Peisong Ma, PhD
Philadelphia, PA 19107
(215) 955-9170 fax
National University of Singapore, Singapore - 2004
University on Pennsylvania
Dr. Ma’s laboratory is involved with investigations in the areas of thrombosis and hemostasis, with a special emphasis on understanding GPCR (G-protein coupled receptor) and G-protein mediated platelet activation. Our current studies provide novel insights into the regulatory mechanisms that allow platelets to produce an optimal response to vascular injury. Using well-established vascular injury models, CRISRP-Cas9 genome-editing and biochemical approaches, we have provided strong evidence that defects in GPCR and G-protein signaling pathways translate into in vivo phenotypes. The following is a brief summary of major ongoing projects in the lab.
Project 1: RGS-insensitive Gq (G188S) as probes of G protein Functions
We recently develop a mutant mouse line with a mutation (G188S) in Gq subunit that renders the G protein resistant to interaction with RGS (regulator of G protein signaling) proteins as a class. In contrast to enhanced Gi2 signaling in Gi2(G184S) mutant platelets, we have observed decreased platelet activation in Gq(G188S) mutant mice, suggesting that the negative feedback of Gq regulation is different from that of Gi2. An ongoing study is to fully characterize the effect of G188S mutation on platelet function and thrombus formation.
Project 2: The signaling machinery that provides negative feedback regulation to G protein-dependent signaling during platelet activation
Using CRISPR-Cas9 genome editing, we have recently determined that multiple components of the platelet-signaling network are integrated to mediate GPCRs and G protein-dependent pathways. Ongoing studies are to characterize the mechanisms by which these molecules impact platelet functions, thrombus formation both in vitro and in vivo. To accomplish these goals, we make use of several recently generated mutant mouse lines, intravital microscopy approach and other biochemical techniques.
Project 3: The regulatory networks that regulate platelet activation downstream of G protein signaling using Genome-wide screening
We established that αIIbβ3 activation as readout for genome-wide pooled CRISPR-Cas9 screen in primary megakaryocytes. We will identify novel positive regulators and negative regulators that control integrin activation in response to GPCR-coupled agonists.
Most Recent Peer-Reviewed Publications
- 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)
- Platelet signaling
- 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
- Regulating thrombus growth and stability to achieve an optimal response to injury
- Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin (Journal of Cell Biology (2006) 174, 7, (1097-1106))
i2αinteractions modulate platelet accumulation and thrombus formation at sites of vascular injury
- Focus on Molecules: Lacritin
- Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin
- Restricted epithelial proliferation by lacritin via PKCα-dependent NFAT and mTOR pathways
- Characterization of the seabass pancreatic α-amylase gene and promoter
- Hormonal influence on amylase gene expression during Seabass (Lates calcarifer) larval development
- Erratum: Hormonal influence on amylase gene expression during Seabass (Lates calcarifer) larval development (General and Comparative Endocrinology (2004) 138 (14-19) DOI: 10.1016/j.ygcen.2004.04.007)
- Ontogeny of α-amylase gene expression in sea bass larvae (Lates calcarifer)