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University of Nebraska–Lincoln

Nebraska Center for Virology

The Strength of Cooperation Among Three Institutions

Richard A. Bessen, PhD

Associate Professor
Montana State University
Veterinary Molecular Biology

PO Box 173610
Bozeman, MT 59717
Phone – 406.994.1563
Fax – 406.994.4303
rbessen@montana.edu

Research Interests

My lab is investigating agent-host interactions in prion diseases, which are fatal neurodegenerative diseases. These are important diseases of livestock (e.g., scrapie in sheep and bovine spongiform encephalopathy in cattle) and wild cervids (chronic wasting disease) that can be transmitted to humans (variant Creutzfeldt-Jakob disease). Although the majority of prion diseases are due to infection with the prion agent, they can also occur sporadically or as a result of an autosomal dominant mutation. The prion agent appears to be devoid of a nucleic acid genome and consists of a misfolded host protein, called PrP-res, that can further induce its own formation from the normal host prion protein. The multiple etiologies of prion diseases and the unusual nature of the infectious agent is novel in microbiology.

Research in the Bessen lab is investigating (1) the routes of prion neuroinvasion following oral exposure; (2) the mechanism of prion agent entry and spread in nerve cells and skeletal muscle; (3) the host physiological responses during chronic wasting disease infection; and (4) transgenic models of CWD pathogenesis. Currently, there are postdoctoral and technical positions as well as graduate student openings available in the laboratory to pursue these studies.

Selected Publications:

• Bessen, R.A. & Marsh R.F. 1994. Distinct PrP properties suggest the molecular basis for strain variation in transmissible mink encephalopathy. Journal of Virology 68:7859-7868. [abstract]

• Bessen, R.A., Lynch, W.P. & Portis, J.L. 1995. Inhibition of murine retrovirus-induced neurodegeneration in spinal cord by explant. Journal of Virology 69:7300-03. [abstract]

• Race, R.E., Priola, S.A., Bessen, R.A., Ernst, D., Dockter, J., Rall, G.F., Mucke, L., Chesebro, B. & Oldstone, M.B.A. 1995. Neuron specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent. Neuron 15:1183-1191. [abstract]

• Bessen, R.A., Kocisko, D.A., Raymond, G.J. Nandan, S., Lansbury, P.T. & Caughey, B. 1995. Nongenetic propagation of strain specific properties of the scrapie prion protein. Nature 375:698-700. [abstract]

• Bessen, R.A., Raymond, G.J. & Caughey, B. 1997. In situ formation of the scrapie prion protein in transmissible spongiform encephalopathy infected brain slices. Journal of Biological Chemistry 272:15227-31. [abstract]

• Raeber A.J., Race R.E., Brandner S., Priola S.A., Sailer A., Bessen R.A., Mucke L., Manson J., Aguzzi A., Oldstone M.B.A., Weissmann C., & Chesebro B. 1997. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J. 16:6057-65. [abstract]

• Caughey B., Raymond G.R. & Bessen R.A. 1998. Strain-dependent differences in beta-sheet conformations of abnormal prion protein. Journal of Biological Chemistry 273:32230-35. [abstract]

• Bartz, J.C., Bessen, R.A., McKenzie, D., Marsh, R.F. & Aiken, J.M. 2000. Adaptation and selection of prion protein strain conformations following interspecies transmission of transmissible mink encephalopathy. Journal of Virology 74:5542-47. [abstract]

• Bartz, J.C., Kincaid, A.E. & Bessen, R.A. 2002. Retrograde transport of transmissible mink encephalopathy within descending motor tracts. Journal of Virology 76:5759-5768.
[abstract]

• Bartz, J.C., Kincaid, A.E. & Bessen, R.A. 2003. Rapid prion neuroinvasion following tongue infection, Journal of Virology 77:583-591. [abstract]

• Bartz, J.C., Aiken, J.M. & Bessen, R.A. 2004 Delay in onset of prion disease for the HY Strain of transmissible mink encephalopathyas a result of prior peripheral inoculation with the replication-deficient DYstrain. Journal of General Virology 85:265-273 [abstract]

• Mulcahy, E.R. & Bessen, R.A. 2004. Strain-specific kinetics of prion protein formation in vitro and in vivo. Journal of Biological Chemistry 279:1643-1649. [abstract]

• Mulcahy, E.R, Bartz, J.C., Kincaid, A.E. & Bessen, R.A. 2004. Prion infection of skeletal muscle cells and papillae in the tongue, Journal of Virology 77:583-591. abstract

Education:

Ph.D. - University of Wisconsin,
   1991, Veterinary Science

M.S. - University of Wisconsin, 1987, Veterinary Science

B.S. - Washington University,
1984, Biology

Professional Experience:

2003-present
Associate Professor, Veterinary Molecular Biology, Montana State University

2003
Associate Professor, Medical Microbiology & Immunology, Creighton University School of Medicine

2000- present
Faculty, Nebraska Center for Virology

1997-2003
Assistant Professor, Medical Microbiology & Immunology, Creighton University School of Medicine

1996- 1997
European Molecular Biology Organization Postdoctoral fellow, Neuropathogenesis Unit, Institute for Animal Health, Scotland

1992- 1996
Postdoctoral fellow, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases

1992
Postdoctoral fellow, University of Wisconsin-Madison

Extramural Grant Support:

Oral prion neuroinvasion via cranial nerves, United States Department of Agriculture, National Research Initiative Competitive Grants Program, 9/15/02 to 9/14/05.

Routes of prion neuroinvasion following oral infection, National Institute of Allergy & Infectious Diseases, 6/1/03 to 5/31/07.

Chronic Wasting Disease Research Initiative, U.S. Fish & Wildlife Service, 8/1/03 to 7/31/08

Identification of preclinical markers for Chronic Wasting Disease, U.S. Geological Survey, 4/1/04 to 2/28/07.

Honors and Awards:

1996 – 97 European Molecular Biology Organization Fellowship Award

1998 – 01 Health Future Foundation Faculty Development Award

1999 – 00 USDA Panel Member Review, Animal Health and Well-being (Virology)

2000 Young Investigator Award, Creighton University School of Medicine