Faculty

Silvia Pierangeli, Ph.D.

Professor
sspieran@utmb.edu
Route 1165
Departments of Internal Medicine-Rheumatology and Microbiology & Immunology
Phone: (409)772-0222

Education:	Ph.D. | 1990 | University of Louisville, Louisvill, KY
	Ph.D. (Doctorate Degree) | 1989 | Buenos Aires National University, Bueno Aires, Argentina
	M.S. | 1987 | University of Louisville, Louisville, KY
	B.S. | 1979 | Buenos Aires National University, Buenos Aires, Argentina

Overview

Pathogenesis of thrombosis in the Antiphospholipid Syndro. Dr. Pierangeli’s research interests are on Antiphospholipid Syndrome (APS) and lupus. Her laboratory is well-funded and is working on the pathogenic mechanisms to explain thrombosis in APS.

Research Interests

Antiphospholipid Syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibodies that react with phospholipids (antiphospholipid antibodies) and phospholipid-binding proteins of the coagulation cascade. Clinical manifestations of the disease include: recurrent arterial and/or venous thrombosis and pregnancy loss among other symptoms. APS can also be found in a significant proportion of patients with lupus. Thrombosis is a devastating consequence in patients with APS and SLE.

Activation of endothelial cells, monocytes and platelets has been accepted as one of the major pathogenic mechanisms to explain thrombosis in APS. Antiphospholipid antibodies recognize β2Glycoprotein I (β2GPI), a plasma glycopoprotein that binds to endothelial cells and eventually trigger an intracellular signaling and a pro-coagulant and pro-inflammatory phenotype [including expression of tissue factor (TF), vascular cell adhesion molecule (VCAM-1)] and other markers of inflammation. The nature of the receptor recognized by antiphospholipid antibodies is unknown.

Our interests are currently focused on studying intracellular mechanisms triggered by antiphospholipid antibodies on target cells (monocytes, endothelial cells and platelets) and to identify the receptor(s) recognized for these antibodies on those cells. Annexin A2 has been shown to bind β2GPI in endothelial cells, and there is evidence that toll-like receptor-4 (TLR-4) and possible the receptor for apolipoprotein E2’ are also involved. We hypothesize that β2GPI may bind to receptor protein(s) in target cells and the signalling may occur in association with other proteins upon binding of the specific autoantibodies. We are conducting studies to examine those questions in vitro and in vivo. We are utilizing a unique mouse model of induced thrombosis. We are also currently measuring TF activities in various tissues of the mice, and utilizing state-of-the-art quantum dot technology to measure expression of adhesion molecules and TF in aortas of mice by dual photon confocal microscop (in collaboration with the Center for Biomedical Engineering at UTMB). In our in vitro experiments, we utilize tissue culture, RT PCR, western blot and other molecular techniques such as analysis of RNA transcriptome from material extracted from cultured endothelial cells and from monocytes of APS patients and controls. For our in vivo experiments we use a wide variety of knock out and transgenic strains of mice (including annexin A2, TLR-4, apoER2’ deficient mice and specific soluble inhibitors to be used in our in vitro and in vivo experiments).

Understanding the molecular mechanisms triggered by antiphospholipid antibodies in target cells and the receptor(s) recognized by these antibodies will help us in the development of new targeted therapies to ameliorate and/or prevent clinical manifestations of APS.

• Our laboratory is also involved in studies to determine the influence of MHC class II haplotypes on the production of pathogenic antiphospholipid antibodies utilizing a well-established mouse model to induce APS by active immunization with β2GPI (these studies are done in collaboration with Dr Christadoss in Microbiology).
• In collaboration with Drs. Doruk Erkan and Michael Lockshin, we are conducting a pilot clinical study to examine the effects of the statins on proinflammatory/prothrombotic markers with APS.
• In collaboration with Dr. Firoze Khan (Department of Pathology) we are conducting studies to evaluate oxidative stress in patients with lupus.
• In collaboration with the Rheumatology Division at TMC UT Houston, we are evaluating mechanisms by which hydroxychloroquine exerts beneficial effects in patients with lupus and with APS (using resources from the multiethnic LUMINA cohort/registry).

Recent Publications

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