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Michael B.A. Oldstone, M.D.

Professor
Department of Immunology and Microbial Science
California Campus
Laboratory Website
mbaobo@scripps.edu
(858) 784-8054

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Adjunct Professor, Department of Neurosciences, UCSD School of Medicine
Resident Scholar (Professor), University of Alabama College of Arts and Sciences, Tuscaloosa, Alabama

Research Focus

Virus-Immune System Interactions and Viral Pathogenesis

The principle objectives of this laboratory are to understand how viruses cause an acute disease, how the host mounts a defense against the virus, how certain viruses escape from immune recognition and attack, and establish a persistent infection.  Our focus is on how virus affects the lymphoid and central nervous systems and causes disease.  To understand these events we use molecular, cell biologic, and genetic approaches for analysis of virus virulence and for host susceptibility.  We also study how viruses cause immunosuppression on one hand and autoimmunity on the other.

*Pioneered the field of viral immunology and has been a leader in viral pathogenesis and immunity for the past four decades.

*Known for work studying the interaction of the arenavirus lymphocytic choriomeningitis virus with its natural murine host as well as investigations of measles virus and cytokine storm with influenza virus.

*Provided evidence for the concept of viral-induced immunopathology by showing that chronically infected hosts can mount a humoral and cellular immune response to persistent viral infection and such hosts infected early in life were not tolerant to the infecting microbe.

*Showed that persistently infecting viruses can non-cytolytically alter the differentiation or "luxury" function of cells without killing them, a departure from existing dogma that viral diseases reflected destruction of infected cells.

*Provided the evidence and concept for virus-induced autoimmune disease caused by cross-reactive molecular mimics between microbe and host sequences leading to antibody or T cell-induced disease.

*Isolated and characterized immunosuppressive viral variants that co-op host generated negative regulators of the immune response (NIR) that function to keep the immune response in check so it does not harm healthy tissues. By hijacking immunodominant NIR, IL-10 and PD-L1, T cells become exhausted. IFN-1 made within the first 12-18 hrs. of infection by immunosuppressive virus variants was the master regulator of IL-10 and PD-L1, and the disorganizer of secondary lymphoid organs, mechanisms responsible for viral persistence.

Education

M.D., M.D./Ph.D. Program, University of Maryland/Johns Hopkins University, Baltimore, MD, 1959
M.D., Medicine, University of Maryland, Baltimore, MD, 1961

Professional Experience

Internship and Residency:


Intern, Medicine, University Hospital, Baltimore, MD, 1962


Resident, Medicine, University Hospital, Baltimore, MD, 1963-1964


Chief Resident, Neurology, University Hospital, Baltimore, MD, 1965-1966


Research Fellowships:


Department of Surgery (Experimental Pathology), Laboratory of Jacob Fine, Beth Israel Hospital, Boston, MA, 1957


Postdoctoral Fellow, Laboratory of Frank Dixon, Dept. Exp. Pathol., Scripps Clinic & Res. Fdn., La Jolla, CA, 1966-1969


Academic Appointments:


Assistant Member, Dept. Exp. Pathol., Scripps Clinic & Res. Fdn., La Jolla, CA, 1969-1971


Associate Member, Dept. Immunopathology, Scripps Clinic & Res. Fdn., La Jolla, CA, 1972-1976


Member (Professor), Dept. Immunology, Scripps Clinic & Res. Fdn., La Jolla, CA, 1977-1989


Professor, Molecular & Integrative Neurosciences Dept., The Scripps Research Institute, La Jolla, CA, 1989-2008


Professor, Dept. of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA, 2008-present

