Mary Sorci-Thomas, PhD

Mary Sorci-Thomas, PhDProfessor of Medicine
Division of Endocrinology, Department of Medicine

Health Research Center, H4210
(414) 955-5728 | (414) 955-6570 (fax)

msthomas@mcw.edu

Faculty Collaboration Database - Mary Sorci Thomas PhD

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  Research Interest

My research group is interested in elucidating the protective role that high density lipoproteins (HDL) play in preventing coronary heart disease in humans. Studies have shown that plasma HDL and its main protein constituent, apoA-I, imparts a protective function against the damaging effects of atherogenic lipoproteins, such as circulating LDL, on the artery wall and the development of atherosclerosis. ApoA-I possesses a unique ability to accept, organize and transport cholesterol from the periphery to the liver for excretion. If the function of apo A-I is reduced or blocked, then inflammatory responses are initiated which then lead to heart disease and stroke.

One ongoing project in my lab has been to investigate the role of HDL apo A-I concentrations in reducing the development of autoimmunity and atherosclerosis. Since the immune system is a complex system with multiple layers of regulation to prevent reactions against self-antigens, or autoimmune disorders, it is possible that accumulation of cholesterol may alter cellular function to a point at which peripheral self-tolerance is lost.  We have been particularly interested in the role of T cell activation and effector T cell response in autoimmunity and atherosclerosis. HDL apo A-I appears to be linked to autoimmunity, since individuals with decreased levels of HDL apo A-I are more likely to develop autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. In hypercholesterolemic mice lacking HDL apo A-I an autoimmune phenotype develops in response to the consumption of a cholesterol containing diet.  These mice show heightened lymph node immune cell activation, proliferation and severe skin lesions. Interestingly these mice also show an increased population of T regulatory cells which are designed to modulate T cell activation. These results suggest that the Treg response under low HDL apo A-I conditions may lead to defective regulation of tolerance in these mice.

Another important area of research currently being studied in my lab concerns the formation of nascent HDL (nHDL) apo A-I particles. Since the concentration of HDL apo A-I varies greatly within the human population we are interested in determining the mechanism explaining how nascent HDL particles are formed.  One approach we are using is to investigate the composition of the particles formed following the interaction between apo A-I and the ATP binding cassette transporter A1 (ABCA1) which transports cholesterol out of the cell onto the outer leaflet of the cellular membrane. To our surprise we have found that the lipid compositions of nHDL as determined by LC-MS/MS contain a large amount of sphingomyelin and suggest that lipid rafts may significantly contribute to the ABCA1 mediated formation of newly formed nascent HDL apo A-I particles. In addition, we are also using mass spectrometry techniques to determine the conformation of apo A-I on this small lipid containing particles. These molecular studies are useful in solving the structure of lipid bound proteins which are responsible for activating important plasma enzymes such as the lecithin:cholesterol acyltransferase (LCAT).

  Publications

Milasan, A, Jean, G, Dallaire, F, Tardif, JC, Merhi, Y, Sorci-Thomas, M, Martel, C. (2017) J. Am Heart Assoc. Sep22;6(9) In Press.

Williams JW, Elvington AF, Ivanov S, Kessler S, Luehmann H, Baba O, Saunders BT, Kim KW, Johnson MW, Craft CS, Choi JH, Sorci-Thomas MG, Zinselmeyer BH, Brestoff JR, Liu Y, Randolph GJ. 2017. Circ Res. 6:662-676

Sorci-Thomas, MG and Thomas, MJ. 2017. Anti-inflammatory liaisons: T regulatory cells and HDL. J. Lipid Res. 58;1491.

Sorci-Thomas, MG and Thomas, MJ. 2017. AIBP, NAXE, and Angiogenesis: What’s in a Name? Circ Res. 120; 1690.

Hoekstra M, Sorci-Thomas M.   Rediscovering scavenger receptor type BI: surprising new roles for the HDL receptor.   Curr Opin Lipidol.   2017 Mar 15.

Lee MH, Appleton KM, El-Shewy HM, Sorci-Thomas MG, Thomas MJ, Lopes-Virella MF, Luttrell LM, Hammad SM, Klein RL.   S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.   J Lipid Res.   2017 Feb;58(2):325-338.

Kaul S, Xu H, Zabalawi M, Maruko E, Fulp BE, Bluemn T, Brzoza-Lewis KL, Gerelus M, Weerasekera R, Kallinger R, James R, Zhang YS, Thomas MJ, Sorci-Thomas MG.   Lipid-Free Apolipoprotein A-I Reduces Progression of Atherosclerosis by Mobilizing Microdomain Cholesterol and Attenuating the Number of CD131 Expressing Cells: Monitoring Cholesterol Homeostasis Using the Cellular Ester to Total Cholesterol Ratio.   J Am Heart Assoc.   2016 Nov 07;5(11).

Pollard RD, Fulp B, Sorci-Thomas MG, Thomas MJ.   High-Density Lipoprotein Biogenesis: Defining the Domains Involved in Human Apolipoprotein A-I Lipidation.   Biochemistry.   2016 Sep 06;55(35):4971-81.

