Faculty and Staff
|Title:||SmartState Endowed Chair of Center for Cancer Drug Discovery
Carolina Distinguished Professor; Chair, Dept. of Pathology, Microbiology and Immunology
|Department:||Pathology, Microbiology, and Immunology
School of Medicine
Pathology, Microbiology & Immunology
1981-1983, McMaster University Med. Ctr., Hamilton, Canada
Research Associate 1983-1986, University of Kentucky Med. Ctr., Lexington, KY
B.S.-- 1970, Bangalore University, India
M.S. -- 1974, Karnatak University, Dharwar, India
Ph.D. -- 1981, Defense R. & D. Establishment, Gwalior, India
I have broad-based research interests in the areas of Inflammation, Cancer Immunology and Immunotherapy, Biodefense, Immunopharmacology, Immunotoxicology, as well as Complementary and Alternative Medicine. Inflammation is the underlying cause of various diseases including cardiovascular, neurodegenerative and autoimmune diseases as well as obesity, aging and cancer. We are mainly using cutting-edge technology including epigenomic and genomic approaches to study various diseases both in experimental models and in patients. Our research also focuses on in silico modeling as well as use of ex vivo cultures for determining cellular and molecular mechanisms. In addition, we are studying yet another novel research area namely the dysbiosis in the microbiome in various tissues. Our lab is supported by several grants from National Institutes of Health (NIH) (R01 AI129788; R01 AT06888; R01 MH094755; P01 AT003961; P20 GM103641). Currently, we are pursuing research in the following specific areas:
- Inflammatory Diseases: We are addressing the epigenetic mechanisms including dysregulation in microRNA expression, DNA methylation and histone modifications underlying induction of disease as well as developing strategies for prevention and
treatment. Furthermore, we are examining the gut, lung and skin microbiota in these
diseases. The diseases include
- Multiple sclerosis and experimental autoimmune encephalomyelitis
- Colitis and colon cancer
- Autoimmune Hepatitis
- Transplant Rejection
- Cancer Biology and Immunotherapy:
We are also developing novel therapeutic agents against cancers including neuroblastomas, melanomas and lymphomas. For the drug discovery studies, we are using a small molecule library of 100,000 compounds to explore the effects on cancer cells as well as immune cells. Furthermore, we are also reducing the toxicity of the cytokine, IL-2 used to treat certain types of cancers such as human melanomas and renal cell carcinomas. This will be accomplished by targeting CD44, a molecule found on immune cells and tumor cells.
Yet another area of our research is to examine the immune mechanisms involved in acute lung injury (ALI) induced by staphylococcal enterotoxin B (SEB) which is a select agent of bioterrorism designated by the Centers for Disease Control. SEB is produced by Staph. aureus which is responsible for hospital-borne infections, causing fever, vascular leak, ALI, acute respiratory distress syndrome, multiple organ failure and may be fatal. Furthermore, studies will be carried out to develop strategies to block the disease. We are also examining the nature of inflammation and cytokines in sepsis patients,
We also wish to address the downstream signaling mechanisms involved in alteration in CD4+ T cell differentiation induced by cannabinoids such as delta9-tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana. We are specifically determining whether cannabinoids mediate immunosuppression in patient abusing the drug, by induction of T regulatory cells and myeloid derived suppressor cells. Attempts are also underway to determine whether other natural or synthetic selective cannabinoid receptor agonists could be used in the treatment of inflammatory diseases and cancer.
Studies from our lab are also aimed at delineating the mechanism by which environmental pollutants such as TCDD (dioxin) as well as estrogens and other endocrine disruptors cause immunotoxic effects. We are examining the transgenerational immunotoxic effects of exposure of both mothers and fetuses to these xenobiotics during pregnancy by assessing epigenetic imprinting. Such alterations in the immune system could lead to susceptibility to infections as well as development of autoimmunity, allergies and cancer later in life (Supported by NIH grant R01 ES009098).
- Post-traumatic Stress Disorder (PTSD):
PTSD may occur following exposure to an extremely stressful event such as combat, assault and violence. Over 1.6 million veterans returning from Iraq and Afghanistan wars are estimated to be suffering from PTSD. We are determining the epigenetic mechanisms underlying immune dysfunction in PTSD.
- Complementary and Alternative Medicine:
Lastly, we are pursuing research on one of the 4 projects of an NIH-funded Center for Complementary and Alternative Medicine on Autoimmune and Inflammatory Diseases (P01 AT003961) grant. In this area, we are studying the mode of action of resveratrol, an ingredient found in red grape seed and skin in the treatment of experimental multiple sclerosis and also the role of indoles such as I3C and DIM found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage and cauliflower in colitis.