Education:

• Undergraduate: Louisiana State University, BS, 1979
• Postgraduate: Wake Forest University, PhD, 1984
• Fellowship: State University of New York at Stony Brook, 1984-87 

Interests:

• Teaching: Pathobiology of Atherosclerosis, Molecular Biology, Techniques in Biochemistry
• Research: Apo A-I Activation of LCAT and the Control of Plasma HDL Concentrations 

Current Research: Apo A-I Structure: Function and The Development of Arteriosclerosis. Quality Control of Apo A-I Secretion. Crystallization 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. 

Figure Legends: Transgenic and knockout mice are used in the research study of HDL apo A-I metabolism (above). Mice expressing mutant forms of human apo A-I have been generated and are helping to unravel metabolic pathways which are involved in the maturation of nascent HDL to spherical HDL (below).

Recent Publications:

Bhat S, Sorci-Thomas MG, Tuladhar R, Samuel MP, Thomas MJ. Conformational adaptation of apolipoprotein A-I to discretely sized phospholipid complexes. Biochemistry. 2007 Jul 3;46(26):7811-21.

Owen JS, Bharadwaj MS, Thomas MJ, Bhat S, Samuel MP, Sorci-Thomas MG. Ratio determination of plasma wild-type and mutant apoA-I using mass spectrometry: quantification, purification and expression of L159R apoA-I (apoA-IFin). J Lipid Res. 2007 Jan;48(1):226-34

Zabalawi M, Bharadwaj M, Horton H, Cline M, Willingham M, Thomas MJ, Sorci-Thomas MG. Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance? J Lipid Res. 2007 Jan;48(1):52-65.

Thomas MJ, Bhat S, Sorci-Thomas MG. The use of chemical cross-linking and mass spectrometry to elucidate the tertiary conformation of lipid-bound apolipoprotein A-I. Curr Opin Lipidol. 2006 Jun;17(3):214-20. Review.

Ou J, Wang J, Xu H, Ou Z, Sorci-Thomas MG, Jones DW, Signorino P, Densmore JC, Kaul S, Oldham KT, Pritchard KA Jr. Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet. Circ Res. 2005 Oct 13; 2005 Nov 25;97(11):1190-7.

Bhat S, Sorci-Thomas MG, Alexander ET, Samuel MP, Thomas MJ. Intermolecular contact between globular N-terminal fold and C-terminal domain of ApoA-I stabilizes its lipid-bound conformation: studies employing chemical cross-linking and mass spectrometry. J Biol Chem. 2005 Sep 23;280(38):33015-25.

Alexander ET, Bhat S, Thomas MJ, Weinberg RB, Cook VR, Bharadwaj MS, Sorci-Thomas M. Apolipoprotein A-I helix 6 negatively charged residues attenuate lecithin-cholesterol acyltransferase (LCAT) reactivity. Biochemistry. 2005 Apr 12;44(14):5409-19.

Bhat S, Zabalawi M, Willingham MC, Shelness GS, Thomas MJ, Sorci-Thomas MG. Quality control in the apoA-I secretory pathway: deletion of apoA-I helix 6 leads to the formation of cytosolic phospholipid inclusions. J Lipid Res. 2004 Jul;45(7):1207-20.

Zabalawi M, Bhat S, Loughlin T, Thomas MJ, Alexander E, Cline M, Bullock B, Willingham M, Sorci-Thomas MG. Induction of fatal inflammation in LDL receptor and ApoA-I double-knockout mice fed dietary fat and cholesterol. Am J Pathol. 2003 Sep;163(3):1201-13.

Schwenke DC, Rudel LL, Sorci-Thomas MG, Thomas MJ. alpha-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits. J Lipid Res. 2002 Nov;43(11):1927-38.

Li HH, Lyles DS, Pan W, Alexander E, Thomas MJ, Sorci-Thomas MG. Apo A-I structure on discs and spheres: Variable helix registry and conformational states. J Biol Chem. 2002 Oct 18;277(42):39093-101.

Sorci-Thomas MG, Thomas MJ. The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med. 2002 Apr;12(3):121-8. Review.

Reschly EJ, Sorci-Thomas MG, Davidson WS, Meredith SC, Reardon CA, Getz GS. Apolipoprotein A-I alpha -helices 7 and 8 modulate high density lipoprotein subclass distribution. J Biol Chem. 2002 Mar 22;277(12):9645-54.

Li HH, Thomas MJ, Pan W, Alexander E, Samuel M, Sorci-Thomas MG. Preparation and incorporation of probe-labeled apoA-I for fluorescence resonance energy transfer studies of rHDL. J Lipid Res. 2001 Dec;42(12):2084-91.

Thomas MJ, Chen Q, Sorci-Thomas MG, Rudel LL. Isoprostane levels in lipids extracted from atherosclerotic arteries of nonhuman primates. Free Radic Biol Med. 2001 Jun 15;30(12):1337-46.

Thomas MJ, Chen Q, Zabalawi M, Anderson R, Wilson M, Weinberg R, Sorci-Thomas MG, Rudel LL. Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids? Biochemistry. 2001 Feb 13;40(6):1719-24.

Li H, Lyles DS, Thomas MJ, Pan W, Sorci-Thomas MG. Structural determination of lipid-bound ApoA-I using fluorescence resonance energy transfer. J Biol Chem. 2000 Nov 24;275(47):37048-54.

Sorci-Thomas MG, Thomas M, Curtiss L, Landrum M. Single repeat deletion in ApoA-I blocks cholesterol esterification and results in rapid catabolism of delta6 and wild-type ApoA-I in transgenic mice. J Biol Chem. 2000 Apr 21;275(16):12156-63.

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. 1998 May 8;273(19):11776-82.

Colvin PL Jr, Wagner JD, Adams MR, Sorci-Thomas MG. Sex steroids increase cholesterol 7alpha-hydroxylase mRNA in nonhuman primates. Metabolism. 1998 Apr;47(4):391-5.

Contact Us

Department of Pathology
Section on Lipid Sciences
Wake Forest University School of Medicine
Medical Center Boulevard
Winston-Salem, NC 27157

Tel: (336) 716-2821
Fax: (336) 716-6279