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Molecular Medicine

Faculty

Richard Milner, M.D., Ph.D.

Associate Professor of Molecular Medicine
Department of Molecular Medicine
California Campus
rmilner@scripps.edu
(858) 784-8569

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Regulation of Cerebral Angiogenesis by the Extracellular Matrix

The goal of our research is to understand how extracellular matrix (ECM) proteins regulate blood vessel growth in the central nervous system (CNS). During development, endothelial cells switch from an angiogenic phenotype into a stable differentiated phenotype, and this coincides with a switch in expression, from fibronectin receptors during angiogenesis, to laminin receptors in the adult. In vitro studies reveal that fibronectin strongly promotes brain endothelial cell survival and proliferation, and that this effect is mediated via the fibronectin receptors, α5β1 and αvβ3 integrins. To examine whether angiogenesis in the adult CNS is also associated with induction of fibronectin and its receptors we examined this process in a mouse model of hypoxia. In the hypoxic CNS, fibronectin and the α5β1 integrin were strongly upregulated on angiogenic vessels, suggesting that the α5β1 integrin may be important in driving angiogenesis in the adult CNS. Currently we are using knockout mice and a combination of in vivo and in vitro approaches to define the roles of the α5β1 and αvβ3 integrins at specific stages of cerebral angiogenesis.

Education

Ph.D., Developmental Neurobiology, University of Cambridge, 1994
M.D., Medicine and Surgery, University of Cambridge, 1998
B.S., Physiology, University of Leeds, 1990

Awards & Professional Activities

2004 - Wellcome Trust Career Development Fellowship (University of Cambridge)
2006 - Harry Weaver Neuroscience Scholar Award from The National Multiple Sclerosis Society (one of only two awarded nationwide in 2006)

Selected References

Milner, R., Crocker S.J., Hung, S., Wang, X., Frausto, R.F. & del Zoppo G.J. (2007) Fibronectin and vitronectin induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins α5β1 and α5β1. J. Immunol. 178, 8158-8167.

Milner, R., Hung, S., Wang, X., Berg, G. & del Zoppo, G.J. (2008). Responses of endothelial cell and astrocyte matrix-integrin receptors to ischemia mimic those observed in the neurovascular unit. Stroke. 39, 191-7.

Milner, R., Hung, S., Wang, X., Spatz, M. & del Zoppo, G.J. (2008). The rapid decrease in astrocyte-associated dystroglycan expression by focal cerebral ischemia is protease-dependent. J. Cereb. Blood Flow Metab. 28, 812-23.

Milner, R., Hung, S., Erokwu, B., Dore-Duffy, P., LaManna, J.C., & del Zoppo, G.J. (2008). Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia. Mol. Cell. Neurosci. 38, 43-52.

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