Peisong Ma Research
Contact
1020 Locust Street, Room 394
Philadelphia, PA 19107
Highlighted Publications
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.
Publications
- Argonaute2 modulates megakaryocyte development and sex-specific control of platelet protein expression and reactivity
- Nuclear Receptors in Platelet Activation and Thrombosis in Hypercholesterolemia
- Phosphatidylserine-blocking nanoparticles inhibit thrombosis without increased bleeding in mice
- Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential
- A regulatory node involving Gαq, PLCβ, and RGS proteins modulates platelet reactivity to critical agonists
- Novel Strategy to Combat the Procoagulant Phenotype in Heparin-Induced Thrombocytopenia Using 12-LOX Inhibition
- GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12
- Human and mouse PAR4 are functionally distinct receptors: Studies in novel humanized mice
- G protein–coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1
- High-efficiency unassisted transfection of platelets with naked double-stranded miRNAs modulates signal-activated translation and platelet function
- RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival
- The roles of GRKs in hemostasis and thrombosis
- GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets
- RGS10 shapes the hemostatic response to injury through its differential effects on intracellular signaling by platelet agonists
- A systems approach to the platelet signaling network and the hemostatic response to injury
- Modulating platelet reactivity through control of RGS18 availability
- Dissociation of SHP-1 from spinophilin during platelet activation exposes an inhibitory binding site for Protein Phosphatase-1 (PP1)
- Applying the brakes to platelet activation
- A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling
- Platelet signaling