The laboratory is carrying out research on the molecular mechanisms responsible for human diseases. The approach is to use molecular, genomic and cellular approaches to investigate basic aspects of the pathogenesis of atherosclerosis and Alzheimer's Disease. In the area of atherosclerosis, a major focus is on molecular mechanisms of cellular cholesterol efflux, mediated by the interaction of apoA-I with ABCA1. We are carrying out studies on the transcriptional regulation of ABCA1 gene expression, and regulation of the degradation of ABCA1 protein. This has led to the elucidation of a class of transcription factors (LXRs) that co-ordinately regulate cellular cholesterol efflux and reverse cholesterol transport. Recently, we have discovered a link with Alzheimer's Disease, as cellular cholesterol efflux also regulates the formation of amyloid ß-peptide. Another important area of research relates to the mechanisms of increased atherosclerosis in diabetes. These studies are focusing on insulin resistance at the level of the macrophage, resulting in enhanced uptake of oxidized LDL. This also involves mapping of atherosclerosis and insulin resistance genes in mouse models of atherosclerosis and diabetes.
Division of Molecular Medicine
College of Physicans & Surgeons of Columbia University
630 West 168th St., P & S 8-401, New York, N. Y., 10032
Contact Person: Tania Guzman
|1997 - Present, Director, Specialized Center of Research (SCOR) in Molecular Medicine and Atherosclerosis, Columbia University|
|1996 - Present, Tilden Weger Bieler Professor of Medicine, Columbia University|
|1990 - 1996, Director, Specialized Center of Research (SCOR) in Atherosclerosis, Columbia University|
|1989 - Present, Professor of Medicine, Columbia University|
|1989 - Present, Attending Physician, Presbyterian Hospital|
|1982 - 1989, Associate Professor of Medicine, Columbia University|
|1978 - 1981, Assistant Professor of Medicine, Columbia University, College of Physicians & Surgeons, New York|
|1977, Assistant Professor of Medicine, Boston University, Boston, MA|
|1976 - 1977, Assistant Visiting Physician, Boston City Hospital, Boston, MA|
|1975 - 1976, Chief Resident, Medical Service, Boston City Hospital, Boston, MA|
|1974 - 1975, Gastroenterology Fellow, University Hospital, Boston, MA|
|1973 - 1974, Senior Resident, Medical Service, Boston City Hospital, Boston, MA|
|1972, Resident, Royal Prince Alfred Hospital, Sydney, Australia|
|1971, Intern, Royal Prince Alfred Hospital, Sydney, Australia|
|1970 M.B., B.S. (honors) University of Sydney, Sydney, Australia|
|1995 - 2000, Board of Scientific Counselors, NHLBI|
|1994 -1999, Chair Page Award Committee, AHA; Chairman, (1996 - 1997)|
|1992 -present, Scientific Advisory Board to Gladstone Research Foundation, UCSF|
|1999 - 2000, Research Committee, American Heart Association|
|1989, Association of American Physicians|
|1987 - 1989, Executive Committee, Arteriosclerosis Council, American Heart Association|
|1985 - 1986, Program Committee, American Heart Association|
|1982, American Society of Clinical Investigation|
|1996 - 1998, Tenure Review Advisory Committee, Columbia; University|
|1993 - 1995, Committee on Appointments and Promotions, Columbia University, Chairman, 1995.|
Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR; Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency: Nature Medicine 2001 Jul;7(7):847-52.
Wang N, Silver DL, Thiele C, Tall AR; ATP-binding cassette treansporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein: J Biol Chem. 2001 Jun 29;276(26):23742-7.
Silver DL, Wang N, Xiao X, Tall AR; High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion: J Biol Chem. 2001 Jul 6;276(27):25287-93.
Tall AR, Wang N. Tangier Disease as a test of the Reverse Cholesterol transport hypothesis Commentary. J. Clin. Invest. 2000(10):1205-1207.
Rubin EM, Tall AR. Perspectives for vascular genomics. Nature. 2000 Sep 14;407(6801):265-9
Costet P, Luo Y, Wang N, Tall AR Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem. 2000 Sep 8;275(36):28240-5.
Luo Y, Tall AR. Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J Clin Invest. 2000 Feb;105(4):513-20.
Inazu, A., Brown, M.L., Hesler, C.B., Agellon, L.B., Koizumi, J., Takata, K., Maruhama, Y., Mabuchi, H., and Tall, A.R.: Increased high density lipoprotein caused by a common cholesteryl ester transfer protein gene mutation. N. Engl. J. Med., 323:1234-1238, 1990.
Welch, CL, Bretschger S, Latib N, Bezouevski M, Guo Y, Pleskac N, Liang CP, Barlow C, Dansky H, Breslow JL, Tall AR; Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model: Proc Natl Acad Sci U S A, Jul 3 1998(14):7946-51.
Brown, M.L., Inazu, A., Hesler, C.B., Agellon, L.B., Mann, C., Whitlock, M.E., Marcel, Y.L., Milne, R.W., Koizumi, J., Mabuchi, H., Takeda, R., and Tall, A.R.: Molecular basis of lipid transfer protein deficiency in a family with increased high density lipoproteins. Nature, 342:448-451, 1989.