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Hugh Rosen, M.D., Ph.D.

Professor of Molecular Medicine
Department of Molecular Medicine
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
hrosen@scripps.edu
(858) 784-2396

Scripps Research Joint Appointments

Department of Molecular and Experimental Medicine
Faculty, Graduate Program

Research Focus

Chemical and biological approaches to the molecular mechanisms regulating lymphocyte trafficking

The maintenance of effective host defense depends upon the recirculation of lymphocytes from blood to lymph nodes and returning to blood via lymph. My lab recently described a new molecular mechanism regulating egress of lymphocytes from lymph nodes into lymph and thus blood using reverse pharmacology. A potent compound was identified (FTY720) that induced the disappearance of lymphocytes from peripheral blood. It was phosphorylated to a biologically active and potent molecule that allowed the identification of a molecular target. The mechanism was found to be the activation of a family of G-protein-coupled edg receptors for sphingosine 1-phosphate. We are able to use highly potent picomolar synthetic compounds that activate these receptors at alter lymphocyte trafficking and produce immunosuppression. This mechanism of immunosuppression is of significant interest as a potential novel approach to transplantation rejection and autoimmune diseases including multiple sclerosis. The focus of the laboratory is on using chemical probes of receptor function to elucidate the molecular basis of the control of lymphocyte trafficking, at the level of lymphocytes and endothelial cells, and in the specific tissue microenvironments in lymphoid organs.

Our approaches involve identifying receptors implicated in lymphocyte trafficking, developing chemical agonists and antagonists of receptor function, the evaluation of receptor contribution to cell function in vivo and the identification of transductional and physical changes regulating lymphocyte trafficking in vitro and in intact lymphoid organs by biochemical and imaging methods including confocal scanning microscopy.

These studies are defining fundamental mechanisms of receptors and ligands not previously known to regulate immune function, that may have broad clinical impact.

Education

M.D., Medicine, University of Cape Town, 1982
Ph.D., Physiological Sciences, University of Oxford, 1986

Professional Experience

2007-2017 Professor, Chemical Physiology, The Scripps Research Institute
2002-2007 Professor, Immunology and Microbial Science (IMS), The Scripps Research Institute
2000-2002 Executive Director, Immunology & Rheumatology, Merck & Co., Inc.
1999-2000 Executive Director, Infectious Diseases, Merck & Co., Inc.
1997-1998 Senior Director, Antibiotic Discovery & Development, Merck & Co., Inc.
1994-1997 Director, Antibiotic Discovery & Development, Merck & Co., Inc.
1994-1994 Senior Research Fellow, Inflammation and Immunology, Merck & Co., Inc.
1990-1994 Research Fellow, Inflammation and Immunology, Merck & Co., Inc.

Awards & Professional Activities

Chair, Committee for Advanced Human Therapeutics

Selected References

All Publications

Suzanne Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush E., Xie J., Milligan, J., Thornton, R., Shei, G-J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C., Rupprecht, K., Parsons, W., and Rosen, H. (2002) Alteration of Lymphocyte Trafficking by Sphingosine 1-Phosphate Receptor Agonists. Science 296:346-9. Published online 28 March 2002.

Rosen, H., R. Hajdu, L. Silver, H.Kropp, K. Dorso, J. Kohler, J. G. Sundelof, J. Huber, G. G. Hammond, J. J. Jackson, C. J. Gill, R. Thompson, B. A. Pelak, J. H. Epstein-Toney, G. Lankas, R. R. Wilkening, K. J. Wildonger, T. A. Blizzard, F. P. DiNinno, R. W. Ratcliffe, J. V. Heck, J. W. Kozarich, M. L. Hammond (1999) Reduced Immunotoxicity and Preservation of Antibacterial Activity in a Releasable Side-Chain Carbapenem Antibiotic. Science 283:703-6.

Parent, S.A., T. Zhang, G. Chrebet, J.A. Clemas, D.J. Figueroa, B. Ky, R.A. Blevins, C.P. Austin, and H. Rosen. (2002). Molecular characterization of the murine SIGNR1 gene encoding a C-type lectin homologous to human DC-SIGN and DC-SIGNR. Gene 293:33.

J. Xie, N. Nomura, E. Quackenbush, M. Forrest and H. Rosen (2002) S1P agonists alter trafficking of antigen activated CD4+ T cells (submitted J. Immunol.).