About

Wolfgang Bergmeier, PhD, is a Professor of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill. He serves as the Director of Graduate Studies and is a member of the Green Labs Sustainability Committee within the Department of Biochemistry and Biophysics. Dr. Bergmeier is affiliated with the UNC Blood Research Center, where his laboratory fosters a diverse and welcoming environment aimed at addressing challenging scientific problems through creative and novel solutions. His professional contact information includes an office and lab phone number, and he is based in the Mary Ellen Jones Building at UNC Chapel Hill. The Bergmeier Lab emphasizes the importance of diverse viewpoints to enhance both research and community, reflecting Dr. Bergmeier's commitment to excellence in scientific inquiry and education.

Research topics

• Internal medicine
• Medicine
• Immunology
• Intensive care medicine
• Chemistry
• Biology
• Biochemistry
• Cardiology
• Molecular biology
• Gastroenterology
• Andrology
• Pathology
• Pharmacology
• Bioinformatics
• Surgery
• Cell biology
• Endocrinology

Selected publications

• A Novel G13-RAPGEF2-RAP1 Signaling Pathway Critical for Platelet Adhesion

  Blood · 2026-04-08

  articleOpen accessSenior author

  Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1-/-), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared to control or Caldaggef1-/- platelets, both RAP1 activation and integrin aIIbb3-mediated aggregation were significantly diminished in DKO platelets. When compared to controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein, G13 (GNA13), such as aIIbb3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease.

  PublisherDOI

• Data Management and Sharing Plan for: Novel pathways and mechanisms underlying disorders of platelet count and/or function

  UNC Dataverse · 2026-01-01

  datasetOpen access1st authorCorresponding

  The Data Management and Sharing Plan describes the scientific data to be generated and/or used in the research and outlines a strategy for managing and sharing project data.

  PublisherDOI

• Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation

  Circulation Research · 2025-07-01 · 9 citations

  article

  BACKGROUND: Platelet activation relies on changes in cytoplasmic calcium flux. However, little is known about the role mitochondrial calcium flux plays in platelet activation. Activation induces release of calcium from intracellular stores, which enters the mitochondrial matrix through the MCU (mitochondrial calcium uniporter) to regulate bioenergetics and reactive oxygen species (ROS) formation, as demonstrated in other cells. However, whether MCU contributes to platelet function is unclear. METHODS: We generated platelet-specific Mcu-deficient mice ( Mcu plt −/− ) and compared them to littermate wild-type controls ( Mcu plt+/+ ). In vitro approaches assessed mitochondrial calcium flux and platelet activation responses to stimulation of immunoreceptor tyrosine-based activation motif (ITAM) receptors and GPCRs (G protein–coupled receptors). In addition, we examined in vivo hemostasis and thrombosis. We also treated human platelets with MCU inhibitors, and platelet function was assessed. RESULTS: Mcu plt −/ − platelets had significantly reduced mitochondrial calcium flux in response to activation of ITAM receptors, whereas mitochondrial calcium flux in response to GPCR activation was unchanged. Platelet aggregation was significantly reduced by ITAM activation in Mcu plt −/ − platelets, but GPCR-induced aggregation was unchanged. Similar findings were observed when MCU was inhibited in human platelets. In vivo, Mcu plt −/ − mice had reduced arterial thrombosis and less ischemic stroke brain injury. Hemostasis was mildly altered in Mcu plt −/ − mice. Mechanistically, mitochondrial ROS generation was significantly reduced in Mcu plt −/ − platelets compared with Mcu plt+/+ platelets after ITAM-dependent activation, but not GPCR activation. Reduced mitochondrial ROS was associated with decreased ITAM signaling based on p-Syk (phospho–spleen tyrosine kinase) and p-PLCγ2 (phospho–phospholipase C-gamma 2) in Mcu plt −/ − platelets. Inhibiting mitochondrial ROS decreased aggregation as well as downstream ITAM signaling in Mcu plt+/+ platelets. Conversely, treating Mcu plt −/ − platelets with MitoParaquat to induce mitochondrial ROS increased platelet ITAM-dependent aggregation and signaling. CONCLUSIONS: Our data support a role for mitochondrial calcium flux in regulating ITAM-dependent platelet activation through the generation of mitochondrial ROS.

