Bruce W. Chesebro, M.D.

Research is aimed at studying the pathogenesis of transmissible encephalopathies or prion diseases. These diseases are being studied at the biochemical, cellular, and whole animal model levels. We are currently studying both chronic wasting disease (CWD) of deer and elk as well as rodent-adapted sheep scrapie. Rodent and nonhuman primate models are being used for CWD. Mutant prion protein (PrP) molecules have been expressed in neural cell cultures and in transgenic mice to study the effects of PrP alterations on agent replication and disease development. Knockout mice that lack expression of important cytokine and chemokine genes and their receptors are also used for pathogenesis studies.

Figure shows protease-resistant prion protein (PrP-res) deposited as amyloid stained with Thioflavin S in the corpus callosum and cerebellum of an anchorless PrP transgenic mouse 194 days after infection with scrapie strain 22L. Adapted from Chesebro et al. Science 308:1435-39, 2005.

Credit: NIAID

Our group also studies a transgenic mouse model expressing anchorless prion protein. This model replicates the prion/TSE agent and has extensive amyloid deposits in the brain with cerebral amyloid angiopathy similar to human brain amyloid diseases including Alzheimer’s disease. This model mimics a new fatal familial prion disease in which patients express prion protein with a stop codon near the C-terminus, thus eliminating the GPI anchoring of prion protein.