Investigators

Summary

The overarching goal of my research is to understand the cellular mechanisms that lead to genome instability, focusing on regions of the genome especially vulnerable to harmful environmental exposures. I particularly focus on defining the roles of ADP-Ribose transferase enzymes (ARTs/PARPs) in orchestrating the maintenance of both telomere and centromere integrity when exposed to chronic oxidative stress, a leading cause of tumorigenesis. DNA-dependent PARPs are key components of the DNA damage response and as such, are primary targets in cancer therapies. However, little is known on how PARPs operate at telomeres and centromeres upon oxidative DNA damage induction and how PARP inhibitors affect non-diseased cells in cancer patients. My laboratory’s mission is to therefore 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 which will ultimately reveal fruitful in a translational and clinical setting to provide therapeutic alternatives. Beside support from the UPMC Hillman Cancer Center start-up funds, my laboratory is currently funded by (i) an R00 (NCE; NIEHS) to investigate the roles of PARP1 and PARP2 in the repair of oxidative DNA damage and the resolution of G quadruplex structures at telomeres as well their role in regulating telomerase enzyme; and (ii) an MIRA R35 (NIGMS) that investigates the impact of oxidative stress on centromere integrity and cell viability as well the specific roles of PARP enzymes in preserving their integrity. Pending R01 grant proposes to investigate R-loop structures as novel substrates for PARP1 and focuses on uncovering PARP1 function in their resolution.