Two zebrafish embryos showing the migration of endothelial cells (green).
Friedrich Kapp, MD
Clinical Head of Vascular Anomalies
T: +49 (0)761 270-45203
F: +49 (0)761 270-43366
Department of Pediatric Hematology and Oncology
Center for Pediatrics and Adolescent Medicine
The impact of novel mutations found in next generation sequencing is often unknown in vascular malformations as well as in other diseases. To enhance our understanding of the genetic framework of vascular anomalies, we model these diseases in the zebrafish embryo. This allows us to study aberrant cellular processes during the development of vascular anomalies and to identify causative mutations in patients, which hopefully will help to direct treatment in the future.
- Cora Beckmann, MD student: Modelling novel mutations in hematopoietic diseases
- Lorenz Bell, MD student: Modelling novel mutations in vascular malformations
- Anna Hermann, MD student, and Cedric Schneider, dentistry student: Clinical research on rare vascular malformations
- Angelina Meier, technician
The genetic basis of vascular anomalies is only beginning to be understood via the identification of recurrent mutated genes. RAS-pathway mutations are often found in high-flow (arterio-venous) malformations, while low-flow malformations (venous and lymphatic malformations) are often caused by aberrations in the PIK3CA/mTOR-pathway. However, the downstream consequences of the mutations, the epigenetic changes and the abnormal processes leading to the development of vascular malformations remain largely unknown. This lack of knowledge hinders the development of novel, targeted therapeutics.
We have developed a pipeline with which we can rapidly assess the effect on the hematopoietic system of mutations found in patients. This allows us to identify causative mutations in blood diseases and to test selected drugs in the context of these diseases.
We recently expanded this pipeline to zebrafish. This will allow us to identify novel causative mutations and to establish faithful disease models for vascular malformations to study and understand these rare diseases in more detail.
EXCEL-Fellowship (sponsored by the Else-Kröner-Fresenius Foundation)
Faculty of Medicine, University of Freiburg
- Kapp FG, Perlin JR, Hagedorn EJ, Gansner JM, Schwarz DE, O’Connell LA, Johnson NS, Amemiya C, Fisher DE, Wölfle U, Trompouki E, Niemeyer CM, Driever W, Zon LI. Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 2018 558, 445–448. https://doi.org/10.1038/s41586-018-0213-0
- Piragyte I, Clapes T, Klein-Geltnik R, Yin N, Polyzou A, Langa Oliva X, Beckmann C, Lefkopoulos S , Theißen P, Wlodarski M, Van Essen D, Rambold A, Kapp FG, Mione M, Pearce E, Polyzos A, Trompouki E. A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways. Nature Communications 2018 9, 3090. https://doi.org/10.1038/s41467-018-05311-4
- Patsch C, Challet-Meylan L, Thoma EC, Urich E., Heckel T, O’Sullivan, JF, Grainger SJ, Kapp, FG, Sun L, Christensen K, Xia Y, Florido MHC, He W, Pan W, Prummer M, Warren CR, Jakob-Roetne R, Certa U, Jagasia R, Freskgård PO, Adatto I, Kling D, Huang P, Zon LI, Chaikof EL, Gerszten RE, Graf M, Iacone R, Cowan CA. Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nature Cell Biology 2015 Aug;17(8):994-1003. https://doi.org/10.1038/ncb3205
- Kapp FG, Sommer A, Kiefer T, Dolken G, Haendler B. 5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis. Cancer Cell International 2012 Jan;12(1):1. https://doi.org/10.1186/1475-2867-12-1
- Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). Journal of Medical Toxicology 2011 Sept;7(3), 227–231. https://doi.org/10.1007/s13181-011-0155-5