F A C U L T Y P R O F I L E
TALL, ALLAN, M.D.
The laboratory is carrying out research on the molecular mechanisms responsible for human diseases such as atherosclerosis and Alzheimer's Disease.
Office: Physicians & Surgeons | 8th floor | Room 401
The laboratory is conducting research on the molecular mechanisms underlying atherosclerosis, thrombosis and autoimmunity. A longstanding interest has been on the role of HDL and cholesterol efflux pathways in suppressing atherogenesis. Currently, we are using mice with conditional knockouts of cholesterol efflux transporters to explore the role of cholesterol efflux pathways in macrophages, dendritic cells and hematopoietic stem cells, and effects on the production of inflammatory cells, antigen presentation by dendritic cells and platelet production. In another project, we are exploring the in vivo and cellular functions of novel HDL genes identified in human genome wide association studies. One factor TTC39B appears to be a scaffolding protein that is involved in the post-transcriptional stabilization of the transcription factor LXR by regulation of its proteasomal degradation. Since LXR acts as a master regulator of cellular cholesterol uptake and efflux pathways, inhibition of TTC39B could be a strategy for decreasing atherosclerosis. The laboratory is also investigating the mechanisms linking diabetes and atherosclerosis, again focusing on genes identified in human GWAS for diabetes or lipoprotein changes.
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.