Susan Ceryak, Ph.D.Associate Research ProfessorDepartments of Pharmacology & Physiology and of Medicine

Tel: 202 994 3896phmsmc@gwumc.eduSurvival signaling and carcinogenesisJanuary 10, 2007NIH/NCI R01CA107972McCormick Pilot Grant

Can we alter cell fate after genotoxin exposure by manipulating survival pathways?Do survivors of genotoxin exposure exhibit altered survival pathways?Overall objective: to elucidate the coordinate signaling events mediating cell fate determination and survival after genotoxic insultNIH/NCI R01CA107972McCormick Pilot Grant

BJ-hTERTDeath Resistant DP 5.14genotoxingenotoxinSubcloned from survivors of genotoxin exposureAltered survival signalingParental (Death-sensitive)Death-resistantHuman diploid fibroblastsLaura Beaver

After genotoxin exposure in death resistant cells:Mitochondrial HK II association is enhanced Mitochondrial reticular network is alteredLaura BeaverTherese LizardoKristen WrightAshley LarrimoreAKT is upregulatedVDAC is NOT upregulated

MitochondrionHypothetical model for AKT-mediated death resistance

Cr(VI)+ PTP inhibitor (SOV)Is AKT necessary for SOV effect? siRNA/ dn AKT studies? What other pathways are involved in SOV effect? (gene array)What is the mechanism of cell cycle checkpoint bypass?

Dongsoon Bae Tura CamilliGina Chun Kristen Wright