Peisong Ma Research

Yarman Y, Zhao X, Ahn H, Thomson HA, Sarkar A, Yuan T, Roberts ME, Wurtzel J, Diamond SL, Tesmer JJG, French DL, Tomaiuolo M, Turro E, Astle W, Goldfinger LE, McKenzie SE, Benovic J, Stalker TJ, Poncz M, Ma P. Understanding how a highly prevalent GRK5 polymorphism affects platelets and enhances thrombotic risk. Blood. 2026 PMID: 41557909.

We identify GRK5 as a previously unrecognized regulator of thrombin/PAR1 signaling and provide the first experimental evidence linking this common A→G variant to enhanced thrombin signaling and increased thrombus formation in vivo. Using human GG donor platelets, iPSC-derived megakaryocytes, GRK5 inhibition, a humanized mouse model, and two preclinical models, we connect human genetics → platelet GPCR regulation → stroke and venous thromboembolism risk.

Zhao X, Cooper M, Michael JV, Yarman Y, Baltz A, Chuprun JK, Koch WJ, McKenzie SE, Tomaiuolo M, Stalker TJ, Zhu L, Ma P. GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12. Blood Adv. 2022 Jun 17. PMID: 35793439.PMCID: PMC9636328

We have demonstrated, for the first time, that GRK2 functions as a critical negative regulator in platelet activation and modulates the hemostatic response to injury. It does so by limiting ADP P2Y₁ and P2Y₁₂-mediated signaling. Collectively, the information gained from this study should enable better development of GRK2-based therapeutic options for treatment of cardiovascular disease and thrombotic disorders.

Downes K, Zhao X, Gleadall NS, McKinney H, Kempster C, Batista J, Thomas P, Cooper M, Michael J, Kreuzhuber R, Wedderburn K, Waller K, Varney B, Kriek N, Ashford S, Stirrups K, Dunster, J, McKenzie S, Ouwehand WH, Gibbins JM, Yang J, Astle WJ, Ma. P. G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR1. Blood Adv. 2022. Apr 12;6(7):2319-2330. PumMed PMID: 34581777. PMCID: PMC9006276.

We have demonstrated for the first time that GRK5 regulates thrombin signaling in human platelets via PAR1. Decreased GRK5 expression leads to increased risk of pulmonary embolism and venous thromboembolism.

Chen X, Gupta S, Cooper M, DeHelian D, Zhao X, Naik MU, Wurtzel JGT, Stalker TJ, Goldfinger LE, Benovic J, Brass LF, McKenzie SE, Naik UP, Ma P. GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets. Blood Adv. 2020 Jan 14;4(1):76-86. PubMed PMID: 31899801.    

We, for the first time, show that GPCR kinases (GRKs) are critical negative regulators during platelet activation.