Oxylipins are the key for the development of novel antiplatelet drugs to prevent clotting

Michael Holinstat, PhD
University of Michigan

Abstract: Cardiovascular disease remains the primary cause of morbidity and mortality and platelet activation is critical for maintaining hemostasis and preventing leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the enzyme 12-lipoxygenase (12-LOX) was demonstrated to be a key regulator of platelet function and targeting 12-LOX has now been shown by our group to be a viable approach to prevent clotting in the blood known as thrombosis. Subsequently, our group has evaluated several o12-LOX oxylipins including 12-HETrE, 12-HEPE, and 11/14- HODE. 12-HETrE, produced in the platelet, was shown to limit platelet reactivity through activation of the prostacyclin receptor. We have now demonstrated that an analogue of 12-HETrE, known as CS585, may have clinical utility in prevention of thrombotic diseases. We will discuss the advances in identification and development of novel targets to prevent platelet activation and thrombosis in the blood and how we translate these findings from the bench to the clinic.

Biography: Dr. Michael Holinstat is a professor in the department of pharmacology and a fellow of the American Heart Association. Dr. Holinstat’s research interests focus on understanding lipid, lipoxygenase, and oxygenase regulation of platelet signaling and function and how it relates to regulation of hemostasis and thrombosis. He serves as the inaugural Director of the Platelet Physiology and Pharmacology Platelet Core at the University of Michigan. Additionally, Dr. Holinstat serves on several national boards including the sub-committee on Hemostasis and Thrombosis at the American Society for Hematology and the Director for the NIH CTSI-funded T32 training grant in clinical research. Dr. Holinstat has received several national awards including the Kenneth M. Brinkhous Young Investigator Prize in Thrombosis from the Council on Arteriosclerosis, Thrombosis, and Vascular Biology in 2012 and the Young Investigator Award in Structure-Function from the Eicosanoid Research Foundation in 2013. Dr. Holinstat has received numerous patents from the US, EU, and Japan patent offices for various therapeutic discoveries to treat cardiovascular disease. In addition to his NIti-funded research, Dr. Holinstat continues to translate his discoveries into potential clinical application through collaborations with Veralox Therapeutics, Cereno Scientific, and Lexicon Pharmaceuticals. Dr. Holinstat has published over 100 peer-reviewed publications in the area of platelet biology and lipids and his work is highly cited with an H-index of 43. Dr. Holinstat has spent the last 20 years training the next generation of clinical and translational scientists in the area of blood clotting, platelet biochemistry, and discovery of novel therapeutic approaches for treating thrombosis including undergraduates, graduate students, postdoctoral fellows, clinical fellows, and basic and clinical faculty.