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Susan Ceryak, Ph.D. Associate Research Professor

Survival signaling and carcinogenesis. Susan Ceryak, Ph.D. Associate Research Professor Departments of Pharmacology & Physiology and of Medicine Tel: 202 994 3896 phmsmc@gwumc.edu. NIH/NCI R01CA107972 McCormick Pilot Grant. January 10, 2007.

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Susan Ceryak, Ph.D. Associate Research Professor

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  1. Survival signaling and carcinogenesis Susan Ceryak, Ph.D. Associate Research Professor Departments of Pharmacology & Physiology and of Medicine Tel: 202 994 3896 phmsmc@gwumc.edu NIH/NCI R01CA107972 McCormick Pilot Grant January 10, 2007

  2. Overall objective: to elucidate the coordinate signaling events mediating cell fate determination and survival after genotoxic insult Genotoxin Transient Checkpoint Arrest “Terminal” Apoptosis Growth Arrest Clonogenic Survival Do survivors of genotoxin exposure exhibit altered survival pathways? Can we alter cell fate after genotoxin exposure by manipulating survival pathways? NIH/NCI R01CA107972 McCormick Pilot Grant

  3. Human diploid fibroblasts BJ-hTERT genotoxin Parental (Death-sensitive) Death Resistant DP 5.14 genotoxin Subcloned from survivors of genotoxin exposure Altered survival signaling Death-resistant Laura Beaver

  4. After genotoxin exposure in death resistant cells: HeLa Parental Death-resistant m c m c m c m c Cr(VI), um 0 6 0 6 mito/cyto 0.7 0.4 2.9 1.1 Death-resistant Parental AKT is upregulated VDAC is NOT upregulated Mitochondrial HK II association is enhanced Mitochondrial reticular network is altered Laura Beaver Therese Lizardo Kristen Wright Ashley Larrimore

  5. ser473 P thr308 P AKT GSK3 HK HK thr51 P VDAC VDAC Hypothetical model for AKT-mediated death resistance Mitochondrion

  6. Cr(VI) + PTP inhibitor (SOV) clonogenic lethality  cell cycle checkpoint arrest  apoptosis no effect  DNA adducts no effect  mutations at HPRT locus   p and tot AKT and AKT activity 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 Camilli Gina Chun Kristen Wright

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