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Molecular Medicine

Faculty

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

Professor of Molecular Medicine
Department of Molecular Medicine
California Campus
Laboratory Website
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

Awards & Professional Activities

Chair, Committee for Advanced Human Therapeutics

Selected References

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.).

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty