Research: Center of Excellence for Infectious Diseases
Manjunath Swamy, M.D.
Prof. Biomedical Sciences and Co-Director of the Center of Excellence for Infectious Diseases
Department of Biomedical Sciences
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.
- Ongoing Projects
Selected Recent publications
1. Chunting Ye, Jang-Gi Choi, Sojan Abraham, Haoquan Wu, Dolores Diaz, Daniel Terreros, Premlata Shankar, and N. Manjunath. Human macrophage and dendritic cell-specific silencing of high-mobility group protein B1 ameliorates sepsis in a humanized mouse model. Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21052-7. doi: 10.1073/pnas.1216195109. Epub 2012 Dec 3.
2. Haoquan Wu, Hongming Ma, Chunting Ye, Danielle Ramirez, Shuiping Chen, Jessica Montoya, Premlata Shankar, Xiaozhong A. Wang, N. Manjunath. Improved siRNA/shRNA Functionality by Mismatched Duplex. PLoS One. 2011;6(12):e28580. Epub 2011 Dec 9.
3. Chahar HS, Chen S, Manjunath N. P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication. Virology. 2013 Feb 5;436(1):1-7. doi: 10.1016/j.virol.2012.09.041. Epub 2012 Oct 24.
4. Shuiping Chen, Harendra S. Chahar, Sojan Abraham, Haoquan Wu, Theodore C. Pierson, Xiaozhong A. Wang, N. Manjunath. Ago-2-mediated slicer activity is essential for anti-flaviviral efficacy of RNAi. PLoS One. 2011;6(11):e27551. Epub 2011 Nov 10.
5. Chunting Ye, Sojan Abraham, Haoquan Wu, Premlata Shankar, Manjunath N. Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis. PLoS One. 2011 Mar 15;6(3):e17889.
6. Garg H, Joshi A, Ye C, Shankar P, Manjunath N. Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Virol J. 2011 Jan 21;8:34. doi: 10.1186/1743-422X-8-34.
7. Sang-Soo Kim, Chunting Ye, Priti Kumar, Isaac Chiu, Sandesh Subramanya, Haoquan Wu, Premlata Shankar and N Manjunath. Targeted Delivery of siRNA to Macrophages for Anti-inflammatory Treatment. Mol Ther. 2010 May;18(5):993-1001.
8. Wu H, Neilson J, Manjunath N. MicroRNA cloning from cells of the immune system. Methods Mol Biol. 2010;667:67-77. doi: 10.1007/978-1-60761-811-9_5.
9. Priti Kumar, Hong-Seok Ban, Sang-Soo Kim, Haoquan Wu, Todd Pearson, Dale Greiner, Amale Laouar, Jiahong Yao, Viraga Haridas, Katsuyoshi Habiro, Yong-Guang Yang, et al, T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice. Cell. 2008 Aug 22;134(4):577-86.
10. Priti Kumar, Haoquan Wu, Jodi L. McBride, Kyeong-Eun Jung, Moon Hee Kim, Beverly L. Davidson, Sang Kyung Lee, Premlata Shankar & N. Manjunath. Transvascular delivery of small interfering RNA to the central nervous system. Nature. 2007 Jul 5; 448(7149):39-43.
11. Kumar P, Lee SK, Shankar P, Manjunath N. A single siRNA suppresses fatal encephalitis induced by two different flaviviruses. PLoS Med. 2006 Apr;3(4):e96. Epub 2006 Feb 14.
12. Laouar A, Haridas V, Vargas D, Zhinan X, Chaplin D, van Lier RA, Manjunath N. CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa. Nat Immunol. 2005 Jul;6(7):698-706. Epub 2005 Jun 5.
Chunting Ye, Ph.D.
Harendra Chahar, Ph.D.
Post Doctoral Research Associate
Hua Guo, Ph.D.
Post Doctoral Research Associate