UCSD | Department of Chemistry&Biochemistry -- Faculty & Research

Partho Ghosh
Mechanisms of bacterial and protozoan pathogenesis, and host response against infectious microbes.

Contact Information

Office: NSB 3105

Phone: (858) 822-1139

Fax: (858) 822-2871

Email: pghosh@ucsd.edu

Group Website: http://pghosh.ucsd.edu/

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Education and Appointments
1997	Postdoc, Harvard University
1992	Ph. D., University of California, San Francisco
1985	B.S., Yale University

Awards and Academic Honors
2000	Burroughs-Wellcome New Initiatives in Malaria
1999	W. M. Keck Distinguished Young Scholar in Medicine
1999	Hellman Faculty Fellow

Research Interests
Research in my laboratory is dedicated to understanding the basis of infectious disease at molecular and cellular levels. We focus on mechanisms by which virulence factors produced by pathogenic microbes interact with host cell targets and thereby modulate host cell behavior during infection. We study these interactions in structural detail (i.e., at the level of atomic resolution through X-ray crystallography) in order to carry out precise biochemical, genetic, and cell biological experiments aimed at elucidating the mechanism of action of bacterial virulence factors in their cellular context. Our studies focus on the initial interaction between a pathogen and a host cell, and how this interaction resolves as induction of intracellular entry or inhibition of phagocytic uptake. Induction of intracellular entry is exemplified by studies on Listeria monocytogenes. We are delving into how the L. monocytogenes protein InlB activates the host cell receptor tyrosine kinase Met (hepatocyte growth factor receptor, HGFR) to effect host cell invasion. Met is a proto-oncogene and therefore we hope to understand general rules of regulation of such crucial mediators of host cell growth through studies of InlB. Inhibition of phagocytic uptake is being pursued through studies on the mechanism of protein translocation into host cells by the Yersinia pseudotuberculosis type III secretion system as well as on antiopsonic surface proteins of Group A Streptococcus. In a broader sense, macromolecular recognition is at the heart of all these processes, and we are pursuing diversity-generating retroelements and the massively sequence variable protein repertoires that they produce in order to understand the general rules underlying specificity in molecular recognition.
Primary Research Area:	Interdisciplinary Specialties:
Biochemistry	Biophysics Macromolecular Structure Cellular Biochemistry
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Selected Publications

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.

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

Phillips, R. M., Six, D., Dennis, E., & Ghosh, P. (2003) In vivo phospholipase activity of the Pseudomonas aeruginosa cytotoxin ExoU and protection of mammalian cells with phospholipase A2 inhibitors. Journal of Biological Chemistry 278:41326-41332.

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 SA, Miller JL, Lawton JA, Kerkow DE, Hodes A, Marti-Renom MA, Doulatov S, Narayanan E, Sali A, Miller JF, Ghosh P, "The C-type lectin fold as an evolutionary solution for massive sequence variation." Nat Struct Mol Biol 10(886-92): , 2005. [Go to PubMed]

Miller JL, Le Coq J, Hodes A, Barbalat R, Miller JF, Ghosh P, "Selective ligand recognition by a diversity-generating retroelement variable protein." PLoS Biol 6(e131): , 2008. [Go to PubMed]

McNamara C, Zinkernagel AS, Macheboeuf P, Cunningham MW, Nizet V, Ghosh P, "Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence." Science 5868(1405-8): , 2008. [Go to PubMed]