Debra A. Hoppensteadt-Moorman, PhD Associate Professor Department of Pathology Technical Director of the Hemostasis and Thrombosis Research Program (708) 216-4625 dhoppen@lumc.edu

As the Technical Director of the Hemostasis and Thrombosis Research Laboratories, Dr. Hoppensteadt-Moorman is responsible for the overall operation of the laboratories including basic, clinical, and research output. These laboratories are involved in the central development and validation of newer methods to investigate the mechanisms in the pathogenesis of vascular and thrombotic disorders. In addition, by using immunologic, biochemical, and molecular techniques, the effects of newer drugs on the hemostatic and thrombotic processes are also studied.

The basic research work in this laboratory focuses on two major areas: The first deals with the role of tissue factor pathway inhibitor (TFPI) in the modulation of thrombogenesis with particular reference to vascular pathology. To accomplish this, methods (both functional and immunologic ) have been developed to quantitate TFPI and it variants in both plasma and cell culture. The regulation of TFPI by drugs, such as heparin and polydeoxyribonucleotides (aptamers) and the polyelectrolytes, has been investigated in animal models and cell cultures. Utilizing plasma samples from clinical trials, the role of TFPI in the control of restenosis regulation of the mediators and antithrombotic actions are being studied. Recombinant variants of TFPI, chemically or enzymatically digested fragments of TFPI, are also used to investigate the interaction of TFPI with tissue factor, factor Xa, and Factor VII-TF complex. This research is directed to investigate the pathogenesis of coronary artery disease. Blood plasma samples from well-defined clinical cases are obtained to profile the TFPI that is released. Other pathologic states include stroke, transplantation-associated vasculopathies, hepatic transplantation, and pregnancy-associated hypercoagulable states.

The second major area of research is directed in the study of the mechanism of hypercoagulable state and thrombogenesis in autoimmune diseases. To accomplish this, a major program has been developed to investigate the pathogenic mechanisms in antiphospholipid syndrome (APS). The antibodies in APS are characterized in terms of their functional interactions with cellular membranes and the activation profile in studies using flow cytometric methods, mediator/cytokine generation assays, and other interactions with blood and vascular cells. The pathogenesis of APS is also characterized in terms of vascular dysfunction/endothelial distress. Specific methods to investigate the role of oxidative stress, PAI upregulation, adhesion molecules (ICAM,VCAM, selectins), and thrombomodulin are probed. Newer techniques to diagnose the APS are developed. These antibodies are also isolated, purified, and characterized in terms of their effects on the activation of cellular processes. The effects of APS antibodies on cultured cellular expression of various cytokines are also investigated..

The clinical Hemostasis and Thrombosis Research Program is focussed on the markers of the newer antithrombotic and antiplatelet drugs to optimize therapeutic usage. Furthermore, an effort is made to understand the mechanism involved in the mediation of myocardial infraction, acute coronary syndrome, cardiovascular ischemia, and bone marrow vasculopathies. Such drugs as the low molecular weight heparins (LMWHs), antithrombin drugs, antiplatelet drugs, and anti-Xa agents are investigated. The pathogenesis is also investigated in terms of the release of specific markers of coagulation, fibrinolytic deficit, platelets, and vascular dysfunction. A close collaboration with the Liver Transplant Unit at Loyola and with the Department of Cardiology has been developed to secure samples of well-defined cases. A serum/plasma bank has also been set up. The service components of Dr. Hoppensteadt-Moorman's activities include the monitoring of new drugs, consultation on difficult diagnoses, interpretation of results of specialized tests, and direct consultation about the management of patients who are taking some of these newer drugs. Her laboratory also provides instrument/new method validation and works closely with pharmaceutical and device industry to develop new drugs and therapeutic/diagnostic devices.

Publications:

View a partial list of Dr. Hoppensteadt's publications through the National Library of Medicine's PubMed online database.