Walter P. Jeske, PhD Associate Professor Departments of Pathology and Thoracic & Cardiovascular Surgery Hemostasis and Thrombosis Research Laboratories (708) 327-2842 WJESKE@lumc.edu

Pathophysiology Of Vascular Disorders And Their Modulation By Novel Pharmaceuticals

Platelets play a key role in arresting bleeding, promoting blood clot formation, and may link the hemostatic and inflammatory systems through the release of cytokines and through interaction with leukocytes. This is especially important in light of the increased incidence of lifestyle-induced cardiovascular disease in industrialized countries.

Research and teaching activities focus on measuring platelet activation in a variety of clinical conditions and the ability of pharmaceutical agents (e.g., GP IIb/IIIa inhibitors, ADP receptor blockers) to modulate various aspects of the activation process. The primary focus of the lab is on understanding the pathophysiologic mechanisms involved in heparin-induced thrombocytopenia (HIT), a potentially serious immunologic reaction to heparin therapy that can be paradoxically associated with thrombotic complications. It is currently accepted that antibodies generated in HIT activate platelets. Studies in the lab are carried out to determine whether these antibodies also promote leukocyte and endothelial activation and how such activation impacts the overall prothrombotic environment in HIT.

Flow cytometry is powerful technique commonly employed in the laboratory to quantitate platelet activation and platelet-leukocyte interactions. This technique has been applied to characterize platelet activation and platelet interaction with leukocytes in a.) patients with HIT, b.) patients undergoing coronary bypass surgery with a right ventricular assist device, c.) patients receiving intracoronary brachytherapy or drug eluting stents following percutaneous coronary intervention and d.) patients treated with selective serotonin reuptake inhibitors for symptoms of depression. In addition, this technique is applied to basic science studies examining the pharmacodynamics of novel antiplatelet agents, the effect of HMG-CoA reductase inhibitors (statins) on platelet activation and how the interaction of platelets with monocytes impacts monocyte activation through a specific adenine nucleotide receptor.

A second research focus relates to the pharmacology of heparin and related glycosaminoglycan drugs. Such studies include modeling the pharmacokinetic profile of low molecular weight (LMW) heparins, characterizing differences between LMW heparins, examining the pharmacology and structure-activity relationships of heparins isolated from novel sources (such as fish skin) and studying the pharmacology of modified dermatan sulfate derivatives.

Graduate Student and Resident Participation

Residents, medical students, graduate students, and undergraduate students are encouraged to participate in any of the ongoing research projects.

Publications

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