- Singh CR, Pearl Bakhru Arshad Khan, Qing Bo LI and C.Jagannath. Nicastrin and related components of γ-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC-II dependent priming of T cells. Journal Immunology: Cutting Edge, 2011.
- Estrella JL, Kan-Sutton C, Gong X, Rajagopalan M, Lewis DE, Hunter RL, Eissa NT, Jagannath C. A Novel in vitro Human Macrophage Model to Study the Persistence of Mycobacterium tuberculosis Using Vitamin D(3) and Retinoic Acid Activated THP-1 Macrophages. Front Microbiol. 2011;2:67.
- Li Q, Singh CR, Ma S, Price ND, Jagannath C.Label-free proteomics and systems biology analysis of mycobacterial phagosomes in dendritic cells and macrophages. J Proteome Res. 2011: 10(5):2425-39.
- Rao PK, Singh CR, Jagannath C, Li Q. A systems biology approach to study the phagosomal proteome modulated by mycobacterial infections. Int J Clin Exp Med. 2009 ;2(3):233-47.
- Chroneous Z and C.Jagannath. The role of GM-CSF during pathogenesis of tuberculosis. Book Chapter In: Tuberculosis and Mycobacterium tuberculosis. INTECH (Online, 2011).
Chinnaswamy Jagannath, PhD
Pathology & Laboratory Medicine
(713) 500 - 5353
Vaccine development for tuberculosis
The major focus of my research is on vaccine development for tuberculosis through improving BCG vaccine and introducing novel M.tuberculosis derived vaccines. Tuberculosis is the leading cause of death due to infections in the world today. We initially developed a novel gene knockout vaccine from Mycobacterium tuberculosis (Mtb) that protects mice better than BCG. We propose to develop this ultimately into a novel much better 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 not induced. It should be noted a more effective BCG vaccine can carry multiple epitopes to immunize men and women against tuberculosis, HIV, malaria and other infections. Genetically improved BCG is therefore immensely useful to prevent infections in mankind at a global level. We discovered novel mechanisms to accomplish this task (see News). We are investigating the ability of candidate Mtb and BCG derived novel 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 T cell responses. Current research focus is on: a) Proteomics to dissect pathogenesis of mycobacteria in APCs, b) Toll-like receptor (TLR) mediated signaling of T cells in mice and humans, c) Effector and memory T cell responses to vaccines using mice. We assay cellular markers of T cells m macrophages and DCs 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 vaccine mediated immunity mechanisms involving T cells, macrophages and DCs & TLR mediated signaling to enhance vaccines.
Jagannath Laboratory- STUDENT AWARDS