B.A., Biology, 1976. University of Virginia at Charlottesville
Ph.D., Microbiology and Immunology, 1988. Emory University, Atlanta, GA
Post-doctoral Fellow, 1988-1992. Uniformed Services University of the Health Sciences, Bethesda, MD
My laboratory studies the pathogenesis of diseases caused by Shiga toxins, a family of genetically and functionally related protein toxins expressed by the enteric pathogens Shigella dysenteriae type 1 and select serotypes of Escherichia coli. Shiga toxin-producing E. coli have been in the news lately as ingestion of ground beef, spinach or well water contaminated with the toxin-producing organisms has resulted in widespread outbreaks of bloody diarrhea. Unfortunately, patients with these diarrheal diseases are at increased risk for developing life-threatening extra-intestinal complications including acute renal failure and neurological abnormalities. There are several research projects ongoing in the laboratory: (i) characterization of intracellular signaling pathways activated by Shiga toxins in macrophages leading to the increased expression of proinflammatory cytokines; (ii ) characterization of toxin- induced signaling pathways leading to apoptosis; (iii) examination of the roles of proinflammatory cytokines and apoptosis in pathogenesis using a murine model of Shiga toxin-induced renal damage; (iv) characterization of the global transcriptional response of human macrophages to Shiga toxins using microarray analysis; and (v) examination of the capacity of Shiga toxins to elicit the ER stress response.
Ramegowda, B., and V.L. Tesh. Differentiation-associated toxin receptor modulation, cytokine production and sensitivity to Shiga-like toxins in human monocytes and monocytic cell lines. Infection and Immunity 64:1173-1180 (1996).
Sakiri, R., B. Ramegowda, and V.L. Tesh. Shiga toxin type 1 activates tumor necrosis factor-α gene transcription and nuclear translocation of the transcriptional activators nuclear factor-κB and activator protein-1. Blood. 92:558-566 (1998).
Taylor Jr, F.B., V.L. Tesh, L. DeBault, A. Li, A.C.K. Chang, S.D. Kosanke, T. J. Pysher, R.L. Siegler. Characterization of the baboon responses to purified Shiga-like toxin: descriptive study of a new primate model of toxic response to Stx-1. American Journal of Pathology. 154:1285-1299 (1999).
Ramegowda, B., J.E. Samuel, and V.L. Tesh. Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents. Journal of Infectious Diseases. 180:1205-1213 (1999).
Foster, G.H., C.S. Armstrong, R. Sakiri, and V.L. Tesh. Shiga toxin induced tumor necrosis factor-α expression: requirement for toxin enzymatic activity and monocyte PKC and protein tyrosine kinases. Infection and Immunity. 68:5183-5189 (2000).
Foster, G.H., and V.L. Tesh. Shiga toxin 1-induced activation of c-Jun NH2-terminal kinase and p38 in the human monocytic cell line THP-1: possible involvement in the production of TNF-α. Journal of Leukocyte Biology. 71:107-114 (2002).
Cherla, R.P., S.-Y. Lee, and V.L. Tesh. Shiga toxins and apoptosis. FEMS Microbiology Letters. 228:159-166 (2003).
Harrison, L.M., W. C. E. van Haaften, and V.L. Tesh. Regulation of pro-inflammatory cytokine expression by Shiga toxin 1 and/or lipopolysaccharides in the human monocytic cell line THP-1. Infection and Immunity. 72:2628-2627 (2004).
Harrison, L.M., C. van den Hoogen, W.C.E. van Haaften, and V.L. Tesh. Chemokine expression in the monocytic cell line THP-1 in response to purified Shiga toxin 1 and/or lipopoly-saccharides. Infection and Immunity. 73:403-412 (2005).
Harrison, L.M., R.P. Cherla, C. van den Hoogen, W.C. E. van Haaften, S.-Y. Lee, and V.L. Tesh. Comparative evaluation of apoptosis induced by Shiga toxin 1 and/or lipopolysaccharides in human monocytic cells and macrophage-like cells. Microbial Pathogenesis. 38:11-24 (2005).
Lee, S.-Y., R.P. Cherla, I. Caliskan, and V.L. Tesh. Shiga toxin 1 induces apoptosis in the human myelogenous leukemia cell line THP-1 by a caspase 8-dependent, TNF receptor-independent mechanism. Infection and Immunity. 73:5115-5126 (2005).
Cherla, R.P., S.-Y. Lee, P.L. Mees, V.L. Tesh. Shiga toxin 1 induced cytokine production is mediated by MAP kinase pathways and translation initiation factor eIF4E in the macrophage-like THP-1 cell line. Journal of Leukocyte Biology. 79:397-407 (2006).Lee, S.-Y., R.P. Cherla, and V.L. Tesh. Simultaneous induction of apoptotic and cell survival signaling pathways in macrophage-like THP-1 cells by Shiga toxin 1. Infection and Immunity. 75:1291-1302 (2007