Areas of Research

We are working with Cereno Scientific on the preclinical development program for the small molecule CS585, hoping to start clinical phase 1 studies in 2023. CS585 is a stable and selective IP receptor agonist that we expect to greatly impact the cardiovascular field. 

https://cerenoscientific.com/pipeline/preclinical-programs/ 

CS014 is a novel HDAC inhibitor that regulates platelet activity. The figure above shows the inhibition of thrombosis in a laser-induced thrombosis assay. Our lab is currently working with Cereno Scientific on moving this drug into phase 2 clinical trials. 

Read more about it in this abstract 

The lab also focuses on novel oxidized lipids (oxylipins) formed in the human platelet and their effects on hemostasis and thrombosis. We have identified that 12-LOX oxidizes some 0mega-6 fatty acids to produce a novel eicosanoid, 12-HETrE. This is a potent inhibitor of platelet function. This project works on elucidating the underlying mechanisms by which 12-HETrE protects against platelet activation, clot formation, and stroke. 

Read more about it here!

Another project in the lab focuses on the enzyme 12-lipoxygenase (12-LOX) regulates platelet activation. Similar to COX-1, 12-LOX oxidizes free fatty acids to form bioactive metabolites (called eicosanoids). Our lab has recently shown that the 12-LOX eicosanoids derived from arachidonic acid in the platelet are pro-thrombotic and we, along with our collaborators, have developed the first selective inhibitor against human 12-LOX activity! This new class of inhibitors prevents agonist-mediated platelet activation and clot formation in human platelets. 

Learn more about it here. 

One of the newer projects in the lab focuses on identifying active compounds found in herbal extracts used to treat cardiovascular diseases in Chinese medicine. We are working to isolate compounds that have a direct effect on platelets to uncover novel therapeutics in the treatment of cardiovascular-related diseases. 

This project focuses on identifying the inherent racial differences in platelet function between African Americans and Caucasian Americans by investigating some of the underlying genetic differences in blacks and whites, which predisposes some people to a higher risk for thrombosis and stroke while sparing others.

Through this effort, we hope to determine, for the first time, how to treat patients based on their genetic/racial background. This area of research often termed “personalized or precision medicine”, has the potential to shift our mode of treatment from disease to patient by understanding that not all treatments will equally benefit every patient.  More importantly, we want to prevent thrombotic events that may differ based on genetic or racial background. This study has shown that blacks express a polymorphism in the thrombin receptor PAR4, which is hyperactive compared to whites. In addition, we have uncovered a novel protein in the human platelet (absent in the mouse platelet), phosphatidylcholine transfer protein (PCTP), which may play a role in platelet activation and is highly expressed in platelets from blacks compared to whites.

Learn more here