Staff Collaborate Conference Room

Mary Sorci-Thomas, PhD

marysorcithomas

Mary Sorci-Thomas, PhD

Professor, Medicine (Endocrinology)

Locations

  • Endocrinology

Contact Information

Research Interests

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