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Karen A. Skorupski, Ph.D.

Title(s):
Associate Professor of Microbiology and Immunology

Department(s):
Microbiology and Immunology

Education:
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.

NIH Biosketch:
Skorupski_K_BIO_2009-02-16.pdf

Websites:
http://dms.dartmouth.edu/microbio/
http://dms.dartmouth.edu/immuno/

Contact Information:

Dartmouth Medical School
Vail Building - HB 7550
Hanover NH 03755

Phone: 603-650-1623
Fax: 603-650-1318
Email: Karen.A.Skorupski@Dartmouth.EDU


Professional Interests:

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.


Selected Publications:

 

Cerda-Maira FA, Kovacikova G, Jude BA, Skorupski K, Taylor RK
Characterization of BreR interaction with the bile response promoters breAB and breR in Vibrio cholerae.
J Bacteriol 2013 Jan; 195(2):307-17
PMID: 23144245

Taylor JL, De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
The crystal structure of AphB, a virulence gene activator from Vibrio cholerae, reveals residues that influence its response to oxygen and pH.
Mol Microbiol 2012 Feb; 83(3):457-70
PMID: 22053934

Stonehouse EA, Hulbert RR, Nye MB, Skorupski K, Taylor RK
H-NS binding and repression of the ctx promoter in Vibrio cholerae.
J Bacteriol 2011 Feb; 193(4):979-88
PMID: 21169492

Kovacikova G, Lin W, Skorupski K
The LysR-type virulence activator AphB regulates the expression of genes in Vibrio cholerae in response to low pH and anaerobiosis.
J Bacteriol 2010 Aug; 192(16):4181-91
PMID: 20562308

Martinez RM, Jude BA, Kirn TJ, Skorupski K, Taylor RK
Role of FlgT in anchoring the flagellum of Vibrio cholerae.
J Bacteriol 2010 Apr; 192(8):2085-92
PMID: 20154133

Lowden MJ, Skorupski K, Pellegrini M, Chiorazzo MG, Taylor RK, Kull FJ
Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes.
Proc Natl Acad Sci U S A 2010 Feb 16; 107(7):2860-5
PMID: 20133655

Jude BA, Martinez RM, Skorupski K, Taylor RK
Levels of the secreted Vibrio cholerae attachment factor GbpA are modulated by quorum-sensing-induced proteolysis.
J Bacteriol 2009 Nov; 191(22):6911-7
PMID: 19734310

Stonehouse E, Kovacikova G, Taylor RK, Skorupski K
Integration host factor positively regulates virulence gene expression in Vibrio cholerae.
J Bacteriol 2008 Jul; 190(13):4736-48
PMID: 18456804

De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR.
J Bacteriol 2007 Aug; 189(15):5683-91
PMID: 17526705

Lin W, Kovacikova G, Skorupski K
The quorum sensing regulator HapR downregulates the expression of the virulence gene transcription factor AphA in Vibrio cholerae by antagonizing Lrp- and VpsR-mediated activation.
Mol Microbiol 2007 May; 64(4):953-67
PMID: 17501920