Description of Research:
The major focus of our lab is to understand the molecular mechanisms that lead to cellular transformation, ultimately leading to cancer. We study the role of various oncogenes and tumor suppressors that regulate cell cycle progression, particularly during mitosis. We are looking at the impact of various proteins that affect the regulation of spindle assembly checkpoint (SAC) during mitosis. We have been predominantly using the small T antigen of Polyoma virus as a model to study the impact of these proteins on mitotic regulation. Expression of small T antigen is known to cause major mitotic abnormalities in mammalian cells like abnormal spindles, lack of chromosomal congression, aneuploidy etc, which lead to mitotic arrest, followed by apoptosis in mammalian cells. We use various genetic, biochemical, molecular and cell biology approaches to identify the cellular proteins that allow the “abnormal cells” to repair such anomalies and overcome apoptosis. These approaches will possibly help us understand the role of such proteins in enabling cancer cells to overcome cell death induced by internal cellular signaling as well as by anticancer drugs and develop resistance against them. Some of the prominent candidates that we are studying are Mastl, DBC1, UNC5B, PCTAIRE1 and lipin1. In addition, our lab also studies the role of kinases and phosphatases in the regulation of cell division (particularly mitosis), apoptosis/ cell survival and resistance against cell death during tumorigenesis.