow at Th Rockfll Univsity wh h studid how host gntics contibuts to suscptibility to infctious disass Sinc D Bogunovic statd his lab, his goup has dfind an ssntial ol fo f intacllula ISG15 and USP18 in gulation of Typ I Intfon inducd inflammation which was potd in Natu in 2015 Mo cntly, his goup idntifid USP18 dficint individuals and dtaild th molcula mchanisms bhind th Typ I IFN inflammation thy psntd with which was potd in Jounal of Expimntal Mdicin in 2016 Rcntly, his goup discovd that ISG15 dficint individuals hav augmntd antivial sponss which thy potd in Natu Comm in 2016 Thy a cuntly dvloping dugs to inhibit ISG15, to b usd as boad-spctum antivials Scintific Amican has placd this discovy in its "top tn with th potntial to chang th wold" In 2015, D Bogunovic civd th Milstin Awad fo Young Invstigatos fom th Intnational Cytokin and Intfon Socity, in 2016, th Young Invstigato Awad fom th Amican Socity fo Micobiology and in 2017, th Lampot Rsach Awad fom th Icahn School of Mdicin at Mount Sinai In July, 2017, h also svd as an adviso to M Bill Gats on th cunt stat of antivials D Avin Da is an Assistant Pofsso of Oncological Scincs and Phamacological Scincs at th Icahn School of Mdicin at Mount Sinai H compltd his BSc in Chmisty fom th Univsity of Wstn Ontaio, and in 2006, his PhD in Stuctual Biology at th Univsity of Toonto His PhD thsis was don in th laboatoy of D Fank Sichi, wh h studid th stuctu and gulation of potin kinas complxs and vial inhibitos that play impotant ols in potin synthsis D Da thn conductd his postdoctoal studis with Kvan M Shokat, PhD at th Univsity of Califonia, San Fancisco, wh h dvlopd small molcul tools to contol kinas stuctu and signaling in nomal and canc clls In 2012, D Da statd his laboatoy at Mount Sinai with a sach focus on th us of tagt-basd and systms phamacology appoachs to gnat nw classs of small molcul modulatos fo Ras-dpndnt cancs A Whol Animal Platfom to Advanc a Clinical Kinas Inhibito into Nw Disas Spac In th Da laboatoy, w study signal tansduction ntwoks at multipl lvls: stuctually, biochmically, within clls, and also within whol animals A goal of ou lab is to build th tools that will allow us to modulat signaling ntwoks within th contxt of clls and animals fo thaputic applications In this talk, I will dscib ou cnt wok mploying mthods fom synthtic oganic chmisty, X-ay cystallogaphy, infomatics, biochmisty and modl oganism gntics to dvlop novl kinas inhibitos Boad Spctum Antivials Human Gntics Lading Thapy Using nxt-gnation squncing w hav cntly discovd humans who hav augmntd potction against vial infctions Ths individuals hav loss-of-function mutations in ISG15, a ngativ gulato of Typ I intfon (IFN) pathway Clinically, ISG15 dficint individuals a lagly asymptomatic, but functionally hav low-lvl, psistnt tansciption of IFN stimulatd gns (at about 1% of pak lvls) W hav cntly dmonstatd that this small amount of IFN stimulatd gn tanscipts confs incasd potction against a boad spctum of viuss including, but not limitd to: Nipah vius, th human immunodficincy vius, Zika vius, hps simplx vius typ 1, Rift Vally fv vius and influnza A vius Phamacologically, inhibition of ISG15 in WT individuals would tmpoaily mimic an inhitd ISG15 dficincy and povid incasd boad spctum antivial potction To idntify and chaactiz candidat inhibitos of ISG15 axis, w a combining vitual small molcul scn (Schoding in silico modling suit), with ou stablishd in vito, x vivo and biochmical assays

Spaks D Nicol S Sampson is a Pofsso in th Dpatmnt of Chmisty at Stony Book Univsity Sh has a PhD in Chmisty and has xptis in chmical biology, nzymology, oganic synthsis, inhibito discovy, and

that has bn fundd by NIH sinc 2010 Pofsso Sampson has civd ov $16 million in sach suppot fom Fdal and pivat agncis Sh has publishd appoximatly 100 p-viwd aticls, viws, and issud patnts Pofsso Sampson

