Annapoorna Venkatachalam

Thesis Lab

Scott H. Kaufmann, MD, PhD.

Research Project

Previously, Dr. Kaufmanns lab has investigated the use of Poly(ADP- ribose) polymerase inhibitors (Parpi) in the management of HR deficient ovarian cancer and also elucidated the mechanism underlying the synthetic lethality observed. Several studies have successfully shown that a therapeutic window could be achieved with PARPi agents and additional agents that target the DNA damage response in HR proficient and HR deficient background. Recently, it has been demonstrated that BRCA1/BRCA2-defective tumors can exhibit resistance to Parpi alone or in combination with these targeted therapies.

The goal of my thesis project is to investigate the underlying mechanism of resistance to PARPi combination therapies in ovarian cancer and to evaluate them in terms of predictors of Parpi response.

For this purpose, I will be using shRNA based genome wide screening to identify targets associated with the resistance phenotype. Further, I will be performing bioassays to validate their functional significance and investigate additional targeting strategies to overcome drug resistance.

July 26, 2017