The primary research interests of Govindarajan Rajagopalan, Ph.D., are in understanding the immunopathogenesis of diseases caused by the two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, with particular reference to their superantigen (SAg) exotoxins.
Delineating the immunopathogenesis of type 1 diabetes is the other area of interest. Dr. Rajagopalan's laboratory uses humanized transgenic mice expressing human leukocyte antigens (HLA) for these studies. As these transgenic mice closely reproduce the human diseases, they have been valuable tools in understanding the disease process very precisely.
- Delineate the roles of SAgs in the pathogenesis of various acute and chronic diseases caused by S. aureus and S. pyogenes using HLA class II transgenic mice
- Delineate the roles of SAgs produced by S. aureus biofilms
- Investigate the roles of SAgs in the pathogenesis of autoimmune diseases (such as lupus) and asthma
- Evaluate various therapeutic strategies for the treatment of diseases involving bacterial SAgs
- Investigate the mechanisms by which certain HLA molecules predispose to type 1 diabetes
- Understanding the mechanisms behind the immune-mediated destruction of beta cells by transferring T and B cells isolated from human type 1 diabetes patients into immunodeficient humanized mice
- Investigate the mechanisms by which dietary gluten can cause type 1 diabetes, particularly whether dietary gluten could alter the intestinal microbiota
Significance to patient care
Staphylococcus aureus and Streptococcus pyogenes cause a spectrum of human diseases, with many of them being life-threatening. Several toxins produced by these bacteria contribute to the pathogenesis. Among them, the SAgs are particularly important because they are the most potent activators of the immune system. Nonetheless, the contribution of these toxins to bacterial pathogenesis is not precisely understood.
As HLA class II transgenic mice mount a human-like response to SAgs, they are ideally suited to delineate the roles of SAgs in various diseases, as well as in the evaluation of effective countermeasures against these toxins that will be ultimately used in humans.
Type 1 diabetes is an autoimmune disease afflicting the beta cells of islets of Langerhans. While the root cause of type 1 diabetes is not understood, expression of certain HLA alleles, particularly HLA-DQ8, HLA-DQ2, HLA-DR4 and HLA-DR3, increases the risk of type 1 diabetes. Lessons learned from humanized transgenic mice expressing these molecules would have direct implications in the prevention and cure of type 1 diabetes.
- Junior Faculty Travel Award, Annual Meeting of the American Association of Immunologists, 2012
- Junior Faculty Travel Award, Annual Meeting of the American Association of Immunologists, 2009
- Young Investigator Antibacterial Research Award, Advancing Science Through Pfizer Investigator Research Exchange (ASPIRE), 2009
- Junior Faculty Travel Award, Annual Meeting of the American Association of Immunologists, 2007
- FOCIS Award, 4th Annual Trainee Satellite Symposium, FOCIS, 2007
- FOCIS Award, 3rd Annual Trainee Satellite Symposium, FOCIS, 2006
- Postdoctoral Fellowship, Juvenile Diabetes Research Foundation, 2004-2006
- Postdoctoral Travel Award, Juvenile Diabetes Research Foundation, 2005
- Federation of Clinical Immunology Societies (FOCIS) Centers of Excellence Trainee Satellite Symposium Travel Fellowship, 12th International Congress of Immunology and 4th Annual Conference of FOCIS, 2004