Biography
Dr Bensadoun's professional expertise is in lipid transport and more specifically in the biochemistry, structure and function of lipolytic enzymes(lipoprotein lipase and hepatic lipase) and lipase-binding proteins such as heparan sulfate proteoglycans(syndecans and glypicans) and GPIHBP1 (glycosylphosphatidylinositol anchored HDL binding protein).
Work in my laboratory is mainly concerned with molecular aspects of lipid transport, the study of how lipids are transported between various organs in the body. More specifically our work is concerned with the characterization and regulation of lipases and their receptors, proteins that play major roles in removing lipids from blood. Lipases degrade triglycerides and phospholipids in blood and control the removal of cholesterol from plasma. Our effort has concentrated on two enzymes, lipoprotein lipase(LPL) and hepatic lipase(HL) and the major receptors for these enzymes, syndecans and glypicans, two classes of proteoglycans and a newly discovered receptor, GPIHBP1 (glycosylphosphatidyl inositol anchored HDL binding protein). Lipases because of their impact on plasma triglycerides and cholesterol concentrations play a major role in arterial wall plaque formation and the atherosclerotic process. We are currently focusing our efforts on studies of the structure, molecular mechanism and function of glycosylphosphatidylinositol-HDL-binding protein 1(GPIHBP1). GPIHBP1 is a newly discovered protein which is essential to normal metabolism of triglyceride-rich lipoproteins. Mice deficient in GPIHBP1 develop gross hypertriglyceridemia with plasma concentration in excess of 3000 mg triglyceride /100ml. Recent results suggest that lipoprotein lipase (LPL), the enzyme responsible for triglyceride hydrolysis is mis-localized in GPIHBP1 deficient mice. Light microscopy experiments show that the enzyme is located in the basement membrane instead of its typical location on the luminal surface of the endothelium. In vitro transport experiments with cultured endothelial cells in trans-well dishes demonstrate that cells expressing GPIHBP1 transport LPL from the basal lateral surface to the apical surface. We are currently exploring the molecular mechanisms underlying this property of GPIHBP1 in trans-endothelial transport. Thiswork is being carried out in collaboration with Dr Stephen Young’s group in department of cardiology at UCLA.
Franssen, R., Young, S.G., Peelman, F., Hertecant, J., Sierts, J.A., Schimmel,A.W.M., Bensadoun, A., Kastelein, J.J.P., Fong, L.G., Dallinga-Thie, G.M., Beigneux, A.P. Chylomicronemia with low postheparin lipoprotein lipase levels in the setting of GPIHBP1 defects. Circ. Cardiovasc. Genet. 3:169-178, 2010.
Weinstein, M.M., Beigneux, A.P., Davies, B.S., Gin,P., Voss, C., Walzem, R.L., Reue, K., Tontonoz, P., Bensadoun, A., Fong, L.G., Young, S.G. Cholesterol Intake modulates plasma triglyceride levels in GPIHBP1-deficient mice. Arteriosler. Thromb. Vasc. Biol. 30:2106-2013, 2010.
Olafsen,T., Young, S.G., Davies, B.S., Beigneux, A.P., Davies, B.S., Kenanova, V.E., Voss, C., Young, G., Wong, K.P., Barnes R.H.2nd, Tu, Y., Weinstein, M.M., Nobumori, C., Huang, S.G., Goldberg, I.J., Bensadoun, A., Wu, A.M., Fong, L.G. Unexpected expression pattern for glycosylphosphatidylinositol-anchored HDL-binding protein1 (GPIHBP1) in mouse tissues revealed by positron emission tomography scanning. J.Biol.Chem. 285: 39239-39248, 2010.
Bishop, J.R., Passos-Bueno, M.R., Fong, L., Stanford, K.I., Gonsales, J.C., Yeh, E., Young, S.G., Bensadoun, A., Witztum, J.L., Esko, J.D., Moulton, K.S. Deletion of the basement membrane heparin sulfate proteoglycan type XVIII collagen causes hypertriglyceredemia in mice and humans. PLoS One. 5:e13919, 2010.
Davies, B.S., Beigneux, A.P., Barnes, R.H.2nd, Tu,Y., Gin, P., Weinstein, M.M., Nobumori, C., Nyren, R., Goldberg, I., Olivecrona, G., Bensadoun, A., Young, S.G., Fong, L.G. GPIHBP1 is responsible for the entry of lipoprotein lipase in capillaries. Cell Metab. 12: 42-52, 2010.
