Deutsch Intern
Rudolf Virchow Center for Integrative and Translational Bioimaging

Stegner Group

About the Stegner Group

Thrombo-inflammatory diseases, such as ischemic stroke, are major causes of death and disability worldwide.

Our research focuses on the mechanisms of thrombo-inflammation and the interaction between platelets and immune cells in various diseases such as stroke or liver inflammation. To do so we capitalize on advanced fluorescence microscopy techniques and transgenic mouse models to study the role of platelets in inflammatory processes.

The term thrombo-inflammation was used first to describe the interplay of components of the thrombotic and inflammatory system driving ischemia/reperfusion (I/R) injury in acute ischemic stroke. Today, thrombo-inflammation is recognized as a major pathomechanism in a continuously growing number of disorders in different organs and disease states. Despite platelets being critically involved, the classical thrombosis is not the major pathophysiological event leading to organ damage, which discriminates thrombo-inflammation from immunothrombosis.

For many thrombo-inflammatory diseases the underlying mechanisms are largely unknown and therapeutic options are limited. To develop novel treatment strategies, it is necessary to understand the detrimental interplay between thrombotic and inflammatory circuits, which would only be possible if the cellular interactions can be visualized. To image thrombo-inflammatory processes and their consequences with different advanced imaging modalities, we collaborate intensively with the Bio-Imaging Center. By developing new tools and protocols for visualizing platelets and their precursor cells, megakaryocytes (MKs), using multiphoton intra-vital microscopy (2P-IVM) and light-sheet fluorescence microscopy, we have challenged previous concepts of MK maturation and clarified their interaction with neutrophils in the bone marrow. With the established techniques we currently aim to study and visualize alterations in the bone marrow upon thrombo-inflammation in the context of myocardial infarction. So far, our findings provided new insights into the pathomechanisms underlying ischaemic stroke and identify key factors involved in infarct progression, such as the neuronal capacitive calcium channel Orai2, platelet degranulation, and the platelet receptor CD84. Additionally, we have discovered a CLEC-2/αIIbβ3-dependent platelet activation pathway as a powerful trigger of cerebral venous thrombosis (CVT) in mice, offering the first direct evidence for aberrant platelet activation as a major trigger of CVT and a potential target for treatment.

Navarro S, Vögtle T, Groß N, Preu J, Englert M, Nieswandt B, Bösl MR*, Stegner D*. Mutations of the dimerization site of glycoprotein (GP) VI result in abolished expression. Thromb Res 2023. DOI: 10.1016/j.thromres.2023.10.016


Karwen T, Kolczynska-Matysiak K, Gross C, Löffler MC, Friedrich M, Loza-Valdes A, Schmitz W, Wit M, Dziaczkowski F, Belykh A, Trujillo-Viera J, El-Merahbi R, Deppermann C, Nawaz S, Hastoy B, Demczuk A, Erk M, Wieckowski MR, Rorsman P, Heinze KG, Stegner D*, Nieswandt B*, Sumara G*. Platelet-derived lipids promote insulin secretion of pancreatic β cells. EMBO Mol Med. 2023;15:e16858. DOI: 10.15252/emmm.202216858..


Beck S, Öftering P, Li R, Hemmen K, Nagy M, Wang Y, Zarpellon A, Schuhmann MK, Stoll G, Ruggeri ZM, Heinze KG, Heemskerk JWM, Ruf W*, Stegner D*, Nieswandt B*. Platelet glycoprotein V spatio-temporally controls fibrin formation. Nat Cardiovasc Res. 2023;2:368-382. DOI: 10.1038/s44161-023-00254-6.


Brown HC, Beck S, Navarro S, Di Y, Soriano Jerez EM, Kaczmarzyk J, Thomas SG, Mirakaj V, Watson SP, Nieswandt B, Stegner D. Antibody-mediated depletion of human CLEC-2 in a novel humanised mouse model. Blood Adv. 2022;7:997-1000. DOI: 10.1182/bloodadvances.2021006463.


Schuhmann MK, Stoll G, Bieber M, Vögtle T, Hofmann S, Klaus V, Kraft P, Seyhan M, Kollikowski AM, Papp L, Heuschmann PU, Pham M, Nieswandt B, Stegner D. CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke. Circ Res. 2020;127:1023-35.


