Chinnaswamy Jagannath |
|
University of Texas Health Science Center at Houston Medical School Pathology and Laboratory Medicine Associate ProfessorAppointed: 1997 |
Mailing AddressMSB.2.200 University of Texas - Houston Health Science Center 6431 Fanin Houston, Texas 77030United States | Contact Information |
Qualifications
Ph.D., University of Madras, India, Medical Microbiology, 1984.
M.Sc., Karnatak University (India), Medical Microbiology, 1977.
B.Sc., Bangalore University (India), Chemistry, Botany, Zoology, 1972.
Expertise and Research Interests
The major focus of my laboratory is on host-parasite relationships between Mycobacterium tuberculosis (MTB) and the macrophages. We are trying to understand the protective and pathologic mechanisms in tuberculosis by looking at the ability of macrophagesto 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.
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 (fbpA-) 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 fbpA- vaccine as a novel vaccine candidate for tuberculosis.Additional studies are underway to produce a double KO strain of MTB.
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, 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 in novel animal models is a second thrust area thatis supported by NHLBI, NIH.
Macrophage Biology: The primary thrust here 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 fluorescentmicroscopy we are now defining the molecular basis of events that co-ordinate mycobactericidal mechanisms within human and murine macrophages. Macrophage studies link above two projects.
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 (fbpA-) 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 fbpA- vaccine as a novel vaccine candidate for tuberculosis.Additional studies are underway to produce a double KO strain of MTB.
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, 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 in novel animal models is a second thrust area thatis supported by NHLBI, NIH.
Macrophage Biology: The primary thrust here 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 fluorescentmicroscopy we are now defining the molecular basis of events that co-ordinate mycobactericidal mechanisms within human and murine macrophages. Macrophage studies link above two projects.
Other Expertise
Academic Experience:
Member and Teaching Faculty:Graduate School of Biomedical Sciences, UT; Molecular Pathology Program, UTHSC; Program In Immunology, MD Anderson Cancer Center, UTHSC-Houston.
Reviewer: Molecular Biotechnology;Clin Exp Immunology, Antimicrobial Agents and Chemotherapy; Amer. Rev.resp. Diseases; Journal of Infectious Diseases; Journal of Leucocyte Biology; Int.Journal of Tuberculosis and Lung Disease, Ed Board: Ind.J.medical Microbiology.
Member and Teaching Faculty:Graduate School of Biomedical Sciences, UT; Molecular Pathology Program, UTHSC; Program In Immunology, MD Anderson Cancer Center, UTHSC-Houston.
Reviewer: Molecular Biotechnology;Clin Exp Immunology, Antimicrobial Agents and Chemotherapy; Amer. Rev.resp. Diseases; Journal of Infectious Diseases; Journal of Leucocyte Biology; Int.Journal of Tuberculosis and Lung Disease, Ed Board: Ind.J.medical Microbiology.
Future Research
My future interests are as follows: (a) Develop and characterize attenuated mutants of M.tuberculosis as vaccine candidates (b) Develop newer strategies to optimize and deliver vaccines for tuberculosis and infectious diseases in general c) Optimize newer strategies to develop drugs for treating multi drug resistant tuberculosis.
Industrial Relevance
I have developed an antituberculosis compound to an IND stage. Currently I am working on attenuated and novel vaccination strategies for tuberculosis. I have over 20 years of experience in drug and vaccine development strategies. I can offer consultancy in these matters. I can also accept selected proposals to evaluate new drugs and vaccines against tuberculosis and M.avium disease. I have a state of art BSL3 microbiology and animal facility for this purpose.
Keywords
COS Keywords:
AIDS, Amino Acids, Animal Models, Bacteriology, Chemotherapy, Confocal Microscopy, Immunotherapy, Laboratory Practice Or Procedure, Leprosy, Pathology, Pathophysiology, Peptides, Tuberculosis, Vaccine.Additional Terms:
Animal Models, Chemotherapy, Drug and Vaccine Development, Gene Disrupted Mice, Immunotherapy, Macrophage Modulators, Pathogenesis of Tuberculosis.Languages
(Reading, Writing, Speaking)
English (USA): (Fluent, Fluent, Fluent)
Memberships
American Association for the Advancement of Science
American Society for Microbiology
American Society of Immunologists
Honors and Awards
1998, To date, Member,
CSR, NIH,
Special Emphasis Panel on Infectious Diseases and Microbiology
Ad Hoc Reviewer HIV-RAD panel 2002,
National Institutes of Health (NIH)
Ad Hoc Reviewer: AARR2, 2000,
National Institutes of Health (NIH)
Ad Hoc Reviewer BM1 Panel, 2003,
National Institutes of Health (NIH)
NIH Site Visit Team, National Primate Research Center SA, TX 2004,
National Institutes of Health (NIH)
Grant reviewer,
National Medical Council, Singapore, Grant Reviewer 2004, 2005
Greant reviewer,
Health Research Board, Republic of Ireland, 2006.