Awards & Professional Activities

National Academy of Sciences, 2008
Member, National Academy of Sciences, Institute of Medicine, 1996
Excellence in Mentoring Award, American Association of Immunologists, 2011
Pioneer in NeuroVirology Award, International Society for NeuroVirology, 2003
R.E. Dyer Lectureship and Directors Award (NIH) (contributions in viral pathogenesis), 2000
J. Allyn Taylor International Prize in Medicine (host-virus interactions), 1997
Biomedical Science Award, Karolinska Institute, Sweden (contributions virus/autoimmune diseases), 1994
Rous-Whipple Award (contributions in experimental pathology), 1993
Abraham Flexner Award (contributions in biomedical research), 1988
Cotzias Award (contributions in research of CNS), 1986
Burroughs Wellcome Professorship Award to work with J. Skehel, MRC, Mill Hill, UK
Elected Member, Scandinavian Society of Immunology
World Health Organization Committee for the Eradication of Poliomyelitis and Measles Virus
American Association of Physicians
American Clinical and Climatological Association
American Society for Clinical Investigation
Fellow, American Academy of Microbiology
Fellow, American Associaton for the Advancement of Science
Member, National Advisory Committee, The PEW Scholars Program in the Biomedical Sciences
Editor, Virology; Current Topics in Microbiology and Immunology
Editorial Board, Proceedings of the National Academy of Sciences USA; Cell Host & Microbe; Immunity

Selected References

Oldstone, M.B.A.  An odyssey to viral pathogenesis.  Annu. Rev. Pathol. Mech. Dis., in press, 2015. 

Oldstone, M.B.A.  A Jekyll and Hyde profile: Type 1 interferon signaling plays a prominent role in the initiation and maintenance of a persistent virus infection.  J. Infect. Dis., in press, 2015.

Ng, C.T., J.R. Teijaro, A.M. Lee, M. Welch, S. Rice, K.C.F. Sheehan, R.D. Schreiber and M.B.A. Oldstone.  Blockade of interferon beta signaling controls persistent viral infection.  Cell Host & Microbe, in press, 2015. 

Sullivan, B.M., J. Teijaro, J.C. de la Torre and M.B.A. Oldstone.  Early virus-host interactions dictate the course of a persistent infection.  PLoS Pathogens, in press, 2015.

Baccala, R., M. Welch, R. Gonzalez-Quintial, K.B. Walsh, J.R. Teijaro, A. Nguyen, C. Ng, B.M. Sullivan, A. Zarpellon, Z.M. Ruggeri, J.C. de la Torre, A.N. Theofilopoulos and M.B.A. Oldstone.  Type I interferon is a therapeutic target for virus-induced lethal vascular damage.  Proc. Natl. Acad. Sci. USA 111:8925-8930, 2014.  PMCID: PMC4066519

Oldstone, M.B.A.  Molecular mimicry: Its evolution from concept to mechanism as a cause of autoimmune diseases. Monoclonal Antibodies in Immunodiag. Immunotherapy 33:158-165, 2014.  PMCID: PMC4063373

Teijaro, J.R., C. Ng, A.M. Lee, B.M. Sullivan, K.C.F. Sheehan, M. Welch, R.D. Schreiber, J.C. de la Torre and M.B.A. Oldstone.  Persistent LCMV infection is controlled by blockade of type I interferon signaling.  Science 340:207-211, 2013.  PMCID: PMC3640797

Teijaro, J.R., K.B. Walsh, S. Cahalan, D.M. Fremgen, E. Roberts, F. Scott, E. Martinborough, R. Peach, M.B.A. Oldstone and H. Rosen.  Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection.  Cell 146:980-991, 2011.  PMCID: PMC3176439

Oldstone, M.B.A. and K.P. Campbell.  Decoding arenavirus pathogenesis: Essential roles for alpha-dystroglycan-virus interactions and the immune response.  Virology 411:170-179, 2011.  PMCID: PMC3071849

Brooks, D.G., M.J. Trifilo, K.H. Edelmann, L. Teyton, D.B. McGavern and M.B.A. Oldstone.  Interleukin-10 determines viral clearance or persistence in vivo.  Nature Med. 12:1301-1309, 2006.  PMCID: PMC2535582

McGavern, D., U. Christen and M.B.A. Oldstone. Molecular anatomy of antigen-specific CD8+ T cell engagement and synapse formation in vivo.  Nature Immunol. 3:918-925, 2002.  PMCID: PMC2481514

Cao, W., M.D. Henry, P. Borrow, H. Yamada, J.H. Elder, E.V. Ravkov, S.T. Nichol, R.W. Compans, K.P. Campbell and M.B.A. Oldstone.  Identification of α-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus.  Science 282:2079-2081, 1998.