Professorship for Experimental Hemostasis and Laboratory Medicine

Univ.-Prof. Dr. Sven Danckwardt

We are interested in elucidating gene regulatory processes, the impact of exogenous and endogenous effects on these processes and how this helps to explain complex pathophysiological relationships - such as the enigmatic liaison of blood coagulation and tumor biology. Of particular interest are the mutual interactions of vascular biology, inflammation and immunity.

To address our research questions we persue a translational research approach, which combines tools of basic research (biochemistry, molecular and cell biology), modeling of disease in animals and protein analysis. By utilising state of the art diagnostic tools including preclinical (molecular) optical imaging we visualise these processes non-invasively in live animals. Our aim is to translate our findings into new therapeutic and diagnostic concepts. Examples include RNA therapeutics for regulation of the hemostatic system (Nourse & Danckwardt, Pharmacol Ther 2021; Nourse et al. J Thromb Haemost 2018) and RNA signatures as highly potent novel biomarkers in oncology and other diseases (Ogorodnikov et al. Nature Comm. 2018; Marini et al. Nucleic Acids Res. 2021).

If you are interested in joining our group or need further information please do not hesitate to  contact us.

Research Interests

• Posttranscriptional control in vasculare medicine and beyond
• Role of blood coagulation in tumor biology and beyond (immunology)
• Role of RNA regulation in development and disease (non coding RNAs, miRNAs, RNA binding proteins)

Important elements in our research are genetically modiefied mouse models and non-invasive preclinical optical imaging. Further, we develp and utilise next generation sequenicing (NGS)-based diagnostic techniques (sCLIP, TRENDseq, miTRAP) to decipher mechanisms of RNA regulation and to perform high scale functional RNAi analyses. We generate and publish resources, which support and stimulate translational research activities across disciplines (e.g. TREND-DB: explore interactively the dynamic landscape of transcriptome 3'end diversification).

Partners of Collaboration

Partners at the University Medical Center Mainz

• Prof. Dr. Wolfram Ruf (CTH + The Scripps Research Institute, USA)
• Prof. Dr. Hans Christian Probst (Institut for Immunology)
• Prof. Dr. Tomasso Gori (Center for Cardiology)
• Prof. Dr. Michael Schäfer (Clinic for Anesthesiology)
• Prof. Dr. Wilfried Roth, Mainz (Institut for Pathology)

Nationale Partners

• Prof. Dr. Frank Westermann (DKFZ, Heidelberg)
• Prof. Dr. Stefan Hüttelmaier (Universtiy Medicine Halle)
• Prof. Dr. Ansgar Poetsch (Max-Planck-Institute for Heart and Lung Research, Bad Nauheim + School of Biomedical & Healthcare Sciences, Plymouth University)

International Partners

• Prof. Dr. Pierre Morange (University Aix-Marseille)
• Prof. Dr. Elisabeta Castoldi (CARIM, Maastricht)
• Prof. Dr. Hugo Ten Cate (CARIM, Maastricht)
• Prof. Dr. David-Alexandre Trégouët (University Bordeaux)
• Prof. Dr. Pavel Ivanov (Harvard Medical School, Boston, USA)
• Prof. Dr. Bin Tian (Wistar Institute, Philadelphia, USA)
• Prof. Dr. Wolfram Ruf (CTH + The Scripps Research Institute, USA)
• Prof. Dr. Ansgar Poetsch (Max-Planck-Institute for Heart and Lung Research, Bad Nauheim + School of Biomedical & Healthcare Sciences, Plymouth University)

Biography - Sven Danckwardt

Positions:
Since 2014 – Head of the CTH Platform 'Advanced Diagnostic Platform'
Since 2014 – Scientific Program Director CTH Career Development
Since 2013 – Head of the CTH Platform 'Non-invasive Preclinical Imaging'
Since 2012 – Professor for Experimental Haemostaseology and Laboratory Medicine, CTH, University Medical Center of the Johannes Gutenberg-University, Mainz
2010 - 2011 – Junior Group Leader (Wilhelm-Roux Programm), MLU Munich

Research Career:
2011 – Habilitation, Heidelberg University
2004 - 2011 – Postdoctoral and Senior Physician Scientist, EMBL (European Molecular Biology Laboratory) + MMPU (Molecular Medicine Partnership Unit)
2002 - 2010 – Resident in Haematology, Oncology and Immunology (Pediatrics and Internal Medicine), Charité Berlin and Heidelberg University

Professional Education:
2002 – MD Thesis, Humboldt-University Berlin
1994 - 2001 – Medical Degree, University of Tübingen, Humboldt-University Berlin, San Diego (USA)

Research Funding

• German Research Foundation (DA 1189/2-1 und GRK 1591, University Halle)
• German Research Foundation (INST 371/33-1FUGG)
• Dr. Hella Bühler Award (Cancer Reserach)
• Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL)
• Alexander von Humboldt-Foundation

We are part of the DFG Priority Program 1935 - "Deciphering the mRNP code: RNA-bound Determinants of Posttranscriptional Gene Regulation",the TICARDIO EU Horizon 2020 Research consortium and the IMB International PhD Program.