Minority mentee-Mentor Award, MARK,2006,
American Association of Immunologists and NIH
Previous Positions
1995-1997, Emory University,
Dept. of Pathology and Lab.Medicine
1991-1993, Research Instructor,
University of Illinois at Chicago,
Department of Medicine,
Mycobacteriology Division
1977-1984, USPHS Leprosy Project. JIPMER, India, Research Officer
1984-1989, National Inst. Communicable Diseases. Ministry of Health, India., Assistant Director
1989-1991, Mycobacterial Diagnostics. ASTRA Research Centre, India, Project Coordinator
1993-1997, Mycobacteriology Division. CytRx Corporation, Norcross, GA, Director
Funding Received
- National Institutes of Health, NHLBI: Principal Investigator, Reactivation tuberculosis in A/J mice, $250,000/ year, Sep 30, 2001 to Aug 30, 2006.
- Centers for Disease Control , USPHS, Atlanta, GA: Principal Investigator, Evaluate the virulence of Mycobacterium tuberculosis using aerosol challenge mouse model, $158,000/year, Oct 1997 to Jul 2000.
- National Institutes of Health, NIA: Principal Investigator, Role of adhesion molecules during reactivation tuberculosis, $50,000, Jan 15, 2001 to Dec 15, 2001.
- NIAID: Principal Investigator, Characterization of an M.tuberculosis derived vaccine, National Institutes of Health, $250,000/year, Jan 1, 2002 to Dec 31, 2006.
- National Institutes of Health (NIH): Molecular Basis of Infectious Disease. T32, No funds, Student st, 2005 to 2013.
- Co-Principal Investigator: CRL-1072 for treatment of Mycobacterium avium, National Institutes of Health (NIH), $137,000 per year, September 1997-September 1999
- Co-Prinicipal Investigator: 'Effects of Surfactants on Tuberculosis of the Lung', National Institutes of Health (NIH), $359,000 per year, September 1995-September 2000
- Principal Investigator: CRL-1072 for treatment of Mycobacterium avium, National Institutes of Health (NIH), $100,000, September 1996-March 1997
Publications
- Copenhaver RH, Sepulveda E, Armitige LY, Actor JK, Wanger A, Norris SJ, Hunter RL, Jagannath C (Dec 2004) A mutant of Mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential., Infection and Immunity, 72 (12), 7084-95
- Douglas T, Daniel DS, Parida BK, Jagannath C, Dhandayuthapani S (Jun 2004) Methionine sulfoxide reductase A (MsrA) deficiency affects the survival of Mycobacterium smegmatis within macrophages, Journal of Bacteriology, 186 (11), 3590-8
- Actor JK, Breij, E., Hoffmann, H, Sepulveda, S, Wetsel, RA, Hunter, R.L. Jr., Jagannath, C., A role for Complement C5 in organism containment and granulomatous response during murine tuberculosis, Scandinavian Journal of Immunology, 53, 464-474, 2001
- Armitige, L., Jagannath, C., Wanger, A., and Norris, S, Disruption of the genes encoding antigen 85A and antigen 85B of Mycobacterium tuberculosis H37Rv, Infection and Immunity, 68, 767-778, 2000
- Watson, VE,Hill, LL, Owen Schaub, LB, Davis, DW, McConkey, DJ, Jagannath, C, Hunter, RL and Actor JK., Apoptosis in Mycobacterium tuberculosis infection in mice exibiting varied immunopathology, Journal of Pathology, 190, 211-220, 2000
- Jagannath, C, Actor, JK, Luxem F and Hunter RL., The effect of CRL-1072 on the drug uptake and nitric oxide mediated killing of Mycobacterium avium in macrophages, Immunopharmacology, 48, 187-197, 01 2000
- Jagannath, C., Hoffmann, H, Sepulveda, S, Actor JK, Wetsel, RA, Hunter, R.L. Jr., Hypersusceptibility of A/J mice to tuberculosis is in part due to a deficiency in the fifth Complement component (C5), Scandinavian Journal of Immunology, 52, 369-379, 2000
- Pai, S., Actor, J.K., Sepulveda, E., Hunter, R.L., and Jagannath. C, Identification of viable and non-viable Mycobacterium tuberculosis in mouse organs by directed RT-PCR for antigen 85B mRNA, Microbial Pathogenesis, 28, 335-342, 2000
- Jagannath, C., Emanuele, R.M., Hunter, R.L. Jr., Activity of poloxamer CRL1072 against drug sensitive and drug resistant strains of Mycobacterium tuberculosis in macrophages and mice, International Journal of Antimicrobial Agents, 15, 55-63, 2000
- Jagannath, C., et al., CRL-1072 enhances the antimycobacterial activity of human macrophages through IL-8, Journal of Interferon and Cytokine Research, 19, 67-76, 1999
