Partho Ghosh
 Associate Professor of Biology & Biochemistry, UCSD

e-mail: pghosh@ucsd.edu
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Our research is focused on understanding mechanisms used by microbial pathogens to cause infectious disease. In particular, we are studying how bacterial pathogens manipulate host cell behavior to effect infection. Bacterial pathogens are a re-emerging threat to human health and welfare due to the increasing incidence of multidrug resistant strains, and a number of bacterial pathogens also pose threats as bioterror agents. The process of manipulating host cell behavior almost always occurs through interaction between bacterial proteins, termed virulence factors, and host cell proteins. These interactions then trigger a set of changes in the host cell that are beneficial to the infection process. We seek to understand the role of host-pathogen interactions in infection at the molecular and cellular levels through a variety of techniques, including structural biology, biochemistry, genetics, and cell biology.

Of primary interest are mechanisms used by intracellular pathogens to gain entry into host cells. A large variety of pathogens are known to adopt an intracellular lifestyle, and we have been dissecting how such pathogens gain entry into non-phagocytic host cells. In this area, we have focused on InlB, a protein that effects invasion of the bacterial, food-borne pathogen Listeria monocytogenes into a wide variety of mammalian cells. We are also studying the type III secretion system, a mechanism used by a wide variety of Gram-negative bacterial pathogens to inject proteins directly into host cells. We are trying to understand the secretion process in the bacterial pathogen Yersinia pseudotuberculosis, as well as the function of bacterial proteins that are translocated by other bacterial pathogens, such as Pseudomonas aeruginosa.

    Marino, M., Braun, L., Cossart, P. & Ghosh, P. (1999). Structure of the InlB leucine rich repeats, a domain that triggers host cell invasion by the bacterial pathogen L. monocytogenes. Molecular Cell 4:1063-1072.

    Buetow, L., Flatau, G., Chiu, K., Boquet, P. & Ghosh, P. (2001). The structure of the Rho-activating domain of E. coli cytotoxic necrotizing factor type 1. Nature Structural Biology 8:584-588.

    Birtalan, S. & Ghosh, P. (2001). Structure of the Yersinia type III secretory system chaperone SycE. Nature Structural Biology 8:974-978.

    Birtalan, S, C., Phillips, R. M. & Ghosh, P. (2002). Three-dimensional signals in chaperone-effector complexes of bacterial pathogens. Molecular Cell 9:971-980.

    Marino, M., Banerjee, M., Jonquières, R., Cossart, P. & Ghosh, P. (2002). GW domains of the L. monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands. EMBO J. 21:5623-5634.

    Banerjee, M., Copp, J., Vuga, D., Marino, M., Chapman, T., van der Geer, P & Ghosh, P. (2004). GW domains of the L. monocytogenes invasion protein InlB are required for potentiation of Met activation. Molecular Microbiology 52(1):257-271.

    McMahon, S.A., Miller, J.L., Lawton, J.A., Kerkow, D.E., Hodes, A., Marti-Renom, M., Doulatov, S., Narayan, E., Sali, A., Miller, J.F. & Ghosh, P. (2005). The C-type lectin fold as an evolutionary solution for massive sequence variation. Nature Structural and Molecular Biology. 12(10):886-892.
Partho Ghosh received his Ph.D. from the University of California, San Francisco. He carried out postdoctoral research at Harvard University as an Irvington Institute for Medical Research Fellow. He was also the recipient of a W.M. Keck Foundation Distinguished Young Scholars in Medicine award.