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Stephen G. Young, M.D.
Professor of Medicine
Director, Cellular and Molecular Cardiology Unit
Office:  4770 MRL
Phone:  (310) 825-4934, (310) 825-4997
Email:  sgyoung@mednet.ucla.edu 
 

Curriculum Vitae

Research Interest

During the past few years, we have worked on two general areas, the pathogenesis of hypertriglyceridemia and diseases of the nuclear lamina.

Our group discovered a GPI-anchored endothelial cell protein, GPIHBP1, that is critically important for the lipoprotein lipase–mediated processing of triglyceride-rich lipoproteins. Mutations in GPIHPB1 in mice and humans cause severe hypertriglyceridemia. Over the next few years, we intend to focus on the cell biology of GPIHPB1 and define the precise role of GPIHPB1 regulating plasma triglyceride levels.

We have also sought to define the in vivo importance of lipid modifications of proteins. Much of this work has been focused on the nuclear lamins, which are posttranslationally modified by a cholesterol biosynthetic intermediate. The nuclear lamins are building blocks for the nuclear lamina—a structural scaffolding for the cell nucleus. Defects in the posttranslational processing of one of the nuclear lamins (lamin A) is associated with a devastating pediatric genetic disease, progeria. We proposed that abnormal posttranslational processing of the nuclear lamins might contribute to the pathogenesis of disease, and we further hypothesized that drugs that interfere with the posttranslational processing pathway might improve disease phenotypes. At least in the mouse, our hypothesis proved to be correct.

Over the next few years, our laboratory will work to define the in vivo importance of the B-type lamins, lamin B1 and lamin B2.

Our laboratory works on specific molecules, and we make use of diverse techniques in molecular and cellular biology. We are also experts in the creation of genetically modified mouse models, and when appropriate, we make use of mouse models to address our research questions.

Representative Publications

Weinstein MM, Yin L, Beigneux AP, Davies BS, Gin P, Estrada K, Melford K, Bishop JR, Esko JD, Dallinga-Thie GM, Fong LG, Bensadoun A, Young SG. (2008) Abnormal patterns of lipoprotein lipase release into the plasma in GPIHPB1-deficient mice, J. Biol. Chem., 12, 34511–34518.

Beigneux AP, Davies BS, Gin P, Weinstein MM, Farber E, Qiao X, Peale F, Bunting S, Walzem RL, Wong JS, Blaner WS, Ding ZM, Melford K, Wongsiriroj N, Shu X, de Sauvage F, Ryan RO, Fong LG, Bensadoun A, Young SG. (2007) Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metabolism, 5, 279–291.

Coffinier C, Hudon SE, Farber EA, Chang SY, Hrycyna CA, Young SG, Fong LG. (2007) HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc. Natl. Acad. Sci. USA, 104, 13432-13437.

Yang SH, Andres DA, Spielmann HP, Young SG, and Fong LG., Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J. Clin. Invest., 2008, 118, 3291-3300.

Gin P, Yin L, Davies BSJ, Weinstein MM, Ryan RO, Bensadoun A, Fong LG, Young SG, and Beigneux AP, The acidic domain of GPIHBP1 is important for the binding of lipoprotein lipase and chylomicrons, J Biol. Chem. 2008, 283, 29554-29562.

Brandon S. J. Davies, Anne P. Beigneux, Richard H. Barnes II, Yiping Tu, Peter Gin, Michael M. Weinstein, Chika Nobumori, Rakel Nyrén, Ira Goldberg, Gunilla Olivecrona, André Bensadoun, Stephen G. Young, Lipase into Capillaries. Cell Metabolism 2010; In Press:

Coffinier C, Chang SY, Nobumori C, Farber EA, Toth J, Fong LG, and Young SG. Abnormal Development of the Cerebral Cortex and Cerebellum in the Setting of Lamin B2 Defiency.. Proc.Natl.Acad.Sci 2010; (107): 5076-5081.

Lee R, Chang SY, Trinh H, White AC, Bergo MO, Fong LG, Lowry WE, and Young SG. Genetic Analysis of the Importance of the Protein Prenyltransferases in Skin Keratinocytes. Human Molecular Gen. 2009; (19): 1603-1617.

Coffinier C, Jung HJ, Li Z, Nobumori C, Yun UJ, Farber EA, Davies BS, Weinstein MM, Yang SH, Lammerding J, Farahani JN, Bentolila LA, Fong LG, Young SG. Direct Synthesis of Lamin A, Bypassing Prelamin A Processing, Causes Misshapen Nuclei in Fibroblasts but No Detectable Pathology in Mice. J Biol Chem 2010; (May 3):

Davies BS, Barnes RH 2nd, Tu Y, Ren S, Andres DA, Spielmann HP, Lammerding J, Wang Y, Young SG, Fong LG. An Accumulation of Non-Farnesylated Prelamin A Causes Cardiomyopathy but Not Progeria.. Hum Mol Genet. 2010; (May4):

Beigneux AP, Gin P, Davies BS, Weinstein MM, Bensadoun A, Fong LG, Young SG. Highly Conserved Cysteines within the Ly6 domain of GPIHBP1 are Crucial for the Binding of Lipoprotein Lipase: J. Biol. Chem. 2009; (284): 30240 - 30247.

Weinstein MM, Yin L, Tu Y, Wang X, Wu X, Castellani LW, Walzem RL, Lusis AL, Fong LG, Beigneux AP, Young SG. Chylomicronemia Elicits Atherosclerosis in Mice. Arterioscler Thromb Vasc Biol. 2010; (30): 20-23.

Beigneux AP, Franssen R, Bensadoun A, Gin P, Melford K, Peter J, Walzem RL, Weinstein MM, Davies BS, Kuivenhoven JA, Kastelein JJ, Fong LG, Dallinga-Thie GM, Young SG. Chylomicronemia with a Mutant GPIHBP1 (Q115P) that Cannot Bind Lipoprotein Lipase. . Arterioscler Thromb Vasc Biol. 2009; (29): 956-962.

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