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Pancholi, Vijay
Dr. Pancholi’s laboratory is primarily interested in understanding the cellular and molecular basis of the host–pathogen interaction between gram-positive bacterial pathogens (group A Streptococcus or Streptococcus pyogenes or GAS in particular) and their specific hosts. GAS causes a variety of diseases of the human pharynx and the skin. The severity of these diseases ranges from mild pharyngitis and impetigo to severe, invasive, rapidly progressing and often fatal necrotizing fasciitis (Flash eating bacterial symptoms) and toxic shock syndromes. GAS pharyngitis and skin infections are often associated with post streptococcal autoimmune diseases such as acute rheumatic fever (ARF)/heart diseases (RH) and post streptococcal acute glomerulonephritis (PSAGN). RH/ARF is one of the major contributors of the cardiovascular morbidity in developing countries. Bacterial surface proteins play a key role in the disease process. Hence, Dr. Pancholi’s immediate goal is to understand the role of streptococcal surface proteins in the initial and late stages of streptococcal infection by deciphering the biochemical language used for the effective communication between the host and pathogen. Dr. Pancholi has identified a novel class of proteins on the surface of group A streptococci that has structural and functional similarities with eukaryotic glycolytic enzymes (glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, phosphoglycerate kinase, phosphoglycerate mutase, and enolase ) and are responsible for the production of ATP. These proteins lack classical structural machineries required for the surface transport and hence they are called anchorless surface proteins. The selective presence of ATP-producing sequential glycolytic enzymes on the surface of group A streptococci and many other gram-positive cocci, fungus and parasites, make this finding novel not only for gram positive bacteria but also for the bacterial/microbial surface protein field in general. Using several molecular and biochemical approaches, his research team is now investigating multifunctional nature of these glycolytic enzymes and the nature of a putative transport system responsible for the surface expression of this unique class of streptococcal surface proteins. Streptococcal-host cell interaction like many other pathogen-host interactions is very dynamic and involves effective cell-cell communications which may have direct relevance to their ability to adhere, colonize, invade and further proliferate in the host. Since the most common site of group A streptococcal infection is the tonsil/pharynx, Dr. Pancholi and his research team have chosen to focus on the streptococcal infection of tonsillar/pharyngeal cells by defining the intracellular signaling events regulated as a result of their interaction with group A streptococci using various biochemical and genetic approaches. His research team has shown that streptococcal surface dehydrogenase (SDH) is a multifunctional protein. It regulates host cell phosphorylation events and causes apoptosis of pharyngeal cells. To understand the role of SDH and other streptococcal surface glycolytic enzymes during various stages of streptococcal infection, Dr. Pancholi’s research team is interested in identifying and characterizing these protein-specific host cell receptors, deciphering host cell signaling events, and studying gene expression profiles in the host cell as well as in Streptococcus pyogenes using microgene array technology. More recently, Dr Pancholi’s lab has identified a novel eukaryotic-type signaling system in GAS. This system seems to play an important role in the regulation of bacterial virulence, metabolism, growth, cell division, and bacterial ability to interact with host cells. Besides studying the biochemical mechanism of this regulation, Dr. Pancholi’s laboratory is also interested in understanding how GAS utilizes its eukaryotic-type bacterial signaling system to exploit host cell machinery for their own advantage for survival and proliferation in the targeted host. The goal of Dr. Pancholi’s lab is to utilize these approaches to make possible the development of rational chemotherapeutic and immunotherapeutic interventions to effectively counteract GAS- and multidrug resistant-gram-positive pathogens-mediated acute and late tissue destruction. Selected Publications Pancholi, V., Fontan, P. and Jin, H.(2003) Plasminogen-mediated group A streptococcal adherence to and pericellular invasion of human pharyngeal cells. Microb. Pathog. 35: 293-303. Pancholi, V., and Chhatwal,G.S.(2003). Housekeeping enzymes as virulence factors. Int. J.Med. Microbiol. 293:391-401. Derbise, A., SONG, Y. P. PARIKH, S., Fischetti, V.A. and Pancholi, V.(2004) Role of the C-terminal lysine residues in the SEN-mediated plasminogen binding property of group A streptococci. Infect. Immun. 72:94-105. Jin, H., Song, Y. P., Boel, G., Kochar, J. and Pancholi, V. (2005) Group a streptococcal surface GAPDH, SDH, recognizes uPAR/CD87 as its receptor on the human pharyngeal cell and mediates bacterial adherence to host cells. J. Mol. Biol. 350:27-41. Boel, G., Jin, H. and Pancholi, V. (2005) Inhibition of cell surface export of group A streptococcal anchorless surface dehydrogenase (SDH) affects bacterial adherence and antiphagocytic properties. Infect. Immun. 73: 6237-634. Pancholi, V. (2006): Streptococci-mediated host cell signaling In: Gram-Positive Pathogens. V.A. Fischetti, R. Novick, J.Ferreti, D.Portnoy, J.Rood (Eds) 2nd edition. ASM publications, Washington D.C. USA JIN, H. AND PANCHOLI, V. (2006) Identification and biochemical characterization of a eukaryotic-type serine/threonine kinase and its cognate phosphatase in Streptococcus pyogenes: Their biological functions and substrate identification. J. Mol. Biol. 357:1351-1372. SUNDBLAD, V., BUSSMANN, L., CHIAUZZI, V.A.., PANCHOLI, V., CHARREAU, E.H. (2006) a-enolase: A novel autoantigen in patients with premature ovarian failure. Clin. Endocrinol. 65:745-751. PANCHOLI, V. (2006): Streptococcus-mediated host cell signaling In: Gram-Positive Pathogens. V.A. Fischetti, R. Novick, J.Ferreti, D.Portnoy, J.Rood (Eds) 2nd edition, p100-112. ASM Publications, Washington D.C. USA. Pancholi Laboratory Personnel
Hong Jin Postdoctoral Researcher Contact e-mail: vijay.pancholi@osumc.edu |
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Vijay Pancholi, Ph.D. is an Associate Professor appointed in the Department of Pathology. Before joining the OSU faculty in 2005, he was a faculty member at the Rockefeller University from 1992-1999 and then at the Public Health Research Institute, Newark, NJ.