Chinnaswamy Jagannath, Ph.D.
1984, University of Madras
The University of Texas Health Science Center at Houston
Medical School
Department of Pathology and Laboratory Medicine
|
Chinnaswamy Jagannath, Ph.D. 1984, University of Madras The University of Texas Health Science Center at Houston |
Research Interests:
The major focus of my laboratory is on vaccine development for tuberculosis. Tuberculosis is the leading cause of death due to infections in the world today and we are working on newer strategies to develop vaccines. We developed a novel gene knockout vaccine from Mycobacterium tuberculosis (Mtb) that protects mice better than BCG (Infection& Immunity, 2000, 2004). We propose to develop this ultimately into a candidate vaccine for humans. Although BCG is used a vaccine against tuberculosis in man, it does not offer long term protection. Parameters for long term immunity are uncertain. However, a key defect in development of better vaccine effect is that both BCG and wild type Mtb inhibit phagosome maturation, lysosomal degradation and processing of antigens through MHC pathway so that effective T cell responses are probably not induced. We have therefore developed novel hypotheses and mechanisms to address this issue.
Antigen processing and induction of T cell responses: We are investigating the ability of candidate Mtb vaccine strains to undergo phagosome maturation within macrophages and dendritic cells (DCs) and get processed in a manner that an efficient T cell response is induced. We hope to induce long term memory by inducing the right type of effector T cell responses. Central to our efforts are our research on: a) the bactericidal function of macrophages that involves phagocyte oxidase and inducible nitric oxide synthase, b) the role of Cathepsin proteases of macrophages and DCs on mycobacterial degradation & the role of cathepsins in loading peptides to MHC complex before presentation to T cells, and c) the induction of long term immunity in mice. The role of DCs and macrophages in priming and expanding the three pathways of T-cell function (Th1, Th2 and Th3) is also a major area of thrust. We use various strains of mice, gene knockout Mtb strains, various cell culture models and the mouse model of tuberculosis to analyze these events. We assay cellular markers using flow cytometry, analyze cellular signaling cascades with immunochemistry and PCR and analyze intracellular trafficking of pathogens with laser confocal microscopy. A tutorial in my laboratory will therefore provide an insight into the immunity mechanisms & the pathogenesis of intracellular infections as exemplified by tuberculosis.
Selected Publications:
Rachel Moulton, Mary Anne Connelly,Amanda K. Smith, Devin R.Lindsey, Rick A.Wetsel, David L.Haviland, Robert L Hunter. Jr. & C. Jagannath. 2007. Complement C5a anaphylatoxin is an innate determinant of dendritic cell mediated Th1 immunity during Mycobacterium bovis BCG infection in mice. J.Leucocyte Biology, 2007:82:956-967.
Xu,Y, C.Jagannath and Tony Eissa. 2007.Toll-like receptor 4 is a sensor for autophagy associated with innate immunity"(IM-D-06-00812R2), Immunity 2007 : 27; 135-144.
Szeliga J, Daniel DS, Yang CH, Sever-Chroneos Z, Jagannath C, Chroneos ZC. Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis. Tuberculosis (Edinb). 2008: 88:7-2.
Katti, MK, Dai, G, Daniel, S, Singh, Jagannath. C. 2008. The ΔfbpA vaccine derived from Mycobacterium tuberculosis H37Rv has an enhanced susceptibility to intracellular antimicrobial oxidants, undergoes limited phagosome maturation and activates murine macrophages and dendritic cells. Cellular Microbiology 2008, 10:1286-303
Additional Publications
Program Affiliations:
Program
in Immunology
Program in Molecular Pathology