  PublisherDOI

• Platelet-mediated activation of perivascular mast cells triggers progression of sepsis to septic shock in mice

  UNC Libraries · 2025-12-11

  articleOpen access
  PublisherDOI

• HTRS2025.P1.46 Evaluation of bleeding and platelet dysfunction in a mouse model of vascular Ehlers Danlos syndrome

  Research and Practice in Thrombosis and Haemostasis · 2025-11-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Platelet-mediated activation of perivascular mast cells triggers progression of sepsis to septic shock in mice

  Nature Communications · 2025-12-03 · 2 citations

  articleOpen access

  The critical events that trigger sepsis progression into life-threatening septic shock remain unclear. In agreement with reports that link a drop in platelet count to a complicated clinical course in sepsis patients, here we report that, during sepsis, mouse platelets become activated, deposit systemically on vascular walls, and stimulate perivascular mast cells (MC) by releasing platelet activating factor (PAF). In mouse models and patient samples, MC activation correlates with the development of shock in sepsis and is mechanistically linked to shock by inducing systemic hypotension, vascular leakage and microvascular perfusion abnormalities. Preventing platelet or MC activation, or inhibiting the activity of the major MC granule constituent chymase, averts progression from sepsis to shock and reduces mortality of septic mice. Thus, our work establishes that, during sepsis progression, platelet microvascular adhesion leads to MC-mediated vascular changes to culminate in septic shock and septic shock-associated mortality. Sepsis may progress into lethal septic shock, but the cellular mechanisms are still unclear. Here the authors show that, in septic mice, platelets activate perivascular mast cells to cause systemic hypotension and vascular pathology, while inhibiting platelets or mast cell activation suppresses septic shock induction, thereby implicating potential therapy targets.

  PublisherOA PDFDOI

• Modeling platelet P2Y1/12 pathway to integrin activation

  Biophysical Journal · 2025-04-08 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Lack of overt bleeding or platelet dysfunction in a mouse model of vascular Ehlers–Danlos syndrome

  Journal of Thrombosis and Haemostasis · 2025-05-17

  letterSenior author
  PublisherDOI

• Loss of P2Y1 receptor desensitization does not impact hemostasis or thrombosis despite increased platelet reactivity in vitro

  UNC Libraries · 2025-09-27

  articleOpen access
  PublisherDOI

• GTPases

  2025-01-01

  book-chapterSenior author
  PublisherDOI

Recent grants

• NIH Grant R01HL106009

  NIH · $1.5M · 2016

• NIH Grant R01HL094594

  NIH · $1.9M · 2014

• Rap1 signaling in platelet homeostasis and vascular hemostasis

  NIH · $1.2M · 2016–2020

• Small GTPases in megakaryocyte biology

  NIH · $1.8M · 2017–2021

• Spatial regulation of platelet activation by Podoplanin-Clec2 signaling

  NIH · $1.2M · 2014–2018

Frequent coauthors

• Yacine Boulaftali

  Université Paris Cité

  66 shared

• David S. Paul

  University of North Carolina at Chapel Hill

  57 shared

• Lucia Stefanini

  Sapienza University of Rome

  56 shared

• Robert H. Lee

  50 shared

• Moritz Stolla

  Bloodworks Northwest

  49 shared

• Nigel Mackman

  47 shared

• Paul F. Bray

  University of Utah

  47 shared

• Firdos Ahmad

  University of Sharjah

  41 shared

Labs

• The Bergmeier LabPI

Awards & honors

• Outstanding Investigator Award, National Heart, Lung and Blo…
• Chair of 9th Symposium of Hemostasis, Chapel Hill, North Car…
• Vice Chair of the Gordon Research Conference on the Cell Bio…
• American Heart Association, ATVB Special Recognition Award i…
• American Association of Clinical Chemistry, 2015