Team - Module Experimental Hemostasis and Laboratory Medicine

MD Students

• Ludwig Eder, cand. med.
• Lisa Pruschinski, cand. med., DCF Fellow
• Lina Schott, cand. med., DGKL Doktorandenstipendium (ehemalige DCF Fellow)
• Nurten Defne Cetiner, cand. med., DCF Fellow
• Constantia Müller, cand. med., DCF Fellow
• Jonas Niedenthal, cand. med., DCF Fellow
• Maria Elsbernd, cand. med. dent.
• Ann-Celine Mathmann, cand med.
• Sophie Hartleb, cand. med.
• Ranya Al Shekaki, cand. med. 
• Chiara Sauerbier, cand. med.
• Yaman Mouhish, cand. med.

Alumni

• Dr. Lina Schott
• Dr. Michal Levin
• Dr. rer. nat. Shazad Khokhar
• Dr. rer. nat. Anton Ogorodnikov
• Dr. rer. nat. Yulia Kargapolova
• Dr. rer. nat. Sergey Tokalov
• Dr. sc. hum. Kashif Muhammad
• Dr. rer. nat. Kathleen Mühlbach
• Ranya Al Shekaki, MSc
• Svetlana Pavicevic

Selected original articles

• Gogiraju R, Renner L, Bochenek ML, Zifkos K, Molitor M, Danckwardt S, Wenzel P, Münzel T, Konstantinides S, Schäfer K. Arginase-1 Deletion in Erythrocytes Promotes Vascular Calcification via Enhanced GSNOR (S-Nitrosoglutathione Reductase) Expression and NO Signaling in Smooth Muscle Cells. Arterioscler Thromb Vasc Biol. 2022 Dec;42(12):e291-e310
• Nourse J, Tokalov S, Khokhar S, Khan E, Schott LK, Hinz L, Eder L, Arnold-Schild D, Satrapa J,  Lackner KJ, Ten Cate H, Probst HC, Danckwardt S. Non-invasive imaging of gene expression and protein secretion dynamics in living mice: identification of ectopic prothrombin expression as driver of thrombosis in cancer. BioRxiv PrePrint. 2022. doi.org/10.1101/2021.07.08.451623
• Marini F, Scherzinger D, Danckwardt S. TREND-DB-a transcriptome-wide atlas of the dynamic landscape of alternative polyadenylation. Nucleic Acids Res. 2021 Jan 8;49(D1):D243-D253.
• Ma J, Klemm J, Gerardo-Ramírez M, Frappart L, Castven D, Becker D, Zoch A, Parent R, Bartosch B, Minnich K, Giovannini M, Danckwardt S, Hartmann N, Morrison H, Herrlich P, Marquardt JU, Hartmann M. Cluster of differentiation 44 promotes osteosarcoma progression in mice lacking the tumor suppressor Merlin. Int J Cancer. 2020 Nov;147(9) 2564-2577. 
• Schaupp L, Muth S, Rogell L, Kofoed-Branzk M, Melchior F, Lienenklaus S, Ganal-Vonarburg SC, Klein M, Guendel F, Hain T, Schutze K, Grundmann U, Schmitt V, Dorsch M, Spanier J, Larsen PK, Schwanz T, Jäckel S, Reinhardt C, Bopp T, Danckwardt S, Mahnke K, Heinz GA, Mashreghi MF, Durek P, Kalinke U, Kretz O, Huber TB, Weiss S, Wilhelm C, Macpherson AJ, Schild H, Diefenbach A, Probst HC. Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells. Cell 2020;181(5):1080-1096 e1019.
• Häuser F, Gokce S, Werner G, Danckwardt S, Sollfrank S, Neukirch C, Beyer V, Hennermann JB, Lackner KJ, Mengel E, Rossmann H. A non-invasive diagnostic assay for rapid detection and characterization of aberrant mRNA-splicing by nonsense mediated decay inhibition. Mol Genet Metab 2020;130(1):27-35.
• Panova-Noeva M, Wagner B, Nagler M, Arnold N, Prochaska JH, Eckerle S, Spronk HM, Merzenich H, Wingerter A, Schneider A, Danckwardt S, Ten Cate H, Faber J, Wild PS. Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample. Sci Rep 2019;9(1):20090.
• Hain T, Melchior F, Kamenjarin N, Muth S, Weslati H, Clausen BE, Mahnke K, Silva-Vilches C, Schutze K, Sohl J, Radsak MP, Bundgen G, Bopp T, Danckwardt S, Schild H, Probst HC. Dermal CD207-Negative Migratory Dendritic Cells Are Fully Competent to Prime Protective, Skin Homing Cytotoxic T-Lymphocyte Responses. J Invest Dermatol 2019;139(2):422-429.
• Ogorodnikov A, Levin M, Tattikota S, Tokalov S, Hoque M, Scherzinger D, Marini F, Poetsch A, Binder H, Macher-Göppinger S, Probst HC, Tian B, Schaefer M, Lackner KJ, Westermann F, Danckwardt S. Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma. Nat Commun 2018;9(1):5331.
• Nourse J, Braun J, Lackner K, Huttelmaier S, Danckwardt S. Large-scale identification of functional microRNA targeting reveals cooperative regulation of the hemostatic system. J Thromb Haemost 2018;16(11):2233-2245.
• Kargapolova Y, Levin M, Lackner K, Danckwardt S (2017) sCLIP-an integrated platform to study RNA-protein interactomes in biomedical research: identification of CSTF2tau in alternative processing of small nuclear RNAs. Nucleic Acids Res 2017;45(10):6074-6086.
• Steven S, Jurk K, Kopp M, Kröller-Schön S, Mikhed Y, Schwierczek K, Roohani S, Kashani F, Oelze M, Klein T, Tokalov S, Danckwardt S, Strand S, Wenzel P, Münzel T, Daiber A. (2016). Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice. Br J Pharmacol. 2017;174(12):1620-1632.
• Danckwardt S, Gantzert AS, Macher-Goeppinger S, Probst HC, Gentzel M, Wilm M et al. p38 MAPK Controls Prothrombin Expression by Regulated RNA 3' End Processing. Mol Cell. 41(3):298-310, 2011.
• Danckwardt S, Kaufmann I, Gentzel M, Foerstner KU, Gantzert AS, Gehring NH, Neu-Yilik G, Bork P, Keller W, Wilm M, Hentze MW, Kulozik AE. Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals. The EMBO journal. 26:2658-2669, 2007.
• Danckwardt S, Hartmann K, Katz B, Hentze MW, Levy Y, Eichele R, Deutsch V, Kulozik AE, Ben-Tal O.The prothrombin 20209 C-->T mutation in Jewish-Moroccan Caucasians: molecular analysis of gain-of-function of 3' end processing. J Thromb Haemost. 4(5):1078-85, 2006.
• Danckwardt S, Gehring NH, Neu-Yilik G, Hundsdoerfer P, Pforsich M, Frede U, Hentze MW, Kulozik AE.The prothrombin 3'end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations. Blood. 104(2):428-35, 2004.
• Danckwardt S, Neu-Yilik G, Thermann R, Frede U, Hentze MW, Kulozik AE. Abnormally spliced beta-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay. Blood. 99:1811-1816, 2002.

