As vice provost and dean for graduate studies, Nieman provides strategic leadership to support graduate student success in research and teaching, as well as holistic guidance for well-being and career development. Professor Nieman has held many leadership roles on campus and nationally, including in the National Directors of Graduate Studies and through his help founding the ÐÇ¿Õ´«Ã½ chapter of the Society for Advancing Chicanos/Hispanics and Native Americans.
Nieman is also a professor of pharmacology and most recently served as the School of Medicine’s vice dean for graduate education.
Our lab studies platelet signaling and crosstalk with the immune system in thrombosis and cancer. More specifically, we focus on how proteases initiate intracellular signaling through protease activated receptors. We use structural biology, cell signaling, and animal models to uncover molecular mechanisms then verify these in vivo.
Research Information
Research Interests
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.
Awards and Honors
Professional Memberships
Publications
Peer Reviewed Publications (selected)
- Sekhon U, Swingle K, Luc N, Girish A, de la Fuente M, Shah K, Kim Y, Eppel S, Capadona J, Shoffstall A, Nieman MT, Sen Gupta A. Procoagulant synthetic platelets (P-SP) for augmenting hemostasis in bleeding dysfunctions. Sci. Transl. Med. 2021; 16. doi: 10.1126/scitranslmed.abb8975
- Stoller ML, Basak I, Denorme F, Rowley JW, Alsobrooks J, Parsawar K, Nieman MT, Yost CC, Hamilton JR, Bray PF. Campbell RA. Neutrophil cathepsin G proteolysis of protease-activated receptor 4 generates a novel, functional tethered ligand. Blood Adv. 2022 6:2303-2308. doi: 10.1182/bloodadvances.2021006133.
- de la Fuente M, Han X, Miyagi M, Nieman MT. Expression and Purification of Protease-Activated Receptor 4 (PAR4) and Analysis with Histidine Hydrogen-Deuterium Exchange. Biochemistry. 2020; 59:671-681. doi: 10.1021/acs.biochem.9b00987 PMCID: In progress.
- Han X, Hofmann L, de la Fuente M, Alexander N, Palczewski K, INVENT Consortium, Nieman MT. PAR4 activation involves extracellular loop-3 and transmembrane residue Thr153. Blood. 2020; 136:2217-2228. PMCID: PMC7645988.
- Han X, de le Fuente M, Nieman MT. Complement factor C4a does not activate protease activated receptor 1 (PAR1) or PAR4 on human platelets. Res Pract Thromb Haemost. 2021; 5:104-110.
- Bouck EG, de le Fuente M, Zunica ER, Li W, Mumaw MM, Nieman MT. Cadherin-6 mediates thrombosis in vivo. Res Pract Thromb Haemost. 2021; 5:125-131.
- Han X, Knauss EA, Fuente M, Li W, Conlon RA, LePage DF, Jiang W, Renna SA, McKenzie SE, Nieman MT. A Mouse Model of the Protease Activated Receptor 4 (PAR4) Pro310Leu Variant has Reduced Platelet Reactivity. J. Thromb. Haemost. 2024: doi: 10.1016/j.jtha.2024.03.004. Online ahead of print.
Invited Reviews (peer reviewed)
- Han X, Nieman MT, Kerlin BA. Protease Activated Receptors-An illustrated Review, Res Pract Thromb Haemost. 2021; 5:17-26. Corresponding Author. PMCID: PMC7845062.
Invited Book Chapters (peer reviewed)
- Han X, Aiyer S, Ismail J, Nieman MT, Protease Activated Receptors (PARs), Encyclopedia of Molecular Pharmacology. 2021
Invited Editorials
- Nieman MT and Neeves K. Flipping the script: Defining the reversibility of platelet activation. J. Thrombos. Haemost., 2023;21:1102-1103. doi: 10.1016/j.jtha.2023.02.003.
- Knauss EA and Nieman MT. Glycoprotein exerts local control over fibrin. Nature Cardiovasc. Res. 2023;2:335-336.
- Nieman MT. Biased signaling on the move. Blood. 2024;143:835-836.