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      Assistant Professor of Molecular Medicine (in Medicine)

Molecular genetics of lipid metabolism in both humans and induced mutant mouse models:

Elevated plasma levels of low density lipoprotein (LDL) and apolipoprotein B (apo B) are associated with a higher risk for atherosclerosis and coronary heart disease, a leading cause of mortality in the industrialized world. Apo B is the mandatory constituent of LDL particles. In addition to its role in the lipoprotein metabolism, our previous research has revealed novel functional role for apo B such as male infertility and fetal development. More recently, we have identified two quantitative trait loci regulating plasma apo B levels using transgenic mouse models. My laboratory is in the process of fine mapping and positional cloning of these two loci. Results from these studies will facilitate the identification of human orthologus genes regulating plasma apo B levels. These loci are novel candidates for human disorders with altered plasma apo B levels such as non-apo B linked hypobetalipoproteinemia and familial combined hyperlipidemia. The identification of these loci may also reveal new pathways involved in the regulation of apo B secretion, potentially providing novel sites for pharmacological therapy. My laboratory is also interested in determining the genetic basis of diet responsiveness and nutrient-gene interactions. We have recently shown that the responsiveness of plasma apo B levels to dietary omega-3 fatty acids is genetically regulated in congenic human apo B mouse strains. We are currently conducting molecular and cellular studies to elucidate the molecular mechanisms underlying the strain differences in the responsiveness to fish oil feeding. Results from these studies will improve our understanding into the beneficial and potentially unfavorable effects of dietary omega-3 fatty acids. The eventual identification and cloning the gene(s) which regulate responsiveness to omega-3 fatty acids will also allow for the detection of genetic variants in the general population. These results will yield informative results which will provide nutritionists to formulate appropriate guidelines for the general public for consuming food products enriched in n-3 fatty acids.

      Division of Preventive Medicine
      Columbia University, College of Physicians & Surgeons
      PH 10-305
      630 West 168th Street
      New York, NY 10032
      Ph. 212-305-9594
      Fax: 212-305-3213
      Email: lh99@columbia.edu

1979B.S. - Biology, Fu-Jen University, Taipei, Taiwan
1984Ph.D. - Biological Sciences/Genetics and Development, University of Delaware, Newark, DE
1984-1987Postdoctoral Associate - Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY
1987Research Associate, Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY
1985-1995Assistant Professor, Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY
1995Assistant Professor, Department of Medicine, Division of Preventive Medicine & Nutrition, Columbia University, College of Physicians & Surgeons, New York, NY
1977-1979Academic Scholarship, Fu-Jen Catholic University
1980-1981Academic Scholarship, University of Delaware
1981-1983UNIDEL Research Fellowship, University of Delaware
1988-1991Sinsheimer Foundation Award
1989-1994Hirschl/Weill-Caulier Award
1989-1992Investigatorship Award, American Heart Association, New York City Affiliate
1990-1991Ella Fitzgerald Fellowship for Research, American Heart Association, New York City Affiliate
1993-1998Established Scientist Award, American Heart Association, New York City Affiliate
1981American Association for the Advancement of Science
1987New York Academy of Sciences
1987American Heart Association
1997Fellow, Council on Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association

Heinemann, T., Metzger, S., Fisher, E.A., Breslow, J.L., Huang, L-S, Alternative polyadenylation is a major cause of apolipoprotein B-48 formation in rat hepatoma cell lines transfected with human apo B-100 minigenes., Journal of Lipid Research, 35:2200-2211, 1994

Zhou, M., Wu, X., Huang, L-S, Ginsberg, H.N., Apolipoprotein B-100, an inefficiently translocated secretory protein, is bound to a cytosolic chaperone, heat shock protein., J Biol Chem, 270:25220-25224, 1995

Huang, L-S, Voyiaziakis E., Markenson, D.F., Sokol, K.A., Hayek, T. ,Breslow, J., Apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesteryl ester and apo A-I transport in heterozygotes., J Clin Invest., 96:2152-2161, 1995

Wu, X., Zhou, M., Huang, L-S, Wetterau, J., Ginsberg, H.N., Demonstration of a physical interaction between microsomal triglycerides transfer protein and apolipoprotein and apolipoprotein B during the assembly of apo B-containing lipoproteins., J Biol Chem, 271:10277-10281, 1996

Huang, L-S, Voyiaziakis, E., Chen, H.L., Rubin, E.M., Gordon, J.W., A novel functional role for apolipoprotein B in male infertility in heterozygous apo B knockout mice., Proc Natl Acad Sci USA, 93:10903-10907, 1996

Voyiaziakis, E., Goldberg, I.J., Plump, A.S., Rubin, E.M., Breslow, J.L., Huang, L-S, Apo A-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in human apo B transgenic mice., J. Lipid Res, 39:313-329, 1998

Liang, J-S, Wu, X., Jiang, H., Zhou, M., Yang, H., Angkeow, P., Huang, L-S, Sturley, S.L., Ginsberg, H.N., Translocation efficiency, susceptibility to proteasomal degradation, and lipid responsiveness of apolipoprotein B are determined by the presence of B sheet domains., J. Biol. Chem., 273:35216-35221, 1998

Voyiaziakis, E., Ko, C., O'Rourke, S.M., Huang, L-S, Genetic control of hepatic apo B-100 secretion in human apo B transgenic mouse strains., Journal of Lipid Research, 40:2004-2012, 1999

Kako, Y., Huang, L-S, Young, J., Katopodis, T., Ramakrishnan, S., Goldberg, I.J., Streptozotocin-induced diabetes in human apo B transgenic mice: effects on lipoproteins and atherosclerosis., J .Lipid Res., 40:2185-2194, 1999

Huang, L-S, Siri, P., Candela, N., Ebara, T., Eusufsai, S., Ginsberg, H.N., Hypertriglyceridemia and increased VLDL secretion in human apolipoprotein B transgenic mice with brown adipose tissue deficiency: A mouse model for post-translational regulation of apolipoprotein B secretion, and for the dyslipidemia associated with insulin resistance., Submitted

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Updated: April 12, 2000