The University of Toledo

James P. Trempe, Ph.D.

James P. Trempe, Ph.D. Vice President for Research Professor of Biochemistry and Cancer Biology james.trempe@utoledo.edu

RESEARCH INTERESTS:

The research in our laboratory is focused on the human parvovirus known as Adeno-associated Virus (AAV).  AAV is widespread in humans and primates but is considered nonpathogenic.  AAV is naturally defective in its life cycle in that it requires a coinfecting virus, such as human adenovirus, to replicate.  One of the very interesting characteristics about AAV is that it can suppress the oncogenic transformation of normal cells to a cancer cell phenotype.  Moreover, prior infection with AAV will limit the growth of tumors in animal models of tumorigenesis.  In order to learn how AAV suppresses tumor cell growth and proliferation, we are investigating how AAV interacts with the host cell and adenovirus, its helper virus.  Our studies have revealed that AAV induces a number of unique cellular responses in infected cells that may explain how the virus limits proliferation of tumor cells.

Another area of investigation for our laboratory is in AAV's use as a human gene therapy vector.  AAV’s harmless nature and inability to replicate on its own, makes it an excellent candidate viral vector for use in human gene therapy.  AAV vectors show great promise for human gene therapy and are currently involved in several clinical trials.  We are especially interested in developing AAV as a therapeutic agent against cancer. 

Our studies into the basic biology of AAV will enable us to make better use of AAV as a human gene therapy vector for the treatment of human disease.  By understanding how AAV interacts with the host cell, we will be able to harness its anti-oncogenic characteristics for the development of novel cancer therapeutic agents. 

EDUCATION:

B.S.   1976 Morehead State University, Morehead, KY (Dual Major, Biology and Chemistry)
Ph.D. 1984 Wright State University, Dayton, OH (Biomedical Sciences, Biochemistry)

ACADEMIC APPOINTMENTS:

2011-Present      Vice President for Research, The University of Toledo
2002-Present      Professor, Biochemistry and Cancer Biology, The University of Toledo Health Science Campus 
1998-1999          Acting Chairman, Biochemistry and Molecular Biology, Medical College of Ohio
1996-2002          Associate Professor with tenure, Biochemistry and Molecular Biology, Medical College of Ohio
1994-1996          Associate Professor, Biochemistry and Molecular Biology, Medical College of Ohio
1989-1994          Assistant Professor, Biochemistry and Molecular Biology, Medical College of Ohio
1985-1989          Senior Staff Fellow, Molecular and Cellular Biology, NIH (NIDDK)
1980-1984          Graduate Student, Biomedical Sciences, Wright State University

REPRESENTATIVE PUBLICATIONS:

Collaco, R. and Trempe, J.P. (2003) A method of helper virus-free production of adeno-associated virus vectors.  In:  Virus Vectors for Gene Therapy: Methods and Protocols.  Ed. C.A. Machida., Humana Press, Totowa, New Jersey, 76:237-254.

Smith, A.D., Collaco, R.F. and Trempe, J.P. (2003) Enhancement of recombinant adeno-associated virus type 2-mediated transgene expression in a lung epithelial cell line by inhibition of the epidermal growth factor receptor.  J. Virology 77:6394-6404.

Collaco, R., Kalman-Maltese, V., Smith, A.D., Dignam, J.D. and Trempe J.P. (2003) A biochemical characterization of the adeno-associated virus Rep40 helicase.  J. Biol. Chem. 278:34011-34017.

Smith, A.D., Collaco, R.F. and Trempe, J.P. (2004) AAV vector delivery to cells in culture. In: Gene Delivery to Mammalian Cells Volume 2: Viral Gene Transfer Techniques.  Ed. William Heiser, Humana Press, Totowa, New Jersey, 246:167-178.

Casper, J., Timpe, J., Dignam, J.D. and Trempe, J.P. (2005) Identification of an adeno-associated virus Rep protein binding site in the adenovirus E2a promoter.  J. Virology 79:28-38.

Timpe, J., Bevington, J., Casper, J., Dignam, J.D. and Trempe, J.P. (2005) Mechanisms of adeno-associated virus genome encapsidation.  Current Gene Therapy 5(3):273-285.

Needham, P.G., Casper, J.,  Dignam, J.D. and Trempe, J.P. (2006) Characterization of adeno-associated virus Rep protein-mediated inhibition of transcription of the adenovirus major late promoter in vitro.  J. Virology 80(13):6207-6217.

Timpe, J., Casper, J.M., Verrill, K. and Trempe, J.P. (2006) Effects of adeno-associated virus on adenovirus replication and gene expression during coinfection.  J. Virology 80:7807-7815.

Bevington, J., Needham, P.G., Verrill, K.C., Collaco, R.F., Basrur, V. and Trempe, J.P. (2007) Adeno-Associated Virus Interactions with Nucleophosmin:  Identification of Sub-nucleolar Virion Domains.  Virology 357:102-113.

Timpe, J., Verrill, K.C., Black, D.N., Ding, H-.F. and Trempe, J.P. (2007) Adeno-associated virus induces apoptosis during coinfection with adenovirus.  Virology 358:391-401.

Dignam, S.S., Collaco, R.F., Bieczad, J., Needham, P.G., Trempe, J.P. and Dignam, J.D. (2007) Coupled ATP and DNA binding of adeno-associated virus Rep40 helicase. Biochemistry 46:568-576.

Dignam, S.S., Correiria, J.J., Norcum, M.T., Nada, S.A., Trempe, J.P. and Dignam, J.P. (2007) Activation of the ATPase activity of adeno-associated virus Rep68.  Biochemistry 46:6364-6374.

Bhrigu, V. and Trempe, J.P. (2009) Adeno-associated virus infection of murine fibroblasts with help provided by mouse adenovirus.  Virology (epub ahead of print), PMID #19464040.

Collaco, R., Bevington, J., Bhrigu, V., Kalman-Maltese, V., and Trempe, J.P. (2009) Adeno-associated virus and adenovirus coinfection induces a cellular DNA damage and repair response via redundant phosphatidylinositol 3-like kinase pathways.  Virology, in press.