Steven A. Hoffman
Research
Scientific
Our research focuses on the interactions and relations between mind, brain and the immune system. This includes biomedical research into how the immune system can lead to neuropsychiatric manifestations. The primary focus is on CNS lupus, but there are implications for diseases such as multiple sclerosis, myasthenia gravis and rheumatoid arthritis. The research also investigates how the central nervous system (CNS) can contribute to an autoimmune state; how psychosocial factors influence the immune system (e.g., how stress affects the immune system); and the neuro-immunological circuitry (viz., interconnections between the brain and immune system). Some questions addressed are: How do psychosocial factors contribute to an autoimmune disease? How does the immune system signal the brain? What are the mechanisms leading to CNS lupus?
More specifically, we are currently pursuing two areas of scientific research: (1) The role of brain reactive autoantibodies (and immune assault in general) in causing mental disorders, particularly in autoimmune mediated diseases, e.g., systemic lupus erythematosus. Our methodology uses cell culture, hybridoma technology, monoclonal antibodies, ELISA, immunoblotting, gel electrophoresis, immunohistochemistry, as well as behavioral and neuroscience techniques; (2) Neural modulation of tolerance and autoimmune states, with a focus on the role of substance P, using the techniques of flow cytometry, cell culture, etc. We are also interested in, and have done research on, the relation between psychosocial factors and the immune system in autoimmune disease, as well as computer models of the immune system.
Philosophic
Our studies also take us into the interface between philosophy and science. This examines some of the foundations for the research we do in our laboratory. Our current research in this area focuses on psychoneuroimmunology and the mind-brain relation. What are the theoretical foundations of PNI? Do they favor one theory of the mind-brain relation over another (e.g., dualistic interactionism vs. materialist identity theory)? Other topics of interest include philosophy of immunology, philosophy of mind (concepts of self and the mind-brain relation), biomedical ethics, science and religion, the nature of scientific inquiry (focusing on theoretical frameworks and constructs).
Current Students
Graduate Students
Stephanie Williams
Undergraduate Students
Brian Johnson
Beenish Majeed
Elisa Shoff
Selected Publications
Zameer, A. and Hoffman , S.A. , B and T cells in the brains of autoimmune mice, J. Neuroimmunol. 146: 134-140, 2004 (PDF)
Ballok, D.A., Earls, A.M., Krasnik, C., Hoffman , S.A. and Sakic, B., Autoimmunity-induced damage of the midbrain dopaminergic system in lupus-prone mice, J. Neuroimmunol. 152: 83-97, 2004
Zameer, A. and Hoffman , S.A. , Increased ICAM-1 and VCAM-1 expression in the brains of autoimmune mice, J. Neuroimmunol. 142:67-74, 2003 (PDF)
Zameer, A. and Hoffman , S.A. , Immunoglobulin binding to brain in autoimmune mice, J. Neuroimmunol. 120: 10-18, 2001 (PDF)
Hoffman , S.A. , Harbeck, R.J. and Shucard, D.W. The immune system can affect learning: Chronic immune complex disease in a rat model. J. Neuroimmunol. 86:163-170, 1998 (PDF)
Crimando, J., Cooper, K. and Hoffman , S.A. Inhibition of sodium channel currents by antineuronal autoantibody from autoimmune mic. Ann. N.Y.A.S. 823:303-307, 1997
Crimando, J. and Hoffman , S.A. Characterization of brain-reactive monoclonal IgG autoantibodies. Brain Behav. Immun. 9:165-181, 1995.
Khin, N.A and Hoffman , S.A. Brain-reactive monoclonal autoantibodies: Production and characterization. J. Neuroimmunol., 44:137-148, 1993.
Bartholomew, S.A and Hoffman, S.A. Effects of peripheral cytokine injections on multiple unit activity in the anterior hypothalamic area of the mouse. Brain Behav. Immun. 7:301-316. 1993 (PDF)
Maag, T.J. and Hoffman , S.A. Anti-brain antibodies in the sera of rheumatoid arthritis patients: Relation to disease activity and psychological status. J. Neuroimm. 45:37-46, 1993
Harrington, L., Affleck, G., Urrows, S., Tennen, H., Higgins, P., Zautra, A. and Hoffman, S. Temporal covariation of soluble interleukin-2 receptors, daily stress, and disease activity in rheumatoid arthritis. Arth. Rheum. 36:199-203, 1993
Schiffer, R.B. and Hoffman , S.A. Behavioral sequelae of autoimmune disease. Review in: Psychoneuroimmunology II, Ader, R., ed., Academic Press, N.Y., 1991
Hoffman , S.A. and Madsen, C.S. Brain specific autoantibodies in murine models of systemic lupus erythematosus. J. Neuroimmunol. 30:229-237, 1990
Narendran, A. and Hoffman , S.A. Characterization of brain reactive autoantibodies in murine models of systemic lupus erythematosus. J. Neuroimm. 24:113-123, 1989
Hoffman , S.A. , Narendran, A., Shucard, D.W. and Harbeck R.J. Autoantibodies, immune complexes and behavioral disorders: Neuropsychiatric involvement in systemic lupus erythematosus. Drug Dev. Res., 15:237-251, 1988
Narendran, A., and Hoffman , S.A. Identification of autoantibody reactive integral brain membrane antigens -- A two dimensional analysis. J. Immunol. Meth. 114: 227-234, 1988
Hoffman , S.A. , Arbogast, D.N., Ford, P.M., Shucard, D.W., & Harbeck, R.J. Brain reactive autoantibody levels, as a function of age, in the sera of autoimmune mice. Clin. Exp. Immunol. 70: 74-83, 1987
Hoffman , S.A. , Arbogast, D.N., Biundo, T.T., Shucard, D.W., and Harbeck, R.J. Permeability of the blood cerebrospinal fluid barrier during acute immune complex disease. J.Immunol. 130:1695-1698, 1983
Hoffman , S.A. , Shucard, D.W., Brodie, H.A., Reinfenrath, C., and Harbeck, R.J. Suppression of water intake by immune complex formation in the hypothalamus: Implications for systemic lupus erythematosus. J. Neuroimmunol. 2: 167-176, 1982
Manuscripts in Preparation
Williams, S., Sakic, B., and Hoffman, S.A., Circulating Brain-Reactive Autoantibodies and Behavioral Deficits (manuscript in preparation, 2009).
Hoffman , S.A. The immunologic self: Perspectives on philosophic concepts of self
Hoffman , S.A. and Ching, P. Increased expression of MHC class I in MRL/lpr mice
Book Chapters
Hoffman, S.A., and Sakic, B., Autoimmunity and Brain Dysfunction, In: The Neuroimmunological Basis of Behavior and Mental Disorders, Eds. Siegel, A., and Zalcman, S., Springer Science, 2008.
Hoffman , S.A. and Harbeck, R.J. CNS Lupus and the Blood Brain Barrier. In: Implications of the Blood Brain Barrier and its Manipulation, Vol. 2, Neuwelt, E., ed., Plenum, N.Y., 1989.
Schiffer, R.B. and Hoffman , S.A. Behavioral sequelae of autoimmune disease. In: Psychoneuroimmunology II, Ader, R., ed., Academic Press, N.Y., 1991.