Major Areas of Research
- Transmissible spongiform encephalopathies (TSEs), or prion diseases
- Retroviral brain diseases
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.
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.
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 in 1979. Elected as a Fellow in the American Academy of Microbiology, 2011.
James Striebel, M.S., Biologist
Alejandra Rangel, Ph.D., Visiting Fellow
Brent Race, D.V.M., Veterinary Staff Scientist
James Carroll, Ph.D., Staff Scientist
Katie Phillips, B.S., Contract Technician
Tribouillard-Tanvier D, Race B, Striebel JF, Carroll JA, Phillips K, Chesebro B. Early cytokine elevation, PrPres deposition and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes, IL-12p40 and IL-12p35. J Virol. 2012 Jul 11. Epub ahead of print.
Klingeborn M, Race B, Meade-White KD, Chesebro B. Lower specific infectivity of protease-resistant prion protein generated in cell-free reactions. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):E1244-53.
Striebel JF, Race B, Meade-White KD, LaCasse R, Chesebro B. Strain specific resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171. PLoS Pathog. 2011 Sep;7(9):e1002275.
Pathmajeyan MS, Patel SA, Carroll JA, Seib T, Striebel JF, Bridges RJ, Chesebro B. Increased excitatory amino acid transport into murine prion protein knockout astrocytes cultured in vitro. Glia. 2011 Nov;59(11):1684-94.
Klingeborn M, Race B, Meade-White KD, Rosenke R, Striebel JF, Chesebro B. Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol. 2011 Feb;85(4):1484-94.
Chesebro B, Race B, Meade-White K, Lacasse R, Race R, Klingeborn M, Striebel J, Dorward D, McGovern G, Jeffrey M. Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring.PLoS Pathog. 2010 Mar 5;6(3):e1000800.
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.