Cheng HY, Gaddis DE, Wu R, McSkimming C, Haynes LD, Taylor AM, McNamara CA, Sorci-Thomas M, Hedrick CC. Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis.   J Clin Invest.   2016 Sep 01;126(9):3236-46.

Sorci-Thomas MG, Thomas MJ.   Microdomains, Inflammation, and Atherosclerosis.   Circ Res.   2016 Feb 19;118(4):679-91.

Navratil, AR, Vozenilek, AE, Cardelli, JA, Green JM, Thomas, MJ, Sorci-Thomas, MG, Orr, AW, Woolard, MD. 2015. Lipin-1 contributes to modified low-density lipoprotein-elicited macrophage pro-inflammatory responses. Atherosclerosis 242; 424-32.

Sorci-Thomas, MG, Pollard, RD, Thomas, MJ. 2015. What does procollagen C-endopeptidase enhancer protein 2 have to do with HDL-cholesteryl ester uptake? Or how I learned to stop worrying and love reverse cholesterol transport? Curr Opin Lipidol. 26:420-5.

Thomas, MJ and Sorci-Thomas, MG. 2015. SAA – A link between cholesterol efflux capacity and inflammation? J. Lipid Res 56: 1383-5.

Liu J, Lu H, Howatt DA, Balakrishnan A, Moorleghen JJ, Sorci-Thomas M, Cassis LA, Daugherty A. 2015. Associations of ApoAI and ApoB-Containing Lipoproteins With AngII-Induced Abdominal Aortic Aneurysms in Mice. ATVB 35: 1826-34.

Pollard, R, Blesso, CN, Zabalawi, M, Fulp, B, Gerelus, M, Zhu, X, Lyons E, Nuradin, N, Francone, OL, Xiang-An, L, Sahoo, D, Thomas, MJ, Sorci-Thomas, MG. 2015. Procollagen C-Endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing SR-BI Mediated HDL-Cholesteryl Ester Uptake. J Biol. Chem. 290: 15496-511.

Chadwick AC, Holme RL, Chen Y, Thomas MJ, Sorci-Thomas MG, Silverstein RL, Pritchard KA Jr. Sahoo D. 2015. Acrolein impairs the cholesterol transport functions of high density lipoproteins.  PLoS One.  10: 123138.

Tavori, H, Su, YR, Yancey, PG, Giunzioni, Wilhelm, AJ, Blakemore, JL, Zabalawi, M, Linton, Sorci-Thomas, MG, Fazio, S. 2015. Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL. J. Lipid Res. Jan 15 [Epub ahead of print]

Gao, M, Zhao, D, Schouteden, S, Sorci-Thomas, MG, Van Veldhoven, P, Eggermont, K, Liu, G, Verfaillie, CM, Feng, Y. 2014. Regulation of HDL on hematopoietic stem/progenitor cells in atherosclerosis requires SR-BI expression. ATVB 34: 1900-1909.

Pollard, R, Samuel, M, Fulp, B, Sorci-Thomas, MG, and Thomas, MJ. 2013. The Conformation of Lipid-Free Apolipoprotein A-I in Solution. Biochemistry 52:9470-9481.

Liu, M, Seo, J, Allegood, J, Bi, X, Zhu, X, Boudyguina, E, Gebre, AK, Shah, D, Sorci-Thomas, MG, Thomas, MJ, Shelness, GS, Spiegel, S, and Parks, JS. 2013. Hepatic apoM stimulates formation of large, S1P-enriched HDL J. Biol. Chem. 289:2801-2814.

Thomas, MJ and Sorci-Thomas, MG. 2013. Why Targeting HDL Should Work as a Therapeutic Tool, but Hasn't. J. Cardiovasc. Pharm. 62;239-246.

Martel, C, Li, W, Fulp, B, Platt, AM, Bittman, R, Tall, AR, Thomas, MJ, Kreisel, D, Swartz, MA, Sorci-Thomas, MG, Randolph, GJ. 2013 Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin. Invest. 123; 1571-1579.

Sorci-Thomas, MG and Thomas, MJ. 2012. High density lipoprotein biogenesis, cholesterol efflux, and immune cell function. Arterioscler Thromb Vas Biol. 32;2561-5.

Sorci-Thomas, MG, Owen, JS, Fulp, B, Bhat, S, Zhu, X., Parks, JS, Shah, D, Jerome, GW, Gerelus, M, Zabalawi, M, Thomas, MJ. Nascent High Density Lipoproteins Formed by ABCA1 Resemble Lipid Rafts and Are Structurally Organized By Three ApoA-I Monomers (2012) J. Lipid Res. 53;1890-909.

Sorci-Thomas, MG, Zabalawi, M, Bharadwaj, MS, Wilhelm, A, Owen, JS, Asztalos, BF, Bhat, S, Thomas, MJ (2012) Dysfunctional HDL Containing L159R ApoA-I Leads to Exacerbation of Atherosclerosis in Hyperlipidemic Mice.  Biochim. Biophys. Acta. 182; 502-12.

