Vernon L. Tesh, Ph.D.
Vice President for Academic Affairs
Department of Microbial Pathogenesis and Immunology
Clinical Bldg. 1, Suite 3100Bryan, TX 77807
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).