Bruce W. Chesebro, M.D.

Chief, Laboratory of Persistent Viral Diseases
Chief, TSE/Prion and Retroviral Pathogenesis Section

Dr. Chesebro received his M.D. from Harvard Medical School in 1968. He completed postdoctoral studies at Karolinska Institute, 1967; Stanford University, 1968-1970; and National Institute of Arthritis and Metabolic Diseases, 1970-1972. He came to the Rocky Mountain Laboratories in 1972 and became the chief of the Laboratory of Persistent Viral Diseases in 1979.

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.

Description of Research Program

Research is aimed at studying the pathogenesis of transmissible encephalopathies or prion diseases as well as murine and human retroviral diseases of the brain. These diseases are being studied at the biochemical, cellular, and whole animal model levels. 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 which lack expression of important cytokine and chemokine genes and their receptors are also used for pathogenesis studies. Similar approaches have been used for retroviral envelope mutants, which differ in their pathogenic properties.

Recently, together with collaborators at the Scripps Research Institute in La Jolla, our group developed a transgenic mouse model expressing anchorless prion protein. This model replicated the prion/TSE agent and has extensive amyloid deposits in brain, but develops minimal clinical disease. This model has become an interesting new tool for studies of prion disease pathogenesis.

Research Group Members

Rachel LaCasse, Ph.D., Senior Research Associate; Lisa Kercher, Ph.D., Postdoctoral Fellow; Brandon Walter, Ph.D., Postdoctoral Fellow; Richard Race, D.V.M., Senior Investigator; Brent Race, D.V.M., Veterinary Staff Scientist; Kimberly Meade-White, M.S., Biologist; Melissa Pathmajeyan, Graduate Student.

Selected Recent Publications

Chesebro B. Introduction to the transmissible spongiform encephalopathies or prion diseases. Br Med Bull. 2003. 66: 1-20. 

Jeffrey M, Goodsir CM, Race R, Chesebro B. Scrapie-specific neuronal lesions are independent of neuronal PrP expression. Ann Neurol. 2004. 55: 781-792.

Kercher L, Favara C, Chan C-C, Race R, Chesebro B. Differences in scrapie-induced pathology of the retina and brain in transgenic mice that express hamster prion protein in neurons, astrocytes, or multiple cell types. Am J Path. 2004. 165: 2055-2067.

Peterson KE, Hughes S, Dimcheff DE, Wehrly K, Chesebro B. Separate sequences in a murine retroviral envelope protein mediate neuropathogenesis by complementary mechanisms with differing requirements for tumor necrosis factor alpha. J Virol. 2004. 78: 13104-13112.

Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E, Oldstone M. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science. 2005. 308: 1435-1439.

Walter BL, Wehrly K, Swanstrom R, Platt E, Kabat D, Chesebro B. Role of low CD4 levels in the influence of human immunodeficiency virus type 1 envelope V1 and V2 regions on entry and spread in macrophages. J Virol. 2005. 79: 4828-4837.

Criado JR, Sanchez-Alavez M, Conti B, Giacchino JL, Wills DN, Henriksen SJ, Race R, Manson JC, Chesebro B, Oldstone MB. Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons. Neurobiol Dis. 2005. 19: 255-265.

Peterson K, Chesebro B. Influence of proinflammatory cytokines and chemokines on the neuropathogenesis of oncornavirus and immunosuppressive lentivirus infections. CTMI. 2006. 303: 67-95.

back to top