James C. Alwine, Ph.D.

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Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations

Contact information
314 Biomedical Research Building
421 Curie Blvd.
School of Medicine
University of Pennsylvania
Philadelphia, PA 19104-6160
Office: (215) 898-3256
Fax: (215) 573-3888
Education:
B.S. (Chemistry)
Elizabethtown College, Elizabethtown, Pennsylvania, 1969.
Ph.D. (Biological Chemistry)
The Milton S. Hershey Medical Center of the Pennsylvania State University. Research in molecular biology with Dr. Charles W. Hill., 1974.
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Description of Research Expertise

Research Interests

Dr. Alwine’s research career has centered on DNA viruses and how they manipulate cellular systems to their advantage during infection and transformation. He has made numerous significant contributions beginning with his postdoctoral work where he showed that Simian virus 40 (SV40) large T antigen regulated the transcription of its own gene, the first demonstration of transcriptional autoregulation in a eukaryotic system. During this period he also developed the RNA transfer technique which he named the Northern Transfer. During his 33 years at the University of Pennsylvania he has continued to study SV40 and expanded to human cytomegalovirus (HCMV). He studied transcriptional activation by both viruses showing that both SV40 large T antigen and the HCMV major immediate early proteins interact with the basal transcription complex and facilitate its formation on promoters. He extended his studies to the analysis of viral polyadenylation signals and how they functioned. His work defined control elements both upstream and downstream of the AAUAAA polyadenylation signal which affect polyadenylation efficiency in both viral and cellular mRNAs.

Over the past 14 years he has focused his research on understanding the means by which viruses alter cellular signaling, especially stress signaling, and modify cellular metabolism. He has been among the first to study: how HCMV alters the PI3K-Akt-mTOR pathway to resist inhibition by cellular stress; how HCMV alters the signaling pathways of the unfolded protein response for the advantage of the viral infection; and how HCMV alters cellular metabolism. The cumulative findings suggest that the pathogenic effects of these alterations could implicate HCMV, and related DNA viruses, as subtle co-factors in many maladies. For example, many of the pathways his lab has found to be altered by HCMV are also altered during oncogenesis. Additionally, the HCMV-mediated alterations of metabolism are very similar to what occurs in many tumor cells. While not suggesting that HCMV is a frank transforming agent, the data suggest that the effects of the viral infection on cellular pathways serve as one step among several that may promote transformation or increase malignancy.

Selected Publications

Chambers JW, Maguire TG, Alwine JC: Glutamine metabolism is essential for human cytomegalovirus infection. Journal of Virology 84(4): 1867-73, Feb 2010.

Buchkovich NJ, Maguire TG, Alwine JC: Role of the endoplasmic reticulum chaperone BiP, SUN domain proteins, and dynein in altering nuclear morphology during human cytomegalovirus infection. Journal of Virology 84(14): 7005-17, Jul 2010.

Yu Y, Maguire TG, Alwine JC: Human cytomegalovirus activates glucose transporter 4 expression to increase glucose uptake during infection. Journal of Virology 85(4): 1573-80, Feb 2011.

Clippinger AJ, Maguire TG, Alwine JC: Human cytomegalovirus infection maintains mTOR activity and its perinuclear localization during amino acid deprivation. Journal of Virology 85(18): 9369-76, Sep 2011.

Yu Y, Maguire TG, Alwine JC: Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. Journal of Virology 86(6): 2942-9, Mar 2012.

Clippinger AJ, Alwine JC: Dynein mediates the localization and activation of mTOR in normal and human cytomegalovirus-infected cells. Genes & Development 26(18): 2015-26, Sep 2012.

Yu Y, Pierciey FJ Jr, Maguire TG, Alwine JC: PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection. PLoS Pathogens 9(4): e1003266, Apr 2013.

Yu Y, Clippinger AJ, Alwine JC: Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends in Microbiology 19(7): 360-7, July 2011.

Alwine JC: DNA Viruses and Cancer: Taking a Broader Look. Cancer Associated Viruses Series “Current Cancer Research" E. Robertson (eds.). Springer, New York, N.Y. Page: 119-132, 2012.

Yu Y, Clippinger AJ, Alwine JC: Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends in Microbiology 19(7): 360-7, Jul 2011.

Alwine JC: The Human Cytomegalovirus Assembly Compartment: A Masterpiece of Viral Manipulation of Cellular Processes That Facilitates Assembly and Egress. PLoS Pathogens 8(9): e1002878, Sep 2012.

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Last updated: 11/01/2013
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