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Richard A. Bessen, PhD
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 encephalopathy
as a result of prior peripheral inoculation with the replication-deficient DY
strain. 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
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