Professor and Chair
Postdoctoral Training: 1981-1983, McMaster University Med. Ctr., Hamilton, Canada
1983-1986, University of Kentucky Med. Ctr., Lexington, KY
1970, Bangalore University, India
1974, Karnatak University, Dharwar, India
1981, Defense R. & D. Establishment, Gwalior, India
Office: (803) 216-3404
Fax: (803) 216-3413
The primary research interests of my lab include Cancer Immunology and Immunotherapy, Biodefense, Immunopharmacology, Immunotoxicology, and Complementary and Alternative Medicine. Currently, we are pursuing research in the following specific areas.
- Cancer Immunology and Immunotherapy:
Interleukin-2 (IL-2) has been shown to be effective in the treatment of certain types of cancer including human melanomas and renal cell carcinomas. However, IL-2 therapy is accompanied by severe life-threatening toxicity characterized by endothelial cell injury leading to vascular leak syndrome (VLS). We are interested in reducing the toxicity associated with such therapy by preventing the interaction of a molecule known as CD44 present on cytotoxic lymphocytes with their ligands found on endothelial cells. Our studies are aimed at addressing the role of various CD44 isoforms present on the lymphocytes that may be involved in endothelial cell injury and tumor rejection. (Supported by NIH grants R01 AI053703 and R01 HL058641).
We are also working on another project which involves studying the cellular and molecular mechanisms by which bryostatin-1, a pharmacological agent used in the treatment of cancer, can induce immunomodulation and thereby cause rejection of tumors. Our initial studies have demonstrated that bryostatin-1 induces dendritic cell maturation by serving as a TLR4 ligand. Further studies are underway to examine the downstream signaling pathway following bryostatin ligation.
Yet another area of our research is to examine the role of immune cells including NK, NKT and T cells involved in acute lung injury induced by staphylococcal enterotoxin which is a select agent designated by the Centers for Disease Control and US Department of Agriculture. Furthermore, studies will be carried out to develop strategies to block the toxicity. (Supported by NIH grant R01 058300)
In a collaborative study, we also wish to address the downstream signaling mechanisms involved in induction of apoptosis of T cells and dendritic cells by delta9-tetrahydrocannabinol (THC), the active ingredient in marijuana. We are specifically determining whether the death-receptor pathway or the mitochondrial pathway or both are involved in apoptosis. Attempts are also underway to determine whether other natural or synthetic selective cannabinoid receptor agonists could be used in the treatment of diseases such as cancer and autoimmunity. (Supported by NIH grant R01 DA016545).
Studies from our lab are also aimed at delineating the mechanism by which environmental pollutants such as TCDD (dioxin) and other endocrine disruptors cause immunotoxic effects. We have demonstrated that Fas+ mice are more sensitive than Fas- mice in their susceptibility to TCDD-mediated thymic atrophy suggesting that Fas may be a molecule involved in TCDD-induced apoptosis of thymocytes. Studies are in progress to determine the role of AhR in dioxin-induced upregulation of Fas and Fas ligand. We are also addressing the immunotoxic effects induced by exposure to TCDD during pregnancy in both the mothers and the fetuses. Such alterations in the immune system could lead to susceptibility to infections as well as development of autoimmunity, allergies and cancer (Supported by NIH grant R01 ES009098).
Lastly, we are pursuing research on one of the 3 projects of an NIH-funded Center for Complementary and Alternative Medicine on Autimmune and Inflammatory Diseases (P01 AT003961) grant awarded to Dr. Prakash Nagarkatti. We are studying the mode of action of cannabidiol, which is a nonpsychotropic ingredient found in hemp seed and oil, in the treatment of an experimental model of autoimmune hepatitis. The other 2 projects deal with studies on the effect of resveratrol, an ingredient found in red grape seed and skin in the treatment of experimental multiple sclerosis and the mechanisms underlying the role of American ginseng in the prevention and treatment of colitis.