Wolfgang Bergmeier, PhD

Bergmeier_Wolfgang

Associate Professor of Biochemistry and Biophysics

PHD - Witten/Herdecke University  

HONORS & AWARDS

  • Established Investigator Award, American Heart Association - 2013
  • Investigator Recognition Award (BACH), International Society on Thrombosis & Haemostasis - 2013
  • Junior Faculty Scholar Award, American Society of Hematology - 2009
  • Kenneth M. Brinkhous Young Investigator Prize in Thrombosis, American Heart Association - 2009

RESEARCH

Our research focuses on the adhesion mechanisms of platelets and neutrophils to sites of vascular injury/ activation. For successful adhesion, both cell types rely on activation-dependent receptors (integrins) expressed on the cell surface. We are particularly interested in the role of calcium (Ca2+) as a signaling molecule that regulates the inside-out activation of integrin receptors.

Current research efforts are focused in three major areas:

1. Signaling events downstream of Ca2+

In recent studies, we were the first to identify CalDAG-GEFI as a signaling molecule critical to Ca2+-dependent integrin activation in platelets and neutrophils. Our studies further demonstrated that CalDAG-GEFI synergizes with protein kinase C (PKC) in the regulation of various aspects of platelet activation, including integrin activation and the generation of autocrine agonists such as thromboxane A2 and ADP. Consequently, mice lacking CalDAG-GEFI were characterized by a markedly impaired hemostatic and inflammatory response. We use various molecular, biochemical, and cellular strategies to better understand how CalDAG-GEFI function is regulated by Ca2+ and how it links Ca2+ to a range of responses triggered by cellular activation. We are currently also screening for small molecule inhibitors that could be used to interfere with CalDAG-GEFI function in the clinical settings of thrombosis and inflammation.

2. Molecules regulating Ca2+ influx in platelets and neutrophils

The intracellular Ca2+ concentration of many non-excitable cells is regulated by Ca2+ store release and store-operated Ca2+ entry (SOCE). We and others have recently identified STIM1 and Orai1 as critical regulators of SOCE in platelets. While STIM1 serves as a Ca2+ sensor in the endo-/sarco-plasmatic reticulum, Orai1 is the major Ca2+ channel expressed in the plasma membrane. In future studies, we hope to better understand how impaired STIM1/Orai1 function affects platelet function, especially with regard to responses regulated by CalDAG-GEFI.

3. Calcium signaling and ischemia-reperfusion injury

Myocardial Infarction (MI) and Deep Vein Thrombosis (DVT) are a national health concern, with over a million deaths per year. Reperfusion-induced tissue injury is a driving force of ischemic diseases such as MI and DVT. An important role for both leukocytes and platelets in the development of reperfusion injury has been described. We will evaluate how impaired Ca2+ signaling (CalDAG-GEFI, STIM1, Orai1) in platelets and/or neutrophils affects tissue damage in mouse models of reperfusion injury.

RECENT PUBLICATIONS  pubmed.png (click for Full Publication List)

  • Boulaftali Y, Hess PR, Getz TM, Cholka A, Stolla M, Mackman N, Owens III AP, Ware J, Kahn ML, Bergmeier W. Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest.  2013 Feb 1;123(2):908-16. 
  • Stefanini L, Boulaftali Y, Ouellette TD, Holinstat M, Désiré L, Leblond B, Andre P, Conley PB, Bergmeier W. Rap1-Rac1 Circuits Potentiate Platelet Activation. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):434-41.    
  • Stolla M, Stefanini L, André P, Ouellette TD, Reilly MP, McKenzie SE, Bergmeier W. CalDAG-GEFI deficiency protects mice in a novel model of FcγRIIA-mediated thrombosis and thrombocytopenia. Blood. 2011 Jul 28;118(4):1113-20
  • Ahmad F, Boulaftali Y, Greene TK, Ouellette TD, Poncz M, Feske S, Bergmeier W. Relative Contribution of STIM1 and CalDAG-GEFI to Calcium-Dependent Platelet Activation and Thrombosis. J Thromb Haemost. 2011 Oct;9(10):2077-86  
  • Stolla M, Stefanini L, André P, Ouellette TD, Reilly MP, McKenzie SE, Bergmeier W. CalDAG-GEFI deficiency protects mice in a novel model of Fc{gamma}RIIA-mediated thrombosis and thrombocytopenia. Blood. 2011 Jul 28;118(4):1113-20.   
  • Stolla M, Stefanini L, Roden RC, Chavez M, Hirsch J, Greene T, Ouellette TD, Maloney SF, Diamond SL, Poncz M, Woulfe DS, Bergmeier W. The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: Implications for antiplatelet therapy. Blood, 117(3):1005-13, 2011.
  • Stefanini L, Roden RC, Bergmeier W. CalDAG-GEFI is at the Nexus of Calcium-dependent Platelet Activation. Blood. Sep 17,114(12):2506-14, 2009.
  • Bergmeier W, Oh-Hora M, McCarl CA, Roden RC, Bray PF, Feske S. R93W mutation in Orai1 causes impaired calcium influx in platelets. Blood. 113(3):675-8, 2009.
  • Cifuni SM, Wagner DD, Bergmeier W. CalDAG-GEFI And Protein Kinase C (PKC) Represent Alternative Pathways Leading To Activation Of Integrin aIIbb3 In Platelets. Blood. 112(5):1696-703, 2008.
  • Bergmeier W, Goerge T, Wang HW, Crittenden JR, Baldwin ACW, Cifuni SM, Housman DE, Graybiel AM, Wagner DD. Mice lacking the signaling molecule, CalDAG-GEFI, represent a model for leukocyte adhesion deficiency type III. J Clin Invest. 117(6):1699-707, 2007.
  • Bergmeier W, Piffath CL, Goerge T, Cifuni SM, Ruggeri ZM, Ware J, Wagner DD. The role of platelet adhesion receptor GPIb{alpha} far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A. 103(45):16900-16905, 2006.
  • Crittenden JR*, Bergmeier W*, Zhang Y, Piffath CL, Liang Y, Wagner DD, Housman DE, Graybiel AM. Calcium and diacylglycerol signaling through CalDAG-GEFI controls platelet aggregation. Nat Med. 10(9):982-6, 2004.
  • Bergmeier W, Piffath CL, Cheng G, Dole VS, Zhang Y, von Andrian UH, Wagner DD. Tumor Necrosis Factor-a-Converting Enzyme (ADAM17) Mediates GPIba Shedding from Platelets In Vitro and In Vivo.  Circ Res. 95(7):677-83, 2004.
  • Hoffmeister KM, Felbinger TW, Falet H, Denis CV, Bergmeier W, Mayadas TN, von Andrian UH, Wagner DD, Stossel TP, Hartwig JH. The clearance mechanism of chilled blood platelets. Cell. 112:87-97, 2003.
  • Bergmeier W, Burger PC, Piffath CL, Hoffmeister KM, Hartwig JH, Nieswandt B, Wagner DD.  Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood. 102: 4229-4235, 2003.

CONTACT INFORMATION

Bergmeier Lab Website

98 Manning Drive
Campus Box # 7035
306A M.E. Jones Bldg
Chapel Hill, NC 27599

Office: 919-962-7331
Fax: 919.966.7639
bergmeie@email.unc.edu

Lab Rooms: 306 & 308
Mary Ellen Jones Bldg

Lab Phone: 919-962-7332