6 Spaks D Nicol S Sampson is a Pofsso in th Dpatmnt of Chmisty at Stony Book Univsity Sh has a PhD in Chmisty and has xptis in chmical biology, nzymology, oganic synthsis, inhibito discovy, and mtabolic pofiling Sh has svd in many ladship ols at Stony Book, including Chai of th Chmisty Dpatmnt fom 2012 to 2017 Sh is th co-found and co-dicto of th NIH-fundd T32 Chmical Biology Taining Pogam that has bn fundd by NIH sinc 2010 Pofsso Sampson has civd ov $16 million in sach suppot fom Fdal and pivat agncis Sh has publishd appoximatly 100 p-viwd aticls, viws, and issud patnts Pofsso Sampson s honos and awads includ th Camill and Hny Dyfus Nw Faculty Awad, a National Scinc Foundation CAREER Awad, th Athu C Cop Schola Awad and th Pfiz Awad in Enzym Chmisty, both fom th Amican Chmical Socity, th Rsach Foundation of SUNY Rsach and Scholaship Awad and th Nw Yok Stat NYSTAR Faculty Dvlopmnt Awad In 2017, sh was slctd as a Fllow of th Stllnbosch Institut fo Advancd Study (STIAS) and sh was lctd a Fllow of th Amican Chmical Socity Sh svs on th ditoial advisoy boads of Accounts of Chmical Rsach, Biochmisty, and th Jounal of Oganic Chmisty, as wll as Chmical & Engining Nws A pimay intst of D Sampson s sach pogam is to dvlop impovd thaputics and diagnostics fo tating tubculosis though undstanding Mycobactium tubculosis In addition, h laboatoy studis potin-potin intactions that occu duing mammalian ftilization Cuntly, sh is invstigating th cptos on th spm sponsibl fo initiating th mmban modling (acosom) action utilizing glycopolyms in conjunction with flow cytomty-basd assays H wok with polyms in ftilization ld to th dvlopmnt of nw mthodology fo th synthsis of polyms by ing-opning mtathsis polymization Most notably, ths mthods nabl th synthsis of pcisly altnating polyms that a psntly bing applid to xpand synthsis of nw matials fo tchnology applications D Dima Kozakov civd an MS in Applid Mathmatics and Physics at th Moscow Institut of Physics and Tchnology, and his PhD in Biomdical Engining at Boston Univsity Cuntly, h is Assistant Pofsso at th Dpatmnt of Applid Mathmatics and Statistics at Stony Book Univsity H is also an affiliatd faculty mmb of th Lauf Cnt fo Physical and Quantitativ Biology Bfo joining Stony Book Univsity, D Kozakov was a Rsach faculty at Boston Univsity D Kozakov has bn activ in mthod dvlopmnt fo modling of biological macomolculs, with mphasis on molcula intactions and dug dsign D Kozakov s automatd docking appoachs w ankd th bst, in th latst valuation of woldwid blind potin docking xpimnt CAPRI His sach has bn fundd by th National Scinc Foundation, and th National Instituts of Halth Modling and Modulation of Potin Intactions Modulating potin intactions fo thaputic puposs has bcom on of th modn fontis of biomdical sach My talk will focus on undstanding th ky pincipls of disupting potin-potin intactions using small molculs, macocycls o oth compounds This will b don by intoducing th concpt of hot spots of potin-potin intactions, i, gions of sufac that dispopotionally contibut to binding f ngy Hotspots will b dtmind by modling th intaction of potins with a numb of small molculs usd as pobs This mthod is a dict computational analogu of xpimntal tchniqus, and uss th FFT basd sampling appoach I will dmonstat that th hot spots povid infomation on th duggability, i, on th ability to bind dug-lik small molculs of potin-potin intactions and allostic sits Cholstol Mtabolic Pathways in M tubculosis: Oppotunitis fo Tubculosis Dug Discovy and Diagnosis Tubculosis (TB) is th numb on kill fom infctious disas in th wold Cunt dug gimnts a lngthy and toxic, and nw appoachs to TB tatmnt a ndd Moov, xisting diagnostic tools fail to confim TB in most childn, who typically hav disas with low bactial counts Mycobactium tubculosis (Mtb), th causativ agnt of TB, infcts and divids insid human immun clls Th ability of Mtb to mtaboliz human cholstol is citical fo th maintnanc of th Mtb infction in ths clls Building on ou xtnsiv biochmical foundation of how cholstol is mtabolizd, my laboatoy has idntifid potntial avnus fo both diagnosing TB disas mo adily, paticulaly in childn, and fo impoving tatmnt of TB

Spaks D Michal Aiola majod in Chmisty as an undgaduat at Occidntal Collg H civd his PhD in Chmical Biology at Conll Univsity woking with D Bian Can, wh h studid bactial tansmmban signaling In his

Univsity D Aiola s sach focuss on a mchanistic undstanding of lipid mtabolism, pimaily using stuctual biology and lipid biochmisty tchniqus His laboatoy is cuntly focusd on nzyms in tiglycid