Gin,P., Beigneux, A.P., Voss, C., Davies, B.S., Beckstead, J.A., Ryan, R.O., Bensadoun, A., Fong, L.G., Young, S.G. Binding preferences for GPIHBP1, a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells. Aterioscler. Thromb. Vasc. Biol. 31: 176-182, 2011.
Young, S.G., Davies, D.S., Voss, C.V., Gin, P., Weinstein, M.M., Totonoz, P., Reue, K., Bensadoun, A., Fong, L.G. GPIHBP1, an endothelial cell transporter for lipoprotein lipase. J.Lipid Res. 52: 1869-1884, 2011.
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. Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1. Proc. Natl. Acad. Sci. USA, 108: 7980-7984, 2011.
Beigneux, A.P., Davies, S., Tat, S., Chen, J., Gin, P., Voss, C.V., Weinstein, M.M., Bensadoun, A., Pullinger, C.R., Fong, L.G., Young, S.G. Assessing the role of the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) three-finger domain in binding lipoprotein lipase. J.Biol.Chem. 286:19735-19743,2011.
Rios, J.J., Shastry, S., Jasso, J., Hauser, N.,Garg, A., Bensadoun, A., Cohen, J.C., Hobbs, H.H. Deletion of GPIHBP1 causing severe chylomicronemia. J. Inherit.Metab. Dis. 35:531-540, 2011. PMID:22008945.
Hosseini, M., Ehrhardt, N., Weissglas-Volkov, D., Lai, C.M., Mao, H.Z., Liao, J.L., Nikkola, E., Bensadoun, A., Taskinen, M.R., Doolittle, M.H., Pajukanta, P., Peterfy, M. Transgenic expression and genetic variation of Lmf1 affect LPL activity in Mice and humans. Arterioscler.Thromb.Vasc.Biol. 32:1204-1210, 2012. PMID: 22345169.
Bensadoun, A., Nesheim, M.C., Ross, A.C. Biography of Donald Berthold Zilversmit. J.Nutr.142:211-212, 2012.
Nyren, R., Chang, C.L., Lindstrom, P., Barmina, A., Vorrsjo, E., Ali, Y., Juntti-Berggren, L., Bensadoun, A., Young, S.G., Olivecrona, T., Olivecrona, G. Localization of lipoprotein lipase and GPIHBP1 in mouse pancreas: Effects of diet and leptin deficiency. BMC Physiol. Epub ahead of print; PMID: 23186339, 2012.
Adeyo, O., Goulbourne, C.N., Bensadoun, A., Beigneux, A.P., Fong, L.G., Young, S.G. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein1 and the intravascular processing of triglyceride-rich lipoproteins. J.Intern. Med. 272:528-540. 2012. PMID:23020258.
Gin, P., Goulbourne, C.N., Adeyo, O., Beigneux, A.P., Davies, B.S., Tat, S., Voss, C.V., Bensadoun, A., Fong, L.G., Young, S.G. Chylomicronemia mutations yield new insights into interactions between lipoprotein lipase and GPIHBP1. Hum. Mol. Genet. 21: 2961-2972. 2012. PMID: 22493000
Davies, B.S., Goulbourne, C.N., Barnes, R.H. 2nd, Turlo, K.A., Gin, P., Vaughan, S., Vaux, D.J., Bensadoun, A., Beigneux, A.P., Fong, L.G., Young, S.G. Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells. J.Lipid Res. 53:2690-2697. 2012. PMID:23008484.
Nyren, R., Chang, C.L.,Lindstrom, P., Barmina, A., Vorrsjo, E., Ali, Y., Juntti-Berggren, L., Bensadoun, A., Young S.G., Olivecrona, T., Olivecrona, G. Localization of lipoprotein lipase and GPIHBP1 in mouse pancreas: effects of diet and leptin deficiency. Physiol. 12:14. 2012. PMID: 23186339.
Robciuc, M.R., Maranghi, M., Lahikainen, A., Rader, D., Bensadoun, A., Oorni, K., Metso, J., Minicocci, I., Ciociola, E., Ceci, F., Montali, M., Ehnholm, C., Jauhianen, M. Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decrease serum free fatty acids. Arterioscler Thromb vasc Biol. 33:1706-1713. PMID:23661675.
Dr Bensadoun is engaged mainly in research. He has currently an appointment as a Graduate School Professor. He has membership in following graduate fields: Nutrition; Biochemistry, Molecular and Cell Biology; Molecular and integrative Physiology.
1951, France Baccalaureate, Mathematics, Bordeaux University
1956, France Eng. of ENSAT, engineering, Toulouse University
1956, France Lic. Sc. , biology, Toulouse University
1960, Ph.D., nutrition, Cornell University