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Bourne, Henry
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Differentiated HL-60 cells polarized in response to chemoattractant. F-actin (red) and phosphorylated myosin light chain (green) accumulate at the front and back, respectively
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| Research Statement | | Dr. Bourne received his MD degree from Johns Hopkins and took his postdoctoral training at the National Institutes of Health and UCSF. He came to UCSF in 1969, became a faculty member in the Department of Medicine in 1971, and served as chair of the Department of Pharmacology from 1984 to 1992.
Dr. Bourne’s research for many years focused on trimeric G proteins and G protein coupled receptors. During the past five years he has turned his laboratory’s efforts toward dissecting the cellular signals responsible for polarity and direction-finding (chemotaxis) of human leukocytes. Using HL-60 leukemia cells, which can be induced to differentiate into mature neutrophils, Dr. Bourne’s laboratory has shown that attractants trigger polarity by activating opposed “frontness” and “backness” signaling pathways, mediated by different trimeric G proteins and Rho GTPases. These pathways trigger different actin assemblies, which then ‘self-organize’ to create cellular polarity. This polarity is apparently distinct from the neutrophil ‘compass’, which senses and interprets attractant gradients to orient the direction of polarity. At present the laboratory is focusing on the compass mechanism, using drugs, toxins, and RNAi to alter functions of candidate compass components and assessing their effects in attractant gradients created by micropipettes or in microfluidic devices, which create instantaneous, stable gradients of any desired slope or concentration. |
Publications | | Servant, G., O.D. Weiner, P. Herzmark, T. Balla, J.W. Sedat, and H.R. Bourne, Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science (2000) 287:1037-1040.
Weiner, O.D., P.O. Neilsen, G.D. Prestwich, M.W. Kirschner, L.C. Cantley, and H.R. Bourne, A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nat Cell Biol (2002) 4(7):509-513.
Wang, F., P. Herzmark, O.D. Weiner, S. Srinivasan, G. Servant, and H.R. Bourne, Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat Cell Biol (2002) 4(7):513-518.
Srinivasan, S., F. Wang, S. Glavas, A. Ott, F. Hofmann, K. Aktories, D. Kalman, and H.R. Bourne, Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J Cell Biol (2003) 160:375-385.
Xu, J., F. Wang, A. Van Keymeulen, P. Herzmark, A. Straight, K. Kelly, Y. Takuwa, N. Sugimoto, T. Mitchison, and H.R. Bourne, Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell (2003) 114:201-214. |
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