department of developmental biology

Professor

Department of Developmental Biology

Research Interests

Research in this laboratory focuses on CNS (brain and spinal cord) inflammation and pathogenesis in a mouse model of multiple sclerosis. We have used genetically marked lymphocytes to study the mechanisms of their entry into the CNS to cause disease. We have found that the initial compromise of the blood brain barrier requires that lymphocytes “see” a CNS antigen in the space between blood vessels and the parenchyma (body) of the CNS. This interaction initiates a “conversation” between cells originating in the blood and cells of the parenchyma itself that determines whether or not inflammatory invasion will occur.

The molecular language of this “conversation” is a group of small proteins (cytokines and chemokines) that regulate the expression of adhesion molecules (VCAM-1) on astrocytes in the parenchyma and recruit macrophages and other inflammatory cells. The VCAM-1 expression on astrocytes appears to be an important mechanism to allow both the recruitment and retention of the inflammatory infiltrate into the parenchyma, causing demyelination and axon loss associated with paralysis.

We have developed a novel technique to isolate the infiltrating lymphocytes at various stages of invasion. Current experiments are focused on understanding the molecular changes in the lymphocytes as they invade the CNS to identify possible targets for preventing their invasion of the CNS. We are also focusing on the role of the astrocyte in both promoting and protecting from or healing the inflammatory process. Our results suggest that there may be regionally specific “dialects” of the conversation making some CNS regions more susceptible to invasion than others and astrocytes are an important part of those regional differences.

Russell Biosketch

Academic Positions:

• 1996-present, Professor of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO
• 1984-1996, Associate Professor of Pharmacology, Washington University School of Medicine, St. Louis, MO
• 1978-1984, Assistant Professor of Pharmacology, Washington University School of Medicine, St. Louis, MO
• 1974-1978, Postdoctoral Fellow, Laboratory of Herman Eisen, Massachusetts Institute of Technology, Cambridge, MA
  

Honors:

• Helen Hay Whitney Postdoctoral Fellowship, 1975-1978
• Research Career Development Award, DHHS 1984-1989
• Outstanding Mentor Award from Graduate Student Senate, 2000
• Mentor Award from Academic Women’s Network, 2000
  

Review Panels:

• Member of American Association of Immunologists
• Workshop Chairman, "T-cell Lytic Mechanisms," International Cytotoxicity Workshop, Arolla, Switzerland, 1987
• Minisymposium Chairman, "Mechanisms of Cytotoxicity," FASEB, 1988
• Workshop Chairman, "Regulation of Peripheral Immune Responses", Keystone Symposium, 1996
• Member, NSF Cellular Physiology Advisory Panel, 1987-1990
• Member, NIH Experimental Immunology Study Section, 1991-1995
• Member, AAMC GREAT Group (graduate Deans), 1997-present
• Ad Hoc Reviewer, Journal of Immunology
• Ad Hoc Reviewer, Journal of Biological Chemistry
• Ad Hoc Reviewer, FASEB Journal
• Ad Hoc Reviewer, Journal of Immunopharmacology
• Ad Hoc Reviewer, Science
• Ad Hoc Reviewer, Cell
  

Selected Publications

Sabelko-Downes, K. A., M. T. Gimenez, G. C. Suvannavejh, S. D. Miller and J. H. Russell. (2000) Genetic control of pathogenic mechanisms in autoimmune demyelinating disease. J. Neuroimmunol.110:168.

Shenoy, S., T. Mohanakumar, T. Chatila, J. Tersak, B. Duffy, R. Wang, A. R. B. Thilenius and J. H. Russell. (2001) Defective apoptosis in Lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias. Clin. Immunol. 99: 266.

Hurov, J. B., T. S. Steppenbeck, C. M. Zmasek, L. S. White, J. H. Russell, A. C. Chan, K. M. Murphy and H. Piwnica-Worms. (2001) Immune system dysfunction
and autoimmune disease in mice lacking Emk (Par-1) protein kinase. Mol. Cell. Biol. 21:3206.

Nguyen, T. and J. H. Russell. (2001) The regulation of FasL expression during activation-induced cell death (AICD). Immunol. 103:426.

Song, S. K., S. W. Sun, M. J. Ramsbottom, C. Chang, J. H. Russell and A. H. Cross. (2002) Dysmelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17:1429.

Watanabe, N., M. Gavrieli, J.R. Sedy, J. Yang, F. Fallarino, S.K. Loftin, M.A. Hurchla, N. Zimmerman, J. Sim, X. Zang, T.L. Murphy, J.H. Russell, J.P. Allison and K.M. Murphy. (2003) BTLA, and inhibitory receptor in lymphocytes with similarities to CTLA-4 and PD-1. Nat. Immunol. 4:670.

Yu, J.J., C.S.Tripp and J.H. Russell. (2003) Regulation and Phenotype of an innate Th1 Cell; Role of cytokines and the p38 kinase pathway. J. Immunol. 171:6112.

Gimenez, M.A., J.E. Sim and J.H. Russell. (2004) TNFR1-Dependent Parenchymal VCAM-1 Expression Lays Down the Path for Destructive CNS Inflammation. J. Neuroimmunol. 151(1-2):116-25.

Gimenez, M.A., J.E. Sim, A.H. Cross and J.H. Russell. Fas-dependent demyelination and axonal loss is responsible for chronic disease in the C57BL/6 MOG model of EAE. (manuscript submitted).

Archambeault, A.S., J.E. Sim, M.A. Gimenez, J.H. Russell. T cell trafficking into the CNS Parenchy requires permeabilization of the blood brain barrier by activated T cells recognizing CNS antigens. (manuscript submitted).

Archambault AS, Sim J, McCandless EE, Klein RS, Russell JH. Region-specific regulation of inflammation and pathogenesis in experimental autoimmune encephalomyelitis. J Neuroimmunol 2006 181:122-132.

Gimenez MA, Sim J, Archambault AS, Klein RS, Russell JH. A TNFR1-dependent conversation between CNS-specific T cells and the CNS is required for inflammatory infiltration of the spinal cord. Am J Pathol 2006 168:1200-1209.

Lees JR, Archambault AS, Russell JH. T-cell trafficking competence is required for CNS invasion. J Neuroimmunol 2006 177:1-10.

Archambault AS, Sim, J Gimenez MA, Russell JH. Defining Antigen Dependent Stages of T cell Migration from the Blood to the Central Nervous System Parenchyma. Eur J Immunol 2005 35:1076-1085.

Gimenez MA., Sim J, Russell JH. TNFR1-Dependent Parenchymal VCAM-1 Expression Lays Down the Path for Destructive CNS Inflammation. J Neuroimmunol 2004 151:116-125.

Contact Information

John Russell
Department of Developmental Biology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 362-2556
jrussell@wustl.edu