Synopsis of Research Program

The primary focus of our laboratory over the years has been in deciphering signaling networks that promote cellular transformation and elucidating mechanisms that endow cancer cells the ability to evade execution. Our focus has been on identifying potential bottlenecks or vulnerabilities that cut across a spectrum of human cancers, and therefore our work includes hematopoietic malignancies as well as solid tumors, in particular, breast, colorectal, lung and pancreatic cancer.  To that end, using a variety of model systems such as oncogene-induced proliferation, expression of apoptosis inhibitory proteins, pharmacological inhibition of key cellular metabolic regulators, receptor and chemotherapy-induced death stimuli, and novel small molecule compounds, we provide evidence that cellular redox metabolism critically impacts cell fate decisions. Of note, across a wide spectrum of cellular redox stress, there emerges a dichotomy of responses in terms of cell survival/proliferation and cell death.  At the lower end of the scale, cell survival and proliferation is favored, while at the other extreme cell execution is the preferred outcome. How these varied levels of stress evoke disparate biological responses with distinct functional outcome(s) and the signaling networks and potential cellular targets that could be amenable to redox modification(s) are the major focus of our ongoing and future investigations.

Research interests

• Regulation of Cell Death Signaling in Cancer Cells

• Reactive Oxygen Species and Cell Fate

• Bcl-2 Family and Mitochondrial Metabolism

• Protein Phosphatase PP2A and Cancer

• Autophagy and Cancer

• Experimental Therapeutics

The brief summary provides a bird’s eye view of the various signaling networks that are the focus of our research program aimed at understanding the intricate relationship between cellular redox state and the processes of carcinogenesis and chemo-resistance. Our group has expertise in a wide array of state-of-the-art cellular/molecular techniques, and experience in working with a variety of human cancers as well as primary cells derived from clinical biopsies. The program has attracted >$10M in extra-mural funding over the years, trained over 25 graduate students and 17 postdoc fellows, and forged close collaboration with basic scientists, clinicians and industry.