Faculty & Staff
Doctoral Training and Teaching Faculty
Alan R. Tall, M.D.
Tilden Weger Bieler Professor of Medicine
M.B.B.S. 1970, University of Sydney
Dr. Alan Tall, Professor of Medicine, heads a research program in molecular medicine and atherogenesis. Dr. Tall's research program covers three major areas: 1) ABC Transporters and Cellular Lipid Efflux. These studies encompass work on the transcriptional control mechanisms regulating expression of ABCA1, the mutant molecule in Tangier Disease. Also, studies are investigating post-transcriptional control mechanisms involving PEST-sequence regulated calpain proteolysis. The Tall laboratory has recently discovered potential functions for novel transporters: ABCA7 mediates phospholipid efflux to lipid-poor apolipoproteins but not HDL, while ABCG1 and ABCG4 are half-transporters that mediate cholesterol efflux to HDL but not to lipid-poor apolipoproteins. These novel transporters may be responsible for the protective effect of HDL and are being further evaluated in knock-out mice; 2) Mechanisms of Atherogenesis in Insulin-Resistant States. These studies have established that macrophage insulin resistance causes post-transcriptional up-regulation of CD36, representing a novel mechanism of atherogenesis in insulin-resistant states such as metabolic syndrome. Future studies are addressing the molecular players connecting insulin resistance with altered trafficking of CD36 that leads to its up-regulation; 3) Discovery of New Genes affecting Atherogenesis using Mouse Genetics. These studies have used LDL receptor KO mice in the C57Bl6 strain crossed with another inbred strain (Molf). This revealed a major locus of chromosome 4 affecting atherogenesis. By analysis of congenic and sub-congenic strains, a new gene has been discovered that profoundly affects the amount and morphology of early atherogenesis: ADAMTSL-I (a disintegrin and metalloprotease thrombospondin-like 1). This gene might regulate the activity of ADAM proteases within the arterial wall thereby affecting macrophage viability and atherogenesis. Future studies are planned to elucidate the functions of ADAMTSL-1, especially as they relate to atherogenesis, and to assess possible human genetic variation in this gene and its relationship to atherosclerotic risk.
Recent Publications - Pubmed
Liang CP, Han S, Okamoto H, Carnemolla R, Tabas I, Accili D, Tall AR. Increased CD36 protein as a response to defective insulin signaling in macrophages. J Clin Invest 113:764-73, 2004.
Wang N, Lan D, Chen W, Matsuura F, Tall AR. ATP-Binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. PNAS 101:9774-9779, 2004.
Wang N, Chen W, Linsel-Nitschke P, Martinez L, Agerholm-Larsen B, Silver DL, Tall AR. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest 111:99-107, 2003.