- Jagannath, C, Wells, A, Mshilvdadze, M, Olsen, M, Emanule RM, Hunter RL and Dasgupta, A., Significantly improved oral uptake of amikacin in FVB mice in the presence of copolymer CRL-1605, Lifesciences, 64, 1773-1738, 1999
- Jagannath, C., Actor, J.K., R.L.Hunter, Induction of nitric oxide in human monocytes and monocyte cell lines by Mycobacterium tuberculosis, Nitric Oxide: Biology and Chemistry, 2, 174-186, 1998
- Newman M J, Actor J K, Balusubramanian M, Jagannath C, Use of nonionic block copolymers in vaccines and therapeutics., Critical Reviews In Therapeutic Drug Carrier Systems, 15(2), 89-142, 1998
- Jagannath C, Allaudeen H S, Hunter R L, Activities of poloxamer CRL8131 against Mycobacterium tuberculosis in vitro and in vivo, Antimicrobial Agents and Chemotherapy, 39(6), 1349-54, June 1995
- Jagannath C, Reddy MV, Kailasam S, O'Sullivan JF, Gangadharam PR, Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and in vivo studies, American Journal of Respiratory and Critical Care Medicine, 151(4), 1083-6, April 1995
- Jagannath C, Reddy V M, Gangadharam P R, Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide, Journal of Antimicrobial Chemotherapy, 35(3), 381-90, March 1995
- Hunter R L, Jagannath C, Tinkley A, Behling C A, Nolte F, Enhancement of antibiotic susceptibility and suppression of Mycobacterium avium complex growth by poloxamer 331, Antimicrobial Agents and Chemotherapy, 39(2), 435-9, February 1995
- Hunter.R.L, Olsen, M, C. Jagannath, & J.K.Actor. (2006) Trehalose 6,6' dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice, Amer.J.Pathology, 168, 1249-61
- Hunter, R. L., M. R. Olsen, C. Jagannath, and J. K. Actor. (2006) Multiple roles of cord factor in the pathogenesis of primary, secondary, and cavitary tuberculosis, including a revised description of the pathology of secondary disease, Ann Clin Lab Sci, 36, 371-386
- Marek Fol, Ashwini Chauhan, Erin Maloney, Meredith Moomey, Murty V. Madiraju , C. Jagannath and Malini Rajagopalan. (2006) Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator, Molecular Microbiology, 60, 643-57
- Christopher R.Singh, Lisa Y. Armitige, Amanda K. Smith, S.Dhandayuthapani, Akil Bidani. Robert L Hunter. Jr. & C. Jagannath (2006) Processing and presentation of a mycobacterial antigen 85B epitope by murine macrophages is dependent upon the phagosomal acquisition of vacuolar proton ATPase and in situ activation of Cathepsin D, J.Immunology, 177, 3250-9
- Sundarsingh Daniel*, Guixiang Dai*, Devin R. Lindsey, Christopher R.Singh, Amanda K. Smith, S..Dhandayuthapani, Robert L Hunter. Jr. & C. Jagannath. (2006) Reduced bactericidal function of Complement C5 deficient murine macrophages is in part due to a defective assembly of phagocyte oxidase, J.Immunology, 177, 4688-98
- Connelly.M.A*, Moulton.R.A*, Smith.A.K, Lindsey.D.R, Zwirner,J & C. Jagannath. (2007) Mycobacteria primed macrophages and dendritic cells induce an up- regulation of Complement C5a anaphylatoxin receptor (CD88) in CD3+ murine T cells, J.Leucocyte Biology, 81, 212-20
- Hunter, R. L., C. Jagannath, and J. K. Actor. (2007) Pathology of Postprimary Tuberculosis in Humans and Mice: Contradiction of long-held beliefs, Tuberculosis (Edin), 87, 267-78
- Rachel Moulton, Mary Anne Connelly,Amanda K. Smith, Devin R.Lindsey, Rick A.Wetsel, David L.Haviland, Robert L Hunter. Jr. & C. Jagannath., Complement C5a anaphylatoxin is an innate determinant of dendritic cell mediated Th1 immunity during Mycobacterium bovis BCG infection in mice.
- Jacek Szeliga, Daniel D. Sundarsingh, Ching-Hui Yang, Zvjezdana Sever-Chroneos, Chinnaswamy Jagannath, Zissis Chroneos., Granulocyte macrophage colony stimulating factor-mediated innate responses in tuberculosis. Tuberculosis (Edin) TUBE-D-07-00020. 2007 (in press).
- Xu,Y, C.Jagannath & Tony Eissa., Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity; 2007 (in press).
Profile Details
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COS Expertise ID #412923
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