Prof. Dr. Alexander Zarbock
"No positions via CiM-IMPRS in 2024"
Molecular mechanisms of integrin activation and leukocyte recruitment
Cell Biology / Molecular Biology
Imaging Technology
Immunology
Precise targeting of leukocytes to their marked battlegrounds is a key strategy for victory by the immune defense. Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. Different sequential recruitment steps have been identified that each necessitates distinct functioning of particular members of the integrin family of adhesion molecules. We focus on unraveling the mechanisms behind integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration. Each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. We use genetic approaches along with cell biological and imaging techniques to identify new molecules and mechanisms. Further insights into these signaling pathways may allow providing new approaches for the development of the next generation of anti-inflammatory drugs.
Vita
- 1996 - 2003: Studies in Medicine, Düsseldorf
- 2003 - 2005: Postdoc, Department of Anesthesiology and Critical Care, University of Münster
- 2005 - 2007: Postdoc, Cardiovascular Research Center (Prof. Ley), University of Virginia, USA
- 2007 - 2008: Postdoc, La Jolla Institute for Allergy and immunology, CA, USA
- 2008 - 2015: Postdoc, (since 2010: Assistant Professor) Department of Anesthesiology and Critical Care, University of Muenster and Group leader (Emmy-Noether Nachwuchsgruppe, DFG) at the Max-Planck Institute for Molecular Biomedicine, Muenster
- 2010: Habilitation
- 2012: Heisenberg Professor
- Since 2016: Director of the Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster
Selected references
Rossaint J, Kühne K, Skupski J, Van Aken H, Looney MR, Hidalgo A, Zarbock A (2016). Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun 2016 Nov 15;7:13464
Rossaint J, Oehmichen J, Van Aken H, Reuter S, Pavenstädt HJ, Meersch M, Unruh M, Zarbock A (2016). FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest 126(3):962-74.
Volmering S, Block H, Boras M, Lowell CA, Zarbock A (2016). The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation. Immunity. 44(1):73-87.
Block H, Stadtmann A, Riad D, Rossaint J, Sohlbach C, Germena G, Wu D, Simon SI, Ley K, Zarbock A (2016). Gnb isoforms control a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo. Blood 127(3):314-24.
Stadtmann A, Block H, Volmering S, Abram C, Sohlbach C, Boras M, Lowell CA, Zarbock A (2015). Cross-Talk between Shp1 and PIPKIγ Controls Leukocyte Recruitment. J Immunol. 195(3):1152-61.
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