Peisong Ma Research

My lab research focuses on megakaryopoiesis, thrombosis, and hemostasis, with a special emphasis on understanding G-protein coupled receptor (GPCR)-mediated platelet activation and thrombus formation. Our recent studies provide novel insights into the regulatory mechanisms that fine-tune platelet responses to vascular injury. Using CRISPR-Cas9 genome editing, induced pluripotent stem cells (iPSCs), well-established vascular injury models, and various biochemical approaches, we have demonstrated that GPCR kinases (GRKs) play a critical role in hemostasis by modulating GPCR signaling in platelets. More recently, we identified that a common GRK5 variant, found in 5 million Americans, is associated with reduced GRK5 expression in platelets, heightened platelet activation, and an increased risk of cardiovascular diseases, including pulmonary embolism and stroke.

Our GWAS analysis in humans and findings from platelet studies in Grk5^-/- mice provide strong evidence that GRK5 is a critical negative regulator of platelet activation via PAR1. These findings support the proposed model that GRK5 could be manipulated to manage platelet dysfunction in diseases, including stroke and VTE.

Current studies are investigating novel positive regulators and negative regulators in response to GPCR-coupled agonists using genome-wide CRISPR-Cas9 screen. 

GRKs are essential regulators of GPCR signaling in megakaryopoiesis and thrombopoiesis. Insights gained will provide a molecular framework for selectively targeting GRK-mediated pathways, potentially opening new avenues for therapeutic interventions to modulate platelet production in patients with various acquired and inherited platelet disorders.