Faculty and Staff
Nutritional and Metabolic Doctoral Training Faculty
Ira A. Tabas, M.D., Ph.D.
Professor of Medicine and Anatomy and Cell Biology
B.S. 1975, Tufts University
M.D. 1981, Washington University (St. Louis)
Ph.D. 1981, Washington University (St. Louis)
Dr. Tabas' current research focuses on the cellular and molecular biology of macrophages. The laboratory utilizes cell-culture models and induced mutant mice to explore areas of macrophage cellular and molecular biology that are pertinent to the development of atherosclerosis. The laboratory studies basic cellular processes involved in the uptake, intracellular trafficking, metabolism, and cell biological effects of cholesterol. A major focus of the laboratory is the molecular and cellular consequences resulting from the accumulation of unesterified, or "free", cholesterol (FC) by macrophages. A relatively early phase of FC loading involves the adaptive induction of phosphatidylcholine biosynthesis. Eventually this adaptive response fails, and the cells undergo apoptotis. In this context, the laboratory has a major project exploring cell death pathways in cholesterol-loaded macrophages. Cholesterol loading of the endoplasmic reticulum induces a classic "ER stress" pathway known as the unfolded protein response (UPR). The Tabas lab is exploring the mechanism by which FC loading of the ER membrane induces the UPR and are using induced mutant mice to study the effect of the UPR on atherosclerosis in vivo. Macrophage cholesterol loading triggers another cell signaling pathway that leads to the accelerated degradation of an important cell-surface molecule-ABCA1-involved in cholesterol efflux from cells. Current studies are directed at elucidating the protein degradation pathway involved in this event and how this pathway is induced by cholesterol loading. Other projects in the laboratory study mechanisms of cholesterol uptake and trafficking by macrophages. Sphingomyelinases modify cholesterol-carrying lipoproteins in such a way to promote internalization and effect vescular trafficking in macrophages. Current work using confocal and multiphoton fluorescence microscopy is directed at further characterizing lipid and protein trafficking in mutant macrophages defective SMase.
Recent Publications - Pubmed
Tabas I. Apoptosis and plaque destabilization in atherosclerosis: the role of macrophage apoptosis induced by cholesterol. Cell Death Differ 11 Suppl 1:S12-6, 2004.
Leventhal, A.R., Leslie, C.C., Tabas, I. Suppression of Macrophage Eicosanoid Synthesis by Atherogenic Lipoproteins is Profoundly Affected by Cholesterol-Fatty Acyl Esterification and the Niemann-Pick C Pathway of Lipid Trafficking. J Biol Chem 279:8084-8092, 2004.
Feng, B., Zhang, D., Kuriakose, G., Kockx, M., Tabas, I. Niemann-Pick C heterozygosity confers marked resistance to lesional necrosis and macrophage apoptosis in atherosclerotic lesions of apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 100:10423-10428, 2003.