Chemotherapeutic agents attenuate expression of PIK3CA, a crucial cell survival gene, in p53 dependent manner. This attenuation is abolished in chemoresistant ovarian carcinoma cells which aids the cells to survive against chemotherapeutic agent via escalated PI3K/AKT signalling. My work focuses on investigating the mechanism involved in this differential regulation of PIK3CA in chemoresistant ovarian carcinoma utilizing reporter assays, live cell and in vivo imaging. We find that p53 exerts a unique regulatory mechanism to PIK3CA by altering binding site preference in chemosensitive and in chemoresistant cells. This altered p53 binding is facilitated via various post translational modifications. Currently, I am working on identifying regulator/s of PIK3CA promoter in chemoresistant ovarian carcinoma. Identifying such regulators can be extended in drug discovery research for chemoresistant ovarian carcinoma.
Senior Research Fellow
Bhushan Thakur
Ray Lab