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Susheela Tridandapani, PhD
Professor
Research Director, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine
201 Davis Heart and Lung Research Institute
473 West 12th Avenue
Columbus, OH 43210
Phone: (614) 247-6768
click here to read CV
Research Interests
Intracellular signaling mechanisms that regulate macrophage innate immune responses with an emphasis on response to IgG immune-complexes (IC) and bacterial ligands.
Project 1: Macrophage Fc Receptor function.
One major goal of the lab is to understand the regulation of expression and function of IgG receptors (Fc?R) in monocytes and macrophages. Fc?R bind to and clear IgG-antigen by phagocytosis. This property of macrophages is central to the efficacy of monoclonal antibody therapy for cancer. The phagocytic process is often accompanied by the generation of inflammatory cytokines and reactive oxygen and nitrogen radicals, which can result in collateral tissue damage unless tightly regulated.
Recent work from our laboratory and others established that the phagocytic process is subject to multiple regulatory mechanisms. One level of regulation occurs by the modulation of the ratio of activating to inhibiting Fc?R on monocytes and macrophages. A second level of regulation is mediated by intracellular phosphatases (inositol phosphatases, protein tyrosine phosphatases). Ongoing research in the laboratory is aimed at understanding the molecular details of these regulatory mechanisms.
Project 2: Mechanisms of macrophage response to Francisella infection
Francisella tularensis primarily infects monocytes and macrophages, subverts host responses and causes the disease Tularemia. Molecular details of host cell responses to infection and the subversive strategies employed by the pathogen are poorly characterized. The goal of this project is to first unravel the biochemical pathways activated by Francisella infection of macrophages, and the regulatory mechanisms that are in place to maintain homeostasis. Second, we aim to define the mechanisms of host response subversion by virulent Francisella.
We use multiple approaches, including microarray analyses, microRNA analyses, biochemical, signal transduction and molecular biology approaches to gain an understanding of host responses. We anticipate that once these molecular mechanisms are defined one can devise therapeutic approaches to boost host resistance to infection.
Recent Publications
Ganesan, L.P., Joshi, T., Fang, H., Kutala, V.K., Roda, J., Trotta, R., Lehman, A., Kuppusamy, P., Byrd, J.C., Carson, W.E., Caligiuri, M.A.and S. Tridandapani. (2006) Fc?R-induced production of superoxide and inflammatory cytokines is differentially regulated by SHIP through its influence on PI3K and/or Ras/Erk pathways. Blood. 108(2):718-25
Parsa, K.V.L., Ganesan, L.P., Rajaram, M.V.S., Gavrilin, M. A., Balagopal, A., Mohapatra, N., Wewers, M.D., Gunn, J.S., and S. Tridandapani (2006). Macrophage pro-inflammatory response to Francisella novicida infection is regulated by the SH2 domain-containing inositol phosphatase SHIP. PLoS Pathogens 2(7):e71
Rajaram, M.V.S., Ganesan, L.P., Parsa, K.V.L., Butchar, J.P., Gunn, J.S., and S. Tridandapani (2006) Akt/PKB modulates macrophage inflammatory response to Fransicella infection and confers a survival advantage in mice. J. Immunol. 177(9):6317-24
Butchar, J.P., Rajaram, M.V.S., Ganesan, L.P., Parsa, K.V.L., Clay, C.D., Schlesinger, L.S. and S. Tridandapani. (2007) Francisella tularensis induces interleukin-23 production in human monocytes. J. Immunol.178(7):4445-54.
Parsa, K.V.L, Butchar, J. P., Rajaram, M.V.S and S. Tridandapani. (2008) The tyrosine kinase Syk promotes the uptake of Francisella through the activation of Erk. Mol. Immunol.. 45(10):3012-21
Butchar, J.P., Parsa, K.V.L., Marsh, C.B. and S. Tridandapani. (2008) IFNgamma enhances IL-23 production during Francisella infection of human monocytes. FEBS Letters. 582(7):1044-8.
Parsa, K.V.L, Butchar, J. P., Rajaram, M.V.S., Gunn, J. S., Schlesinger, L. S. and S. Tridandapani. (2008) Francisella gains a survival advantage within mononuclear phagocytes by suppressing host IFN? response. Mol. Immunol.45(12):3428-37
Butchar JP, Cremer TJ, Clay CD, Gavrilin MA, Wewers MD, Marsh CB, Schlesinger LS and S Tridandapani. (2008) Microarray analysis of human monocytes infected with Francisella tularensis identifies new targets of host response subversion. PLoS ONE 3(8):e2924.
Cremer, J.J., Amer, A. O., Tridandapani, S. and J. P. Butchar. (2008). Francisella tularensis regulates autophagy-related pathways. Autophagy 5(1):125-8.
Joshi, T., Ganesan, L., Cheney, C., Ostrowski, M., Muthusamy, N., Byrd, J. C. and S. Tridandapani. (2009) The PtdIns 3-kinase/Akt pathway regulates macrophage-mediated ADCC against B cell lymphoma. PLoS ONE. 4(1):e4208
Rajaram, M.V.S., Butchar, J. P., Parsa, K.V.L., Amer, A., Schlesinger, L.S. and S. Tridandapani. (2009) Akt and SHIP modulate Francisella escape from the phagosome and the induction of the Fas-mediated death pathway. PLoS ONE. In Press
Lab Members:
Jonathan P. Butchar, PhD (Research Scientist)
Steven Justiniano, PhD (Postdoc)
Thomas Cremer (Grad. Student, MCDB)
Payal Mehta (Grad. Student, OSBP)
Yufen Wang (Research Assistant)
Oliver Knoell
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