Karen A. Skorupski, Ph.D.
Associate Professor of Microbiology and Immunology
Microbiology and Immunology
Rutgers - The State University, Ph.D ., 1988
University of New Haven, B.S., 1982
University of New Haven, A.S., 1980
After postdoctoral work at the DuPont Merck Pharmaceutical Company and in the Department of Microbiology at Dartmouth Medical School, Dr. Skorupski joined the faculty of the Department of Microbiology at Dartmouth Medical School in 1997.
Dartmouth Medical School
Vail Building - HB 7550
Hanover NH 03755
Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. We are interested in the regulation of virulence gene expression during V. cholerae infection. Toxigenic strains of V. cholerae possess two distinct phage derived pathogenicity islands, VPI which encodes the toxin-coregulated pilus (TCP), an essential colonization factor, and CTX which encodes cholera toxin (CT). We have recently identified two new transcriptional regulators, AphA and AphB, which function synergistically to activate the expression of TCP and CT by activating the expression of a membrane bound transcriptional activator, TcpP, which is encoded on the VPI. AphA appears to be a novel type of transcriptional activator with no known homologs and AphB is a member of the LysR family. The activation of TcpP by AphA and AphB occurs only under certain environmental conditions and appears to be the initial regulatory step in the virulence transcriptional cascade. Mutants defective for either one of these genes are attenuated in the infant mouse cholera model. Interestingly, AphA and AphB are not themselves encoded on the VPI or CTX elements but are located in regions of the V. cholerae chromosome not previously associated with pathogenesis. Thus, these proteins are likely to play a role in normal cellular physiology and function to couple physiological responses with virulence gene expression. We are utilizing a combination of genetic and biochemical approaches to elucidate the mechanism of AphA and AphB mediated transcriptional activation of tcpP and to understand how these two proteins couple environmental conditions to the expression of virulence genes. Since LysR regulators are known to require small molecule coinducers present under certain conditions to activate gene expression, it is hoped that these studies will lead to the identification of new targets for antimicrobial design.
Almagro-Moreno S, Kim TK, Skorupski K, Taylor RK
Shi W, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
Cerda-Maira FA, Kovacikova G, Jude BA, Skorupski K, Taylor RK
Taylor JL, De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
Stonehouse EA, Hulbert RR, Nye MB, Skorupski K, Taylor RK
Kovacikova G, Lin W, Skorupski K
Martinez RM, Jude BA, Kirn TJ, Skorupski K, Taylor RK
Lowden MJ, Skorupski K, Pellegrini M, Chiorazzo MG, Taylor RK, Kull FJ
Jude BA, Martinez RM, Skorupski K, Taylor RK
Stonehouse E, Kovacikova G, Taylor RK, Skorupski K