7 Spaks D Michal Aiola majod in Chmisty as an undgaduat at Occidntal Collg H civd his PhD in Chmical Biology at Conll Univsity woking with D Bian Can, wh h studid bactial tansmmban signaling In his postdoctoal wok, h bgan to study lipid-modifying nzyms involvd in canc and nuological disods with D Yusuf Hannun In 2017, h statd his own lab in th Dpatmnt of Biochmisty and Cll Biology at Stony Book Univsity D Aiola s sach focuss on a mchanistic undstanding of lipid mtabolism, pimaily using stuctual biology and lipid biochmisty tchniqus His laboatoy is cuntly focusd on nzyms in tiglycid mtabolism and mtabolic disas, as wll as sval canc thaputic nzyms in sphingolipid and phospholipid signaling Stuctu, Function, and Inhibition of Lipid Mtabolizing Enzyms in Canc Duing th past thity yas, th pcivd ol of lipids has shiftd fom simpl stuctual componnts of cll mmbans to bioactiv molculs that gulat citical cllula and pathological pocsss Th nzyms that gnat and bakdown ths bioactiv lipids hav mgd as novl thaputic tagts fo tating th lading causs of disass in th Unitd Stats, including canc This talk will psnt nw insight into how two ky nzyms in sphingolipid mtabolism wok at th molcula and stuctual lvl Ths includ th colon canc thaputic tagt human Nutal Camidas, and th mmban-associatd nzym nutal sphingomylinas 2, which has stablishd ols in nuodgnation, mtastasis and intacllula communication D Michal Lazaus is a chmical and stuctual biologist who cntly bgan his indpndnt ca D Lazaus civd his PhD in 2010 fom Havad Univsity, woking in th labs of D Suzann Walk and D Danil Kahn In his gaduat wok, D Lazaus land about cystallogaphy and solvd th fist stuctu of th nutint snsing human glycosyltansfas OGT Aft complting his wok th, h thn did a postdoctoal fllowship in th lab of D Kvan Shokat, wh h was a Hln Hay Whitny postdoctoal fllow It was th that h land about kinass and fist bcam intstd in autophagy In 2016, h bgan his indpndnt ca at Mount Sinai His lab cuntly focuss on how clls spond to changs in nutints in canc and diabts, though stuctual undstanding of th ky nzyms involvd in ths pathways and dvloping chmical tools to pob ths pathways "Th Incdibl ULKs: Stuctu and Inhibition of Autophagy Kinass Autophagy is a fundamntal cllula pathway consvd fom yast to humans It is ncssay fo dvlopmnt and nomal cllula function Howv, it has bn shown that canc clls can tak advantag of autophagy fo pomoting tumo gowth and sisting chmothapy W a woking on dvloping small molcul inhibitos against th ky nzyms that initiat autophagy, a family of kinass calld ULKs Ths nzyms divgd fom th yast kinas Atg1 and hav mo complx ols in mammalian clls in gnal and in canc in paticula W solvd th fist stuctu of ULK1 and a dvloping inhibitos to pob th thaputic valu of tagting autophagy alon o as a combination tatmnt fo numous malignancis Ths compounds show that tagting ULK1 and ULK2 could b bnficial fo canc tatmnt Ou latst wok on oth ULK family mmbs shows an incasing complxity in thi dual ols in dvlopmnt and in canc

Acknowldgmnts SCHOOL OF MEDICINE, STONY BROOK UNIVERSITY ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI OFFICE OF THE VICE PRESIDENT FOR RESEARCH, STONY BROOK UNIVERSITY DEPARTMENT OF CHEMISTRY, STONY BROOK

8 Acknowldgmnts SCHOOL OF MEDICINE, STONY BROOK UNIVERSITY ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI OFFICE OF THE VICE PRESIDENT FOR RESEARCH, STONY BROOK UNIVERSITY DEPARTMENT OF CHEMISTRY, STONY BROOK UNIVERSITY CHEM-MASTER INTERNATIONAL INC TARGAGENIX INC CHEMBIO DIAGNOSTICS SYSTEMS INC HOFFMANN & BARON LLP AVANTI BIOSCIENCES INC 717 Chmisty Building Stony Book Univsity Stony Book, NY Phon: (631) Fax: (631) wwwstonybookdu/icbdd Stony Book Univsity/SUNY is an affimativ action, qual oppotunity ducato and mploy

Content Skills Assessments Lessons. Pull Ups with progressions. Stick Curl Ups with progressions. Push Ups with progressions

Content Skills Assessments Lessons. Pull Ups with progressions. Stick Curl Ups with progressions. Push Ups with progressions Tach: CORE Physical Education Gad 4 Ya: 2012-13 Cous: Physical Education Gad 4 Month: All Months S p t m b O c t o b P Class Wam Up Activity Essntial Qustions What a th bnfits of bing physically fit? How