Stegner D, Göb V, Krenzlin V, Beck S, Hemmen K, Schuhmann MK, Schörg BF, Hackenbroch C, May F, Burkard P, Pinnecker J, Zernecke A, Rosenberger P, Greinacher A, Pichler BJ, Heinze KG, Stoll G, Nieswandt B. Foudroyant cerebral venous (sinus) thrombosis triggered through CLEC-2 and GPIIb/IIIa dependent platelet activation. Nat Cardiovasc Res. 2022;1:132-141. DOI: 10.1038/s44161-021-00017-1.


Göb V, Voll MG, Zimmermann L, Hemmen K, Stoll G, Nieswandt B, Schuhmann MK, Heinze KG, Stegner D. Infarct growth precedes cerebral thrombosis following experimental stroke in mice. Sci Rep. 2021;11:22887. DOI: 10.1038/s41598-021-02360-6.


Schuhmann MK, Stoll G, Bieber M, Vögtle T, Hofmann S, Klaus V, Kraft P, Seyhan M, Kollikowski AM, Papp L, Heuschmann PU, Pham M, Nieswandt B, Stegner D. CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke. Circ Res. 2020; 127(8):1023-1035. DOI: 10.1161/CIRCRESAHA.120.316655.


Stegner D, Hofmann S, Schuhmann MK, Kraft P, Herrmann AM, Popp S, Höhn M, Popp M, Klaus V, Post A, Kleinschnitz C, Braun A, Meuth SG, Lesch KP, Stoll G, Kraft R, Nieswandt B. Loss of Orai2-Mediated Capacitative Ca2+ Entry Is Neuroprotective in Acute Ischemic Stroke. Stroke. 2019;50:3238-45. DOI: 10.1161/STROKEAHA.119.025357.


Stegner D, van Eeuwijk JMM, Angay O, Gorelashvili MG, Semeniak D, Pinnecker J, Schmithausen P, Meyer I, Friedrich M, Dütting S, Brede C, Beilhack A, Schulze H, Nieswandt B, Heinze KG. Thrombopoiesis is spatially regulated by the bone marrow vasculature. Nat Commun. 2017; 8:127. DOI: 10.1038/s41467-017-00201-7.


Stegner D, Popp M, Lorenz V, Wax JK, Gessner JE, Nieswandt B. FcγRIIB on liver sinusoidal endothelial cells is essential for antibody-induced GPVI ectodomain shedding in mice. Blood. 2016; 128:862-5. DOI: 10.1182/blood-2016-05-714378.

Vanessa Göb

Postdoc
Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: D15
Room: 02.011

Juliana Goldmann

Technische/r Assistent/in
Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: D15
Room: 02.103

Ewa Stepien-Bötsch

Technische/r Assistent/in
Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 02.103

Christian Hackenbroch

Doktorand/in
Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: D15
Room: 02.011
Phone: 093131-99814

Sahana Anantharamu

Doktorand/in (SFB1525-A07)
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 02.011

Lexiao Li

Postdoc
Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging
Universität Würzburg
Josef-Schneider-Straße 2
97080 Würzburg
Deutschland
Building: Haus D15

Current position

W2 Professor of Vascular Imaging

Research Experience

since 2021   W2 Professor of Vascular Imaging at the Rudolf Virchow Center
since 2018 Scientific secretary of the collaborative research center SFB/TR 240 and and project leader in the SFB/TR 240 (TP B06 and B08)
2016 – 2021 Junior Group Leader Vascular Imaging at the Institute for Experimental Biomedicine of the University Hospital Würzburg
2016 – 2017 Scientific secretary of the collaborative research center SFB 688
2014 – 2016 Postdoctoral Fellow at the Rudolf Virchow Center of the University of Würzburg with Prof. B. Nies­wandt
2014 – 2017 Project leader within the collaborative research center 688 (SFB 688 – TP B07)
2012 – 2013 Postdoctoral Fellow at the Department of Neurology of the University Hospital Würzburg with Prof. G. Stoll
2011 – 2012                             Postdoctoral Fellow at the Department of Experimental Biomedicine at the University Hospital Würzburg with Prof. B. Nieswandt

Education

2011                   PhD (Dr. rer. nat.) in Experimental Biomedicine, University of Würzburg
2006 Diploma in biochemistry at the University of Bayreuth

 

Awards and scholarships

2015, 2014, 2013       Young Investigator Award of the International Society of Thrombosis and Haemostasis (ISTH)
2007 - 2011

Doctoral Fellowship of the Graduate School of Life Sciences, University of Würzburg