Davies, Brandon - University of Iowa - Department of Biochemistry

个人简介

Education BA, Biology and English, University of Utah PhD, Molecular and Cell Biology, University of California, Berkeley Post Doctoral Fellow, Cardiology, University of California, Los Angeles

研究领域

Our lab studies the role of endothelial cells in lipid metabolism. The lipolytic processing of triglyceride-rich lipoproteins in the bloodstream by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism. Acting inside capillaries, LPL cleaves lipoprotein triglycerides, releasing fatty acids that are taken up by tissues and either used for fuel or stored in cytosolic lipid droplets. LPL is synthesized by parenchymal cells (e.g. myocytes and adipocytes) and secreted into the interstitial spaces, but to be functional in processing triglycerides in the plasma, it must be transported to the capillary lumen. The endothelial cell protein GPIHBP1 serves as the LPL transporter, capturing LPL and moving it across endothelial cells to the capillary lumen. When GPIHBP1 is absent, LPL cannot reach the capillary lumen, leading to severe hypertriglyceridemia (in both humans and mice). The identification of GPIHBP1 as the LPL transporter provided novel evidence that endothelial cells play an active role in plasma lipid metabolism. Maintaining metabolic homeostasis requires moving nutrients, hormones, and enzymes across capillary endothelial cells. Yet, how endothelial cell function is controlled so that metabolic activity inside capillaries and the delivery of nutrients across endothelial cells matches the needs of the underlying tissues has not been adequately explored. To address this issue, we study the mechanisms and regulation of trans-endothelial transport as it relates to lipid metabolism. We also study how the expression of capillary specific proteins, such as GPIHBP1, is controlled in an effort to learn how the metabolic needs of specific tissues influence gene expression in the capillaries servicing those tissues.

近期论文

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Chi, X., Shetty, S. K., Shows, H. W., Hjelmaas, A. J., Malcolm, E. K. & Davies, B. S. (2015). Angiopoietin-like 4 Modifies the Interactions between Lipoprotein Lipase and Its Endothelial Cell Transporter GPIHBP1.. The Journal of biological chemistry, 290(19), 11865-77. DOI: 10.1074/jbc.M114.623769. Beigneux, A. P., Fong, L. G., Bensadoun, A., Davies, B. S., Oberer, M., Gårdsvoll, H., Ploug, M. & Young, S. G. (2014). GPIDeHBP1 Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding.. Circ Res. Young, S. G., Yang, S. H., Davies, B. S., Jung, H. J. & Fong, L. G. (2013). Targeting protein prenylation in progeria. Science translational medicine, 5(171), 171ps3. Jung, H. J., Coffinier, C., Choe, Y., Beigneux, A. P., Davies, B. S., Yang, S. H., Barnes, R. H., Hong, J., Sun, T., Pleasure, S. J., Young, S. G. & Fong, L. G. (2012). Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proceedings of the National Academy of Sciences of the United States of America, 109(7), E423-31. Davies, B. S., Goulbourne, C. N., Barnes, R. H., Turlo, K. A., Gin, P., Vaughan, S., Vaux, D. J., Bensadoun, A., Beigneux, A. P., Fong, L. G. & Young, S. G. (2012). Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells. Journal of lipid research, 53(12), 2690-7. Davies, B. S., Beigneux, A. P., Fong, L. G. & Young, S. G. (2012). New wrinkles in lipoprotein lipase biology. Current opinion in lipidology, 23(1), 35-42. Davies, B. S., Coffinier, C., Yang, S. H., barnes, R. H., Jung, H. J. & young, S. G. (2011). Investigating the purpose of prelamin a processing. Nucleus, 2, 9-Apr. Voss, C. V., Davies, B. S., Tat, S., Gin, P., Fong, L. G., Pelletier, C., Mottler, C. D., Bensadoun, A., Beigneux, A. P. & Young, S. G. (2011). Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 7980-4. Beigneux, A. P., Davies, B. S., Tat, S., Chen, J., Gin, P., Voss, C. V., Weinstein, M. M., Bensadoun, A., Pullinger, C. R., Fong, L. G. & Young, S. G. (2011). Assessing the role of the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) three-finger domain in binding lipoprotein lipase. The Journal of biological chemistry, 286(22), 19735-43. Davies, B. S., Beigneux, A. P., Barnes, R. H., Tu, Y., Gin, P., Weinstein, M. M., Nobumori, C., Nyrén, R., Goldberg, I., Olivecrona, G., Bensadoun, A., Young, S. G. & Fong, L. G. (2010). GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. Cell metabolism, 12(1), 42-52.