Research: Center of Excellence for Infectious Diseases

West Nile and St. Louis encephalitis viruses can cause devastating brain infections in humans and there is no treatment or vaccine for these infections. The Swamy lab is testing the therapeutic applicability of siRNAs to prevent and cure these infections. They have identified several RNAi targets that can provide near complete protection against the fatal disease in animal models. By selecting certain regions of the viral genome that are conserved across species as targets, they have also shown that siRNAs can be developed as broad-spectrum antiviral agents to suppress multiple different, but related viruses.

Since infection of brain cells is the cause for the severe disease, the Swamy lab is also interested in developing methods to achieve targeted delivery of siRNA to brain cells. They have developed a novel method using a short peptide that binds to a brain cell surface protein to deliver siRNAs to brain after intravenous injection.

The Swamy lab is also studying how the endogenously encoded miRNAs regulate the activation and differentiation of antigen-specific T cells. They have shown that although 100s of miRNAs are expressed in na�ve T cells, only a handful of these predominate. Interestingly, most of these miRNAs are turned off after activation and this decrease in miRNAs expression inversely correlates with highly increased gene expression in activated cells. These results indicate that relief from miRNA-mediated repression is essential to increase gene expression after T cell activation.

The Swamy lab is also interested in mucosal immunity. Many pathogens enter the body through mucosal sites and the immune response at mucosal sites differs qualitatively and quantitatively from that at peripheral tissues. The Swamy lab has identified a novel type of antigen-presenting cell in the intestinal mucosa that expresses a costimulatory molecule called CD70. Interaction of CD70 with its ligand CD27 expressed by T cells appears to be essential for T cell response in the gut mucosa and blocking this interaction using CD70 antibody can reduce the mucosal response. Since aberrant activation of gut mucosal T cells is the cause of inflammatory bowel disease in humans, we are testing if CD70 blockade can inhibit IBD in experimental animal models.

Dr. Swamy obtained his M.D. degree from the All India Institute of Medical Sciences, New Delhi, India and received postdoctoral training at the Tufts-New England Medical Center. He was as an investigator at the Immune Disease Institute, Harvard Medical School before joining the TTUHSC.