@article{KruetznerDroegeKestenetal.2025, author = {Kruetzner, Irina and Droege, Freya and Kesten, Simone and Geisthoff, Urban and Hiepen, Christian}, title = {Disrupted Vessels—Connected Voices: Why Patient Partnership and Cross-Disease Collaboration Are Essential for Accelerating HHT Research}, series = {Biomedicines}, volume = {2025}, journal = {Biomedicines}, number = {13 (12)}, publisher = {MDPI}, issn = {2227-9059}, doi = {10.3390/biomedicines13122997}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1010-opus4-48953}, pages = {8}, year = {2025}, abstract = {Rare vascular diseases such as hereditary haemorrhagic telangiectasia (HHT) represent a big challenge in biomedicine: complex pathomechanisms, limited patient material, and fragmented research communities slow down therapeutic progress. We argue that two elements are pivotal to bypass this problem. First, genuine partnership with patients—ranging from biospecimen donation to agenda setting—can unlock critical resources and align research with real-world needs. Second, molecular intersections between HHT and related pathologies call for coordinated, cross-disease programmes rather than isolated efforts. Recent multi-stakeholder gatherings hosted by patient organisations in Germany and elsewhere, such as the Second Scientific Symposium by the German HHT self-help group (Morbus Osler Selbsthilfe e.V.) in May 2025, have shown that when clinicians, basic scientists from different disciplines, and affected families co-design research questions, novel in vitro models can be generated more accurately, and pragmatic clinical trials emerge. Here, we outline actual opportunities for patient-integrated cellular model systems, shared biobanking, and comparative approaches across vascular malformation syndromes. In our opinion, letting informed and well-organised patient communities assemble such meetings opens unique opportunities twofold: on the one hand, the field can finally break out of its disease-specific silos; on the other hand, the development of novel HHT therapies could be accelerated by learning from progress in related pathologies.}, language = {en} } @article{HiepenBenamarBarrasaFanoetal.2025, author = {Hiepen, Christian and Benamar, Mounir and Barrasa-Fano, Jorge and Condor, Mar and Ilhan, Mustafa and M{\"u}nch, Juliane and Hastar, Nurcan and Kerkhoff, Yannic and Harms, Gregory S. and Mielke, Thorsten and Koenig, Benjamin and Block, Stephan and Rocks, Oliver and Abdelilah-Seyfried, Salim and Van Oosterwyck, Hans and Knaus, Petra}, title = {Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling}, series = {Communications Biology}, journal = {Communications Biology}, number = {8, Article number 21}, publisher = {nature}, doi = {10.1038/s42003-024-07431-8}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1010-opus4-47379}, pages = {1 -- 22}, year = {2025}, abstract = {Abstract Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis.}, language = {en} } @article{HeinksHettwerHiepenetal.2021, author = {Heinks, Tobias and Hettwer, Anette and Hiepen, Christian and Weise, Christoph and Gorka, Marcel and Knaus, Petra and M{\"u}ller, Thomas D. and Loidl-Stahlhofen, Angelika}, title = {Optimized expression and purification of a soluble BMP2 variant based on in-silico design}, series = {Protein Expression and Purification}, volume = {186}, journal = {Protein Expression and Purification}, number = {October}, issn = {1046-5928}, doi = {10.1016/j.pep.2021.105918}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1010-opus4-40229}, pages = {105918}, year = {2021}, abstract = {Bone morphogenetic protein 2 (BMP21) is a highly interesting therapeutic growth factor due to its strong osteogenic/osteoinductive potential. However, its pronounced aggregation tendency renders recombinant and soluble production troublesome and complex. While prokaryotic expression systems can provide BMP2 in large amounts, the typically insoluble protein requires complex denaturation-renaturation procedures with medically hazardous reagents to obtain natively folded homodimeric BMP2. Based on a detailed aggregation analysis of wildtype BMP2, we designed a hydrophilic variant of BMP2 additionally containing an improved heparin binding site (BMP2-2Hep-7M). Consecutive optimization of BMP2-2Hep-7M expression and purification enabled production of soluble dimeric BMP2-2Hep-7M in high yield in E. coli. This was achieved by a) increasing protein hydrophilicity via introducing seven point mutations within aggregation hot spots of wildtype BMP2 and a longer N-terminus resulting in higher affinity for heparin, b) by employing E. coli strain SHuffle® T7, which enables the structurally essential disulfide-bond formation in BMP2 in the cytoplasm, c) by using BMP2 variant characteristic soluble expression conditions and application of L-arginine as solubility enhancer. The BMP2 variant BMP2-2Hep-7M shows strongly attenuated although not completely eliminated aggregation tendency.}, language = {en} }