TALL, ALLAN, M.D. Tilden Weger Bieler Professor of Medicine The laboratory is carrying out research on the molecular mechanisms responsible for human diseases such as atherosclerosis and Alzheimer's Disease. Email:art1@cumc.columbia.edu

Current Research

The Tall laboratory is conducting research on the pathogenesis of metabolic diseases including atherosclerosis, obesity and fatty liver. A major focus has been on the effects of deleting ATP binding cassette transporters ABCA1 and ABCG1 in specific cell types. These transporters promote efflux of cholesterol from cells to plasma HDL particles. Consequently, deletion of transporters in hematopoietic and immune cells leads to cholesterol accumulation and disordered cellular functions including excessive proliferation and inflammatory responses. Another major area of interest is to use information derived from human genome wide association studies to identify novel genes that are involved in modulating the impact of metabolic diseases. This has led to the discovery that mutations in genes that cause hematological malignancies also promote atherosclerosis in mouse models and in humans. As people age they commonly acquire such mutations: this increases their risk of developing hematological malignancies but also unexpectedly diabetes and atherosclerosis. We are working to try to understand the underlying cellular and molecular mechanisms which include excessive proliferation of hematopoietic stem cells, increased myelopoiesis and platelet production, platelet activation and macrophage inflammation. A further goal is to use these mechanistic discoveries as a guide to new therapeutic approaches to treating human metabolic diseases.

Selected Publications

Westerterp M, Gautier EL, Ganda A, Molusky MM, Wang W, Fotakis P, Wang N, Randolph GJ, D'Agati VD, Yvan-Charvet L, Tall AR. Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity. Cell Metab. 2017 Jun 6;25(6):1294-1304.

Tall AR, Levine RL. Cardiovascular disease: Commonality with cancer. Nature. 2017 Mar 543(7643):45-47.

Wang W, Tang Y, Wang Y, Tascau L, Balcerek J, Tong W, Levine RL, Welch C, Tall AR, Wang N. LNK/SH2B3 Loss of Function Promotes Atherosclerosis and Thrombosis. Circ Res. 2016 Sep 2;119(6):e91-e103.

Hsieh J, Koseki M, Molusky MM, Yakushiji E, Ichi I, Westerterp M, Iqbal J, Chan RB, Abramowicz S, Tascau L, Takiguchi S, Yamashita S, Welch CL, Di Paolo G, Hussain MM, Lefkowitch JH, Rader DJ, Tall AR. TTC39B deficiency stabilizes LXR reducing both atherosclerosis and steatohepatitis. Nature. 2016 Jul 14;535(7611):303-7.

Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015 Feb;15(2):104-16.

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.