1. Mechanisms of antigen-antibody recognition in Antiphospholipid Syndrome. Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder characterized by vascular thrombosis and pregnancy morbidity.  Years of clinical research have shown that antiphospholipid antibodies cause vascular events in APS patients.  Yet, how antiphospholipid antibodies cause disease remains unknown.  Our laboratory studies how antiphospholipid antibodies interact with protein antigens, specifically beta-2 glycoprotein I and prothrombin, at the atomic and molecular level, providing the structural basis to understand the mechanisms underlying thrombosis and new ways to intervene.

2. Thiol-isomerases in Antiphospholipid Syndrome.  Thiol-isomerases (TIs), also known as endoplasmic reticulum proteins (ERps) or protein disulfide isomerases (PDIs), constitute a large family of enzymes essential for life.  Intracellularly, PDIs are responsible for oxidative protein folding and, in general, cell homeostasis.  Extracellularly, PDIs play important regulatory roles, most notably in thrombus formation.  They also participate in immunological responses by supporting antigen presentation and by modulating the function of plasma proteins recognized by antiphospholipid antibodies.  Our laboratory explores the structure, function, and allosteric regulation of TIs, especially in the context of APS.  Our goal is to identify the structural and mechanistic basis of substrate specificity and develop TIs’ specific and potent molecules to modulate their function with potential use in several clinical applications, including thrombosis.