Potteaux, S, Gautier, EL, Hutchison, SB, van Rooijen, N, Rader, DJ, Thomas, MJ, Sorci-Thomas. MG, Randolph, GJ. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of ApoE-/- mice during disease regression. (2011) J Clin. Invest. 121:2025-36

Wilhelm, AJ, Zabalawi, M, Shah, D, Owen, JS, Grayson, JM, Major, AS, Bhat, S. Gibbs, Jr, DB, Thomas, MJ, Sorci-Thomas, MG. (2010) Apolipoprotein A-I Results in Increased Regulatory T Cells and Decreased T Cell Activation in Lymph Nodes and Reversal of Lipid Accumulation in the Skin of Diet-fed LDLr-/-, ApoA-I-/-Mice. J Biol Chem.; 285:36158-36169.

Bhat, S, Sorci-Thomas, MG, Calabresi, L, Samuel, M, and Thomas, MJ. (2010) Conformation of Dimeric ApoA-IMilano on Recombinant Lipoprotein Particles. Biochemistry.49(25):5213-24.

Wang, W, Xu, H, Shi, Y, Zhang, H, Gao, H, Weihrauch, D, Feroah, T, Schulte, ML, Jones, DW, Jarzembowski, J, Sorci-Thomas, MG, Pritchard, KA. (2010) Genetic Deletion of Apolipoprotein A-I Increases Airway Hyperresponsiveness, Inflammation and Collagen Deposition in the Lung. J. Lipid Res. (2010) 51:2560-2570.

Wilhelm, AJ, Zabalawi M, Grayson J, Weant, AE, Walzem R, Chan L, Oka K, Owen J, Thomas, MJ, Sorci-Thomas, M.G. Apolipoprotein A-I and its Role in Lymphocyte Cholesterol Homeostasis and Autoimmunity (2009) Arterioscler Thromb Vas Biol. Epub March 12. 29; 843-849.

Sorci-Thomas, MG, Bhat, S, and Thomas, MJ. Activation of Lecithin: Cholesterol Acyltransferase (LCAT) by HDL ApoA-I Central Helices (2009) Future Medicine; Clinical Lipidology, 4:113-124 (2009).

Thomas, MJ, Bhat, S, Sorci-Thomas, MG. Three dimensional models of high density lipoprotein apoA-I: Implication for its assembly and function. (2008) J. Lipid Res. Epub May 30. 49:1875-1883.

Bhat S, Sorci-Thomas MG, Tuladhar R, Samuel MP, and Thomas, M. Conformational Adaptation of ApolipoproteinA-I To Discretely Sized Phospholipid Complexes.  2007 Biochemistry 46;7811-7821.

Owen JO, Bharadwaj MS,, Thomas MJ, Bhat S, Samuel, MP, and Sorci-Thomas MG. Ratio determination  of plasma wild-type and L159R apoA-I using mass spectrometry: Tools for studying apoA-IFin J Lipid Res. 2007 48; 226-234. Epub 2006 Oct 28.

Zabalawi M, Bharadwaj, MS, 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 48;52-65. Epub 2006 Oct 28.

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; 97: 1190-1197.

Thomas, M., and Sorci-Thomas MG. Mass Spectrometry and Solving the Lipid Bound Conformation of ApoA-I” Current Opinion in Lipid.  2006. 17:214-220.

Bhat S, Alexander ET, Sorci-Thomas MG, and 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; 280:33015-33025.

Sorci-Thomas MG. ApolipoproteinA-I helix 6 negatively charged residues attenuate LCAT activation. Biochem. 2005; 44:5409-5419. 

Bhat S, Zabalawi M, Willingham M, Shelness G, Thomas M, Sorci-Thomas MG. .  J. Lipid Res. 2004; 45:1207-1220.2003;163: 1201-1213

Li, H-h. Lyles, DS, Thomas, M.J. Pan, W, Alexander, E. Sorci-Thomas, MG. Apo A-I structure on discs and spheres: Variable helix registry and conformational states. J Biol Chem., 2002; 277:39093-39101.

Sorci-Thomas, MG., Thomas, MJ.  The effects of altered apolipoprotein A-I structure on plasma HDL concentration. In: Trends in Cardiovascular Medicine.  2002;12:121-128.

Schwenke, DC, Rudel, LL, Sorci-Thomas, MG, Thomas, MJ. Alpha tocopherol and polyunsaturated fats protect against diet induced atherosclerosis in New Zealand white rabbits. J. Lipid Res. 2002; 43:1927-1938.

Reschly, ER, Sorci-Thomas, M, 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; 277: 9645-9654.

  Lab Members

Hao Xu, PhDHao Xu, PhD

Lab Supervisor

xuhao@mcw.edu
(414) 955-5734

 

Sushma Kaul, PhDSushma Kaul, PhD

Research Associate

skaul@mcw.edu
(414) 955-5731

 

Katherine FredrichKatherine Fredrich

Research Associate

kfredrich@mcw.edu

(414) 955-5730

 

Kaniz FatemaKaniz Fatema

Research Technologist

kfatema@mcw.edu
(414) 955-8099

 

  Secondary Appointments
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