Bergmeier lab, 10th Symposium on Hemostasis; Chapel Hill — Spring 2022
Bergmeier Lab research
Bergmeier lab employs a multidisciplinary approach (biochemistry, cell and molecular biology, immunology, cutting-edge microscopy and animal models) to investigate how stem cells turn into a unique blood cell, the Platelet, and how altered platelet function contributes to human disease. Platelets are small anucleate blood cells that are best known for their ability to help us stop bleeding when we are injured. Platelets drive the formation of a hemostatic plug through a complex process involving G-protein coupled receptors, calcium-mediated signaling, cytoskeletal remodeling, integrin-mediated adhesion, and apoptosis. Dysregulation of these processes in platelets may contribute to the onset and progression of various bleeding disorders, thrombosis, and cancer.
Dr. David Paul, Bergmeier Lab Published: Journal of Thrombosis and Haemostasis
Fig 2E. shows one of the key findings of the paper: P2Y1 receptor-mutant mice (red lines) fail to desensitize to repeated ADP stimulation, compared to mice with wild-type P2Y1receptor (black lines).
Hemostatic plug formation at sites of vascular injury is strongly dependent on rapid platelet activation and aggregation. However, to prevent thrombotic complications, platelet aggregate formation is regulated, in part, by the desensitization of the platelet P2Y1 receptor. Here, we analyzed a novel knock-in mouse strain expressing a P2Y1 receptor variant that cannot be desensitized.
First author, David S. Paul PhD, Research Assistant Professor
The study, led by David S. Paul and Tasha Blatt, demonstrates that loss of P2Y1 receptor desensitization in platelets leads to increased P2Y1 receptor signaling in vitro, with little impact on in vivo platelet adhesion/aggregation at sites of vascular injury, likely due to rapid ADP degradation or being swept away in the bloodstream.
This research project was a collaborative effort supported by senior authors, Dr. Wolfgang Bergmeier of the UNC Blood Research Center (BRC), UNC Biochemistry and Biophysics, and Dr. Robert Nicholas of the UNC Pharmacology. Other contributing BRC members include former *research staff: Wyatt Schug, Emily G. Clark, Katie Poe; and Drs. Jean Marie N. Mwiza, Tomohiro Kawano, and Nigel Mackman.
Wyatt Schugg is enrolled in grad school to earn his PhD at Univ. of VA., Emily “Gracie” Clark is enrolled in graduate school to earn her PhD at University of North Carolina at Chapel Hill, Katie Poe now works at a biotech firm in Research Triangle Park.
