Primary Appointment

Dual/Joint/Adjunct Appointment

Research Interests Angiogenesis and anti-angiogenic agents, Tumor cell migration and invasion, Apoptotic cell recognition mechanisms, Intracellular calcium signaling during apoptosis and necrosis.

 B.     Ceramide homeostasis as a regulator of chemo-resistance and metastatic potential. Studies from several laboratories have suggested that resistance to apoptosis is associated with the transtion of primary tumors to an invasive, metastatic phenotype. It is however not clear whether acquisition of resistance is a prerequisite towards metastatic progression of the disease. The mechanisms critical to the transition of cancers from a low-metastatic to a high metastatic phenotype are also not clear. Research over the past several years has demonstrated a direct correlation between elevated levels of the sphingolipid, ceramide, and commitment of cells to apoptosis. Interestingly, ceramide-derived lipids like sphingosine-1-phosphate, sphingomyelin and gangliosides promote cell survival, migration and proliferation, processes that are central to invasion and metastasis. Indeed, recent studies in melanoma and breast cancer revealed an association between expression of proteins regulating sphingolipid metabolism and signaling, and, the propensity to metastasize. This research is currently being developed on the concept that alerted regulation of sphingolipid metabolism and signaling is a crucial determinant of cancer development and progression. It is further hypothesized that resistance to apoptosis in ovarian cancer is an inadvertent and inevitable consequence of depletion in the pro-apoptotic ceramide pools by its metabolism to pro-metastatic signaling molecules that promote survival, proliferation, migration and differentiation. The objective of this research is to use various cancer models to evaluate the potential correlation between the various stages of cancer progression and, differential expression of enzymes/proteins that regulate sphingolipid metabolism and signaling, with the ultimate goal of developing these as biomarkers in early diagnosis.

 C.    Regulation of intracellular calcium homeostasis during programmed cell death. Resistance to apoptosis is one of the major obstacles in the treatment and eradication of cancer. Hence, understanding the mechanisms for resistance is crucial for development of improved therapeutic strategies to combat the disease. Studies from many laboratories have indicated a close interrelationship between cellular metabolism and intracellular Ca²⁺ homeostasis. Since autophagy and apoptotic response are invariably linked to cellular metabolism and cytosolic Ca²⁺, it is likely that both resistance to apoptosis and, induction of autophagy might provide a means for protection of metastasizing tumor cells from stress, cytokine and nutrient-deprivation induced apoptosis in a new tissue microenvironment. This research project is currently focused on the role of the ER and the mitochondria in regulating cytosolic Ca²⁺ and phosphatidylserine externalization (anti-inflammatory phagocyte signal) during tumor cell apoptosis.

Administrative Appointments/Responsibilities

Last updated: 9/8/2009