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	Allan Tall, M.D. Tilden Weger Bieler Professor of Medicine Division of Molecular Medicine College of Physicans & Surgeons of Columbia University 630 West 168th St., P & S 8-401, New York, N. Y., 10032 Email: art1@columbia.edu Tel: (212) 305-9418 Fax: (212) 305-5052 Contact Person: Tania Guzman (212) 305-4899
CURRENT RESEARCH 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. SELECTED PUBLICATIONS Linsel-Nitschke, P., and Tall, A.R. 2005. HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov. 4, 193-205. Liang, C.P., Han, S., Okamoto, H., Carnemolla, R., Tabas, I., Accili, D., and Tall, A.R. 2004. Increased CD36 protein as a response to defective insulin signaling in macrophages. J Clin Invest. 113, 764-73. Wang, N., Lan D., Chen, W., Matsuura, F., and Tall, A.R. 2004. ATP-Binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. PNAS 101, 9774-9779. Wang, N., Chen, W., Linsel-Nitschke, P., Martinez, L., Agerholm-Larsen, B., Silver, D.L., and Tall, A.R. 2003. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest. 111, 99-107. Barter, P.J., Brewer, H.B. Jr, Chapman, M.J., Hennekens, C.H., Rader, D.J., Tall, A.R. 2003. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. ATVB 23, 160-7. Review. Wang, N., Lan, D., Gerbod-Giannone, M., Linsel-Nitschke, P., Jehle, A.W., Chen, W., Martinez, L.O., and Tall, A.R. 2003. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipids but not cholesterol efflux. J Biol. Chem. 278, 42906-12. Costet, P., Lalanne, F., Gerbod-Giannone, M.C., Molina, J.R., Fu, X., Lund, E.G., Gudas, L.J., and Tall, A.R. 2003. Retinoic acid recptor-mediated induction of ABAC1 in macrophages. Mol. Cell Biol. 23, 7756-66. Jiang, X.C., Qin,, S., Qiao, C., Kawano, K., Lin, M., Xiao, X., and Tall, A.R. 2001. Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat. Med. 7, 847-52.
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