Elise Fouquerel

Summary

The overarching goal of my research is to understand the cellular mechanisms that lead to genome instability. We particularly study how exposure to environmental agents can trigger DNA damage and instability at telomeres and centromeres, the most vulnerable regions of the genome. In this context, we focus on defining the roles of the DNA repair proteins ADP-Ribose transferase enzymes (ARTs/PARPs) in orchestrating the maintenance of telomere and centromere integrity. These enzymes are key components of the DNA damage response and are primary targets in cancer therapies. However, resistance to them and deleterious side effects can occur. My laboratory's mission is to develop a research program that will provide a deep mechanistic understanding of genotoxic stress-dependent cancer development and inform the rational design of cancer treatments that will ultimately prove fruitful in a translational and clinical setting to provide therapeutic alternatives. In addition to support from the UPMC Hillman Cancer Center start-up funds, my laboratory is currently funded by (i) an MIRA R35 (NIGMS) that investigates the impact of oxidative stress on centromere integrity and cell viability, as well as the specific roles of PARP enzymes in preserving their integrity. A pending NIH R01 grant proposes to investigate R-loop structures as novel substrates for PARP1 and focuses on uncovering PARP1’s function in their resolution. Finally, a pending American Cancer Society grant proposes to investigate the roles of PARP2 in the response of cancer cells to replication stress and to define PARP2 as a therapeutic target for the treatment of pancreatic cancers.