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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Microbiology
Molecular Microbiology
Office: (214) 648-5940
Fax: (214) 648-5905
Building: NA, Room 6.300
Email: michael.gale@utsouthwestern.edu
Our laboratory research is
directed toward understanding the molecular virology of hepatitis C virus (HCV)
and cellular pathogenesis due to HCV infection. Current studies in our
laboratory are focused on 1) Defining the interactions between HCV and the
innate cellular antiviral pathways that are triggered immediately after
infection, 2) Characterizing viral sequences that confer regulation of the host
antiviral response and contribute to replication efficiency in vitro, and 3)
Identifying cellular and viral targets which will direct the development of new
anti-HCV therapies. HCV has emerged as a major public health problem, and
approximately 200 million people worldwide are persistently infected with the
virus. Our results indicate that replication efficiency and viral
persistence are linked to the ability of HCV to regulate antiviral response
pathways within the infected cell, including those involving interferon
regulatory factors (IRFs) and the cellular PKR protein kinase. Through
multiple strategies, HCV disrupts IRF activation and inhibits PKR function,
supporting persistent infection and allowing the virus to largely escape the
cellular antiviral response.
In addition to its role as an antiviral effector, PKR plays a role within a
larger regulatory pathway to control cellular mRNA translation in response to
specific regulatory signals. A second major aim in our lab is to
understand how processes that impact PKR function and mRNA translation may
contribute to regulation of cell growth and proliferation in normal, dividing
cells. We are characterizing the components of the PKR regulatory pathway
in human cells, and have identified a novel upstream regulator of PKR, termed
P52 rIPK . We have found that P52 rIPK plays a pivotal
role in integrating stress-induced and growth-regulatory signals into the PKR
regulatory pathway, thereby providing a signaling network that directs the
control of mRNA translation. Within this project our current studies are
focused on 1) characterizing the P52 rIPK -dependent PKR signaling
pathway, and 2) utilizing genome expression array technology to identify
substrate mRNAs that are translationally regulated in response to P52 rIPK -dependent
signaling.
Selected Publications:
Milling, W.M., Pflugheber, J.,
and M. Gale Jr. (2001) Control of double-stranded RNA signaling and IRF-1
activation by the hepatitis C virus NS5A protein. Submitted.
Sumpter, R., Pflugheber, J., and
M. Gale Jr. (2001) The mechanism of interferon antiviral action on
hepatitis C virus RNA replication. Submitted.
Gale, M. Jr., Blakely, C.M.,
Thomas, S., Darveau, A., Romano, P. R., Disteche, C., and Katze, M.G (2001)
The charged domain of P52 rIPK confers regulation of P58 IPK
and defines a novel stress-signaling pathway that modulates control of PKR
activity and mRNA translation. Submitted.
Gale, M. Jr. , S.L. Tan, and M.G. Katze (2000)
Translational control of viral gene expression in eukaryotes. Microbiol.
and Mol. Biol. Revs.
Gale, M., Jr., B. Kwieciszewski, M. Dossett, H. Nakao,
and M.G. Katze (1999) Anti-apoptotic and oncogenic potentials of hepatitis C
virus are linked to interferon resistance by viral repression of the PKR protein
kinase. J.Virol. 73:6506-6516.
Gale, M., Jr., C.M. Blakely, D.A. Hopkins, M.W.
Melville, M. Wambach, P.R. Romano, and M.G. Katze (1998) Regulation of
interferon-induced protein kinase PKR: modulation of P58 IPK inhibitory
function by a novel protein, P52 rIPK . Mol.Cell.Biol.
18:859-871.
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Last updated: 18 May 2001
Extraction Method: Expand using Medical Synonyms-
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