BBS Program
Yale University
P.O. Box 208084
New Haven, CT 06520-8084
Tel: 203.785.3735
Fax: 203.785.3734
bbs@yale.edu
Professor and Head of Neuropathology
B.A. Sarah Lawrence College
M.D. Yale University 1967
The Section of Neuropathology focuses on clinical and experimental models of dementia, with particular emphasis on Transmissible Encephalopathies (TSEs) such as human Creutzfeldt-Jakob disease (CJD) and endemic sheep scrapie. With the dissemination of BSE (“mad cow disease”) worldwide, TSEs have become important for public health. Our goal is to elucidate the molecular and structural nature of the TSE infectious agent, and to delineate how the host responds to to this foreign invader. These responses may be compared to the pathways utilized in pre-senile dementias of unknown etiology, such as Alzheimer’s Disease, to define shared versus unique neurodegenerative mechanisms. Experimental findings in TSEs are most consistent with a causal 25nm viral particle, as first demonstrated here in infectious brain fractions in the 1990s (reviewed in 1). Prion protein amyloid appears late in infection and is probably a pathologic consequence of infection, rather than the causal infectious agent. Recent tissue culture models systems have now additionally shown 25nm dense virus-like particles in situ in infected, but not in uninfected cells (2). These foreign infectious agents provoke host innate immune responses, as do many other covert and latent viruses (reviewed in 1). In contrast, host-encoded prion protein does not. Remarkably, “vaccination” with one agent strain can prevent superinfection by a second TSE agent strain, as shown in animal models, and subsequently in tissue culture experiments (3). All these models can be exploited to clarify critical agent molecules and pathways for improved diagnosis and therapy.
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Yale School of Medicine
Last updated
5/26/08
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