Reviews

• Danckwardt S, Trégouët DA, Castoldi E. Post-transcriptional control of hemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders. Cardiovasc Res. 2023 Mar 21:cvad046
• Spada S, Luke B, Danckwardt S. The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen. Front Gen. 2022 Apr
• Ogorodnikov A, Danckwardt S. TRENDseq—A highly multiplexed high throughput RNA 3′ end sequencing for mapping alternative polyadenylation. Methods Enzymol. 2021;655:37-72.
• Nourse J, Danckwardt S. A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies. Pharmacol Ther. 2021 Feb;218:107676.
• Nourse J, Spada S, Danckwardt S. Emerging Roles of RNA 3'-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders. Biomolecules. 2020 Jun 17;10(6):915.
• Ogorodnikov, A, Kargapolova Y, Danckwardt S. Processing and transcriptome expansion at the mRNA 3' end in health and disease: finding the right end. Pflugers Arch 468(6): 993-1012.
• Krenzlin H, Lorenz V, Danckwardt S, Kempski O, Alessandri B. The Importance of Thrombin in Cerebral Injury and Disease. Int J Mol Sci. 2016 Jan 11;17(1):84.
• Danckwardt S, Hentze MW, Kulozik AE. Pathologies at the nexus of blood coagulation and inflammation: Thrombin in Hemostasis, Cancer and beyond. J Mol Med. 91(11):1257-71.
• Danckwardt S, Hentze MW, Kulozik AE.3' end mRNA processing: molecular mechanisms and implications for health and disease. EMBO J. 6;27(3):482-98, 2008.
• Danckwardt S, Hartmann K, Gehring NH, Hentze MW, Kulozik AE. 3' end processing of the prothrombin mRNA in thrombophilia. Acta Haematol. 115(3-4):192-7, 2006.

TREND-DB: explore interactively the dynamic landscape of transcriptome 3'end diversification (TREND)