Bruce W. Chesebro, M.D.

TSE/Prion and Retroviral Pathogenesis Section

Bruce W. Chesebro, M.D.

Chief, TSE/Prion and Retroviral Pathogenesis Section

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Bruce W. Chesebro, M.D.
  • Transmissible spongiform encephalopathies (TSEs), or prion diseases
  • Retroviral brain diseases

Program Description

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.

Protease-resistant prion protein (PrP-res)

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 alScience 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.

Biography

Education

M.D., 1968, Harvard Medical School

Dr. Chesebro received his M.D. from Harvard Medical School in 1968. He completed postdoctoral studies at the Karolinska Institute, Sweden, in 1967; at Stanford University from 1968 to 1970; and at the National Institute of Arthritis and Metabolic Diseases from 1970 to 1972. He came to NIAID in 1972 and became chief of the Laboratory of Persistent Viral Diseases (now Laboratory of Neurological Infections and Immunity) in 1979. Elected as a Fellow in the American Academy of Microbiology, 2011.

Selected Publications

Carroll JA, Race B, Williams K, Striebel J, Chesebro B. Microglia are Critical in Host Defense Against Prion Disease. J Virol. 2018 May 16. pii: JVI.00549-18. doi: 10.1128/JVI.00549-18 PMID: 29769333

Carroll JA, Chesebro B. Neuroinflammation, Microglia, and Cell-Association during Prion Disease. Viruses. 2019 Jan 15;11(1). pii: E65. doi: 10.3390/v11010065. Review. PMID: 30650564

Race B, Williams K, Chesebro B. Transmission Studies of Chronic Wasting Disease to Transgenic Mice Overexpressing Human Prion Protein using the RT-QulC Assay. Vet Res. 2019 Jan 22;50(1):6. doi: 10.1186/s13567-019-0626-2. PMID: 30670087

 Carroll JA, Race B, Williams K, Striebel J, Chesebro B.  RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection. Mol Brain. 2020 May 7;13(1):71. doi: 10.1186/s13041-020-00610-8.PMID: 32381108

Race B, Williams K, Striebel JF, Chesebro B. Prion-associated cerebral amyloid angiopathy is not exacerbated by human phosphorylated tau aggregates in scrapie-infected mice expressing anchorless prion protein. Neurobiol Dis. 2020 Oct;144:105057. doi: 10.1016/j.nbd.2020.105057. Epub 2020 Aug 21. PMID: 32829029

Striebel JF, Race B, Leung JM, Schwartz C, Chesebro B. Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses.  Acta Neuropathol Commun. 2021 Jan 29;9(1):17. doi: 10.1186/s40478-021-01120-x.PMID: 33509294

Visit PubMed for a complete publication list.

Patents

Robertson MN, Chesebro B, Miyazawa M, Britt WJ, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Monoclonal antibodies for detection of friend murine leukemia virus. United States patent US 6,403,300. 11 Jun 2002.

Chesebro BW, Caughey BW, Chabry J, Priola S, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Inhibitors of formation of protease resistant prion protein. United States patent US 6,355,610. 12 Mar 2002.

Chesebro BW, Caughey BW, Chabry J, Priola S, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Inhibitors of formation of protease resistant prion protein. United States patent US 6,211,149. 3 Apr 2001.

Chesebro B, Wehrly K, inventors; The United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Cell lines useful for detection of human immunodeficiency virus. United States patent US 5,811,282. 22 Sep 1998.

Research Group

James Striebel, M.S., Senior Research Biologist
James Carroll, Ph.D., Staff Scientist

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