Qin Chen

Publications of Qin Chen

• Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1.

  Authors: Margitta Elvers, David Stegner, Ina Hagedorn, Christoph Kleinschnitz, Attila Braun, Marijke E J Kuijpers, Michael Boesl, Qin Chen, Johan W M Heemskerk, Guido Stoll, Michael A Frohman, Bernhard Nieswandt

  Science signaling. 01/2010; 3(103):ra1.

  Platelet aggregation is essential for hemostasis but can also cause myocardial infarction and stroke. A key but poorly understood step in platelet activation is the shift of the principal adhesivePlatelet aggregation is essential for hemostasis but can also cause myocardial infarction and stroke. A key but poorly understood step in platelet activation is the shift of the principal adhesive receptor, alpha(IIb)beta(3) integrin, from a low- to high-affinity state for its ligands, a process that enables adhesion and aggregation. In response to stimulation of heterotrimeric guanosine triphosphate-binding protein or immunoreceptor tyrosine-based activation motif-coupled receptors, phospholipases cleave membrane phospholipids to generate lipid and soluble second messengers. An essential role in platelet activation has been established for phospholipase C (PLC) but not for PLD and its product phosphatidic acid. Here, we report that platelets from Pld1(-/-) mice displayed impaired alpha(IIb)beta(3) integrin activation in response to major agonists and defective glycoprotein Ib-dependent aggregate formation under high shear conditions. These defects resulted in protection from thrombosis and ischemic brain infarction without affecting tail bleeding times. These results indicate that PLD1 may be a critical regulator of platelet activity in the setting of ischemic cardiovascular and cerebrovascular events.

• Targeting phospholipase D with small-molecule inhibitors as a potential therapeutic approach for cancer metastasis.

  Authors: Wenjuan Su, Qin Chen, Michael A Frohman

  Future oncology (London, England). 11/2009; 5(9):1477-86.

  Phospholipase D (PLD)1 and PLD2, the classic mammalian members of the PLD superfamily, have been linked over the past three decades to immune cell function and to cell biological processes requiredPhospholipase D (PLD)1 and PLD2, the classic mammalian members of the PLD superfamily, have been linked over the past three decades to immune cell function and to cell biological processes required by cancer cells for metastasis. However, owing to the lack of effective small-molecule inhibitors, it has not been possible to validate these roles for the PLDs and to explore the possible utility of acute and chronic PLD inhibition in vivo. The first such inhibitors have recently been described and demonstrated to block neutrophil chemotaxis and invasion by breast cancer cells in culture, increasing the prospects for a new class of therapeutics for autoimmune disorders and several types of metastatic cancer.