Professor Sven Danckwardt, MD
Head of Experimental Hemostasis and Laboratory Medicine
The Module Experimental Hemostasis and Laboratory Medicine is mainly concerned with the underlying molecular principles of (de)regulated blood coagulation and the resulting implication for diagnostics and therapy.
In this context the module scientifically focuses on processes of posttranscriptional gene regulation and their role in the regulated (patho)physiology of blood coagulation (and beyond). We dissect gene regulatory mechanisms integrating environmental cues with the aim to understand how these mechanisms might explain previously enigmatic links between deregulated blood coagulation and tumor biology. The other main research focus of the lab is the intricate connection between blood coagulation, inflammation and immunity and how this contributes to various pathophysiologies.
Applying an integrative approach, all scientific topics include elements of basic research (biochemistry, molecular and cellular biology), modeling of diseases in animals and finally understanding the translational implications in patients. Complemented by novel diagnostic tools such as preclinical (molecular) optical imaging, we are aiming to illuminate such processes on a systems level non-invasively in living subjects. Our goal is to integrate this knowledge into novel therapeutic and diagnostic concepts.
We are constantly looking for talented scientists and students. If you are interested in joining our group or you need further information please do not hesitate to contact us.
Important elements of our research are genetically engineered mouse models (GEMMs) as well as non-invasive preclinical optical imaging.
In addition, we develop and apply next generation sequencing based diagnostic tools (sCLIP, TRENDseq, miTRAP) to decipher mechanisms of RNA regulation and to conduct large scale functional RNAi screening analyses. As an example, we recently released TREND-DB an unprecedented "complete" and freely accessible transcriptome database of the APA landscape (aka alternative polyadenylation) of more than 170 knockdown conditions (TREND-DB: explore interactively the dynamic landscape of transcriptome 3'end diversification)
We are part of the DFG Priority Program 1935 - "Deciphering the mRNP code: RNA-bound Determinants of Posttranscriptional Gene Regulation" and the TICARDIO EU Horizon 2020 Research consortium.
Ma, J, Klemm J, Ramírez MG, Frappart, L… Danckwardt S…. Marquardt JU, Hartmann M. CD44 (Cluster of differentiation 44) promotes osteosarcoma progression in mice lacking the tumor suppressor Merlin. Int J Cancer (accepted)
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, Danckwardt S. A novel rationale for targeting FXI: Insights from the hemostastic miRNA targetome for emerging anticoagulant strategies. BioRxiv 2018. https://doi.org/10.1101/501676
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.