Mary G. Sorci-Thomas
Associate Professor of Comparative Medicine and Associate in Biochemistry 

B.S., 1979 (Biochemistry/Chemistry) Louisiana State University
Ph.D., 1984 (Biochemistry) Bowman Gray School of Medicine of Wake Forest University
Postdoctorate, 1984-1987 (Molecular Biology) State University of New York at Stony Brook

Current Projects: Apo A-I Structure: Function and The Development of Arteriosclerosis. Quality Control of Apo A-I Secretion. Crystalliztion of Phospholipid Apo A-I Complexes for X-ray Diffraction Studies The incidence of premature coronary atherosclerosis in the human population is highly correlated to decreased concentrations of plasma high density lipoprotein (HDL) and its major apoprotein, apo A-I (apo A-I). Transgenic and knockout mouse studies have shown that circulating HDL apo A-I primarily plays a "protective function" in response to high levels of atherogenic lipoproteins through its ability to accept, organize and transport cholesterol out of the artery to the liver for uptake and excretion into bile. This "reverse cholesterol transport pathway" is highly dependent upon apo A-I's ability to activate the enzyme lecithin:cholesterol acyltransferase (LCAT) for cholesterol to cholesterol ester conversion in the plasma. Blockage or reduction in apo A-I's ability to carry out this function can lead to reduced reverse cholesterol transport and inefficient removal of peripheral tissue cholesterol. Data from our laboratory show that structural alterations in the conformation of plasma apo A-I can have a more profound effect on HDL apo A-I formation and maturation than merely the absence of native apo A-I alone. Our studies show that LCAT activation and thus, plasma cholesterol esterification is inhibited by the presence of a mutant form of apo A-I in plasma. The mutant apo A-I does this by inhibiting plasma cholesterol esterification even in plasma containing native or wild-type apo A-I. Thus, our studies will investigate the molecular and cellular basis for the severe disruption in HDL metabolism resulting from the hepatic expression of the mutant forms of human apo A-I. One such mutant currently under study, lacks repeat 6, a single proline punctuated 22-mer and is refer to as Delta6 apo A-I. In a newly created transgenic mouse model, designated TgDelta6 apo A-I we are conducting dietary-cholesterol feeding studies to determine if this mutant apo A-I protects against atherosclerosis in mice with hypercholesterolemia.

Recent Publications (selected):

Sorci-Thomas MG, Curtiss L, Landrum M. Single repeat deletion in apo A-I blocks cholesterol esterification and results in rapid catabolism of Delta6 and wild-type apo A-I in transgenic mice. J. Biol. Chem. 275:12156-12163 (2000).

Sorci-Thomas MG, Curtiss L, Parks JS, Thomas MJ, Kearns MW, Landrum M.:  The hydrophobic face orientation of apolipoprotein A-I amphipathic helix domain 143-164 regulates lecithin:cholesterol acyltransferase activation. J. Biol. Chem. 273:11776-82 (1998).

Colvin PL Jr, Wagner JD, Adams MR, Sorci-Thomas MG.:  Sex steroids increase cholesterol 7alpha-hydroxylase mRNA in nonhuman primates.  Metabolism 47:391-5 (1998).

Sorci-Thomas MG, Curtiss L, Parks JS, Thomas MJ, Kearns MW.:  Alteration in apolipoprotein A-I 22-mer repeat order results in a decrease in lecithin:cholesterol acyltransferase reactivity. J. Biol. Chem. 272:7278-84 (1997).

Sorci-Thomas MG, Parks JS, Kearns MW, Pate GN, Zhang C, Thomas MJ.:  High level secretion of wild-type and mutant forms of human proapoA-I using baculovirus-mediated Sf-9 cell expression. J. Lipid Res. 37:673-83 (1996).

Miller KR, Wang J, Sorci-Thomas M, Anderson RA, Parks JS.:  Glycosylation structure and enzyme activity of lecithin:cholesterol acyltransferase from human plasma, HepG2 cells, and baculoviral and Chinese hamster ovary cell expression systems.  J. Lipid Res. 37:551-61 (1996).