Michael Holinstat, PhD
Philadelphia, PA 19107
(215) 955-9170 fax
Most Recent Peer-reviewed Publications
- Dichotomous effects of exposure to bivalirudin in patients undergoing percutaneous coronary intervention on protease-activated receptor-mediated platelet activation
- Investigations of human platelet-type 12-lipoxygenase: Role of lipoxygenase products in platelet activation
- Protein kinase C regulation of 12-lipoxygenase-mediated human platelet activation
- Rap1-Rac1 circuits potentiate platelet activation
- We can do it together: PAR1/PAR2 heterodimer signaling in VSMCs
Research and Clinical Interests
My lab focuses on understanding the complex signaling underlying small GTPases that regulate normal vascular hemostasis. Small G proteins are composed of one subunit (alpha) which is continuously cycling between an inactive (GDP) and active (GTP) form. In the active form, small G proteins regulate a number of physiologically crucial processes. Specifically, we are interested in how Rap1, a small G protein central to activation of integrins in platelets, is regulated through the various receptor activation pathways. Since activation of all of these pathways eventually lead to activation of Rap1, elucidating the mechanisms by which Rap1 is activated, inactivated and propagates its signal may allow for the development of novel anti-platelet therapies for the treatment of thrombosis leading to vessel occlusion and stroke.
Rap1 function in cardiovascular disease.
Cardiovascular disease (CVD) is the leading cause of death globally and nearly 50% of men and 35% of women will be diagnosed with a cardiovascular disease by age 40. CVD and Diabetes lead to a shift in the threshold for platelet activation. Currently, it is unclear what the mechanisms regulating this shift toward a pro-thrombotic state are. We are investigating how the progression of these vascular disorders may alter the signaling of Rap1 as well as other small G proteins that regulate platelet function. Identifying where these signaling modifications are taking place will allow for better treatment of people suffering from these and possibly other related vascular disorders such as edema and DVT.