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Nieman's research program seeks to define the assembly of receptor complexes and determine how they work together at the molecular level to mediate physiological responses. Since 2007, his laboratory has focused on identifying the key factors that determine the efficiency of thrombin signaling through protease activated receptor 4 (PAR4) on platelets and other cells. The laboratory has used a range of approaches from biochemistry and structural biology to mouse models to address these questions.

In addition to their role in hemostasis, platelets cooperate with neutrophils, monocytes and tumor cells to influence the behavior of these cells in a variety of physiological and pathophysiological conditions. A second focus of his research program is to identify the mechanisms by which platelets adhere to and communicate with these multiple cell types using both in vitro and in vivo approaches.

The underlying theme of his research program is that protease-activated receptors (PARs) interact with other G-protein coupled receptors in the cell membrane to mediate the full range of protease signaling. Thrombin is a potent platelet agonist that signals through PAR1 and PAR4 to mediate adhesion and aggregation. PAR4 is associated with a prolonged stimulus as measured by intracellular Ca2+-mobilization and is required for stable clot formation. The rate of PAR4 activation by thrombin is enhanced ~10 fold due to a PAR4 heterodimerization with PAR1. Heterodimerization is a common theme for regulating signaling. Three major platelet GPCRs (PAR1, PAR4, P2Y12) allosterically regulate their signaling through heterodimerization. His current projects are using structural biology to determine how these receptors assemble into multiprotein complexes to influence how they interact with agonists and downstream signaling machinery. Nieman and his team use animal models of disease to determine how these protein complexes work in vivo.