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Chinnaswamy Jagannath, Ph.D. Address and Contact:
My Profile http://dpalm/faculty/bios/jagannath/jagannath.html Office: MSB 2.200 |
Research Interests:
The major focus of my laboratory is on the biology of Mycobacterium tuberculosis (MTB) which parasitizes macrophages. We are trying to understand the protective and pathologic mechanisms in tuberculosis by looking at the ability of macrophages to phagocytose, kill, digest and present antigens besides secreting mediators that amplify the magnitude of immune responses using novel methods of cell culture, mouse models and knock out mutants of MTB.
Macrophage Biology: The primary thrust is to understand macrophage activation phenomenon responsible for killing mycobacteria. We developed a novel in vitro long term model of macrophage granuloma using THP1 macrophages that is anticipated to enhance our understanding of monocyte differentiation. We identified a novel regulatory mechanism of reactive oxygen species synthesis via Complement C5a anaphylatoxin using C5 KO macrophages. We also developed sensitive methods to detect NO response in human and murine macrophages. Recent studies have identified novel probes to monitor phagosome-lysosome fusion phenomenon. Using a combination of free radical assay, immuno-cytochemistry, electron microscopy and confocal fluorescent microscopy we are now defining the molecular basis of events that co-ordinate these mycobactericidal mechanisms within human and murine macrophages.
Novel mouse models for tuberculosis: We developed acute, sub-acute, chronic and reactivation tuberculosis models to understand the pathogenesis of tuberculosis. We described a novel mouse model in which the granuloma formation that is critical for the control of lung tuberculosis is defective and is regulated by chemokines through a novel pathway involving C5a and TNF alpha. Research on the relationships between chemokines, cytokines and granuloma formation and function is a second thrust area.
Vaccine Research: Vaccine research in TB has received a boost since BCG vaccine does not adequately protect against adult tuberculosis. We characterized a novel mutant of MTB (A-) that has a vaccine potential. Using various strains of mice, ex vivo cultures of macrophages and lymphocytes we are investigating the basis of antigen presentation, cytotoxic immunity and memory responses in order to propose A- vaccine as a novel vaccine for tuberculosis.
Recent Publications
Jagannath
C, Wetsel, RA, and Hunter RL. Reduced bactericidal capacity of Complement C5
deficient macrophages is due to reduced synthesis as well as delivery of
reactive oxygen species to mycobacterial phagosomes. Tuberculosis: Molecular
Mechanisms during the Post genome Era, Keystone Symposia, Jan
24-29th, 2001, Taos, NM.USA (Abstract)
Hunter
RL, Chan
D and
Jagannath C. A novel method of measuring phagosome-lysosome fusion, respiratory
burst and intracellular killing of mycobacteria in macrophages. Tuberculosis:
Molecular Mechanisms during the Post genome Era, Keystone Symposia, Jan
24-29th, 2001, Taos, NM.USA (Abstract).
Jagannath
C, Hoffmann H,
Sepulveda S, Actor JK, Wetsel RA and Hunter RL. Hyper-susceptibility of A/J mice
to tuberculosis is in part due to a deficiency in the fifth Complement component
(C5) Scandinavian J. Immunology. 2000:
52:369-379.
Actor JK, Breij E, Hoffmann H, Sepulveda E, Wetsel RA and
Hunter RL, Jagannath C. A role for Complement C5 in organisms containment and
granulomatous response during murine tuberculosis in mice. Scandinavian J. Immunology (2001) in
press.
Armitige L, Jagannath C,
Wanger A, and Norris SJ. Disruption of the genes encoding antigen 85A and
antigen 85B of Mycobacterium tuberculosis H37Rv. Infection &
Immunity 68, 767-778,2000.
Jagannath C, Sepulveda E,
Actor JK, Luxem F, Emanuele RM, and Hunter RL. Effect of poloxamer CRL1072 on
drug uptake and nitric oxide mediated killing of Mycobacterim avium by
macrophages. Immunopharmacology,
2000: 48;185-197.
Jagannath C, Actor JK, and Hunter. RL. Induction of Nitric Oxide in human monocytes and monocyte derived cell lines. Nitric Oxide: Biology and Chemistry 2:174-186,1998.
