Dr. Vivek Rangnekar's Laboratory


The laboratory of Vivek M. Rangnekar, PhD, studies the molecular cross-talk between oncogenes and tumor suppressor genes, in an effort to tilt the balance in favor of tumor suppressor function. The strategy is to utilize the inherent strengths of the tumor against itself, to specifically target cell survival mechanisms that are common to diverse cancers, while leaving the normal host cells unharmed. The multi-faceted tumor suppressor protein Par-4/PAWR, originally identified by Dr. Rangnekar in 1993, serves as a paradigm for such studies. Interestingly, up-regulation of Par-4 protein induces apoptotic death specifically in cancer cells, and its absence leads to tumor growth. Par-4 induces apoptosis intracellularly acting in the cytoplasm or nucleus, or extracellularly via its cell surface receptor GRP78. Dr. Rangnekar’s team is now studying novel Par-4 secretagogues that can cause elevated secretion of Par-4 for inhibition of primary and metastatic tumors.

Chart outlining research

Dr. William St. Clair's Laboratory

The long-term goal of my research program is to translate basic biological knowledge into a practical application for improving the control of cancer and quality of life for cancer patients. My laboratory is addressing the fundamental mechanisms by which radiation-induced cytokine production contributes to normal tissue injury and cancer progression in order to develop novel strategies for intervention, to identify mechanistic based novel therapeutic agents and translate them into clinical applications.

The first goal is to determine the mechanism by which RelB modulates radiation responses in normal and cancer cells and test the concept that selective inhibition of RelB can lead to selective enhancement of cancer cell killing by radiation while sparing normal tissue in an experimental therapeutic setting. This project includes in-depth mechanistic studies in cultured cells and animal models that will be translated to clinical settings. Evidence from this project indicates that overexpression of RelB results in accelerated tumor growth and reduction of RelB suppresses tumor growth. Remarkably expression of RelB in prostate cancer cells leads to decreased PSA production, but increased levels of IL-8. Currently we are attempting to determine if serum IL-8 level is a predictive marker of prostate cancer response to radiation treatment using samples from prostate cancer patients.

An extension of this project is to identify novel therapeutic approaches aimed at increasing cancer therapy efficacy without increasing normal tissue toxicity. Because, elevated oxidative stress and aberrant redox homeostasis are more frequently observed in cancer cells than in their normal counterparts, we propose that the differences in redox homeostasis between normal and cancer cells create a therapeutic opportunity for pushing cancer cells toward death while protecting normal tissue. Our recent studies have identified a previously unrecognized differential effect of parthenolide.