1997 - 2006: High school, Bonn, Germany
2007 - 2008: Police officer training, Hahn, Germany
2008 - 2015: Medical training, Heidelberg, Germany
2015 - 2016: Resident in General Surgery, Eschweiler, Germany
2016: Resident in Internal Medicine, Aachen, Germany
Doctor of Medicine, Ruprecht Karl Universitat Heidelberg (2015)
Gerlinde Wernig, Postdoctoral Faculty Sponsor
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures.
Stem cell reports
Osteoporosis and osteoporotic fractures lead to decreased life quality and high healthcare costs. Current treatments prevent losses in bone mass and fractures to some extent but have side effects. Therefore, better therapies are needed. This study investigated whether the transcriptionfactor Jun has a specific pro-osteogenic potency and whether modulating Jun could serve as a novel treatment for osteoporosis-associated fractures. We demonstrate that ectopically transplanted whole bones and distinct osteoprogenitors increase bone formation. Perinatal Jun induction disturbs growth plate architecture, causing a striking phenotype with shortened and thickened bones. Molecularly, Jun induces hedgehog signaling in skeletal stem cells. Therapeutically, Jun accelerates bone growth and healing in a drilling-defect model. Altogether, these results demonstrate that Jun drives bone formation by expanding osteoprogenitor populations and forcing them into the bone fate, providing a rationale for future clinical applications.
View details for DOI 10.1016/j.stemcr.2020.02.009
View details for PubMedID 32197115
Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity.
2020; 11 (1): 2795
The transcription factor JUN is highly expressed in pulmonary fibrosis. Its induction in mice drives lung fibrosis, which is abrogated by administration of anti-CD47. Here, we use high-dimensional mass cytometry to profile protein expression and secretome of cells from patients with pulmonary fibrosis. We show that JUN is activated in fibrotic fibroblasts that expressed increased CD47 and PD-L1. Using ATAC-seq and ChIP-seq, we found that activation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We further detect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. Using an in vivo mouse model of fibrosis, we found two distinct mechanisms by which blocking IL-6, CD47 and PD-L1 reversed fibrosis, by increasing phagocytosis of profibrotic fibroblasts and by eliminating suppressive effects on adaptive immunity. Our results identify specific immune mechanisms that promote fibrosis and suggest a therapeutic approach that could be used alongside conventional anti-fibrotics for pulmonary fibrosis.
View details for DOI 10.1038/s41467-020-16466-4
View details for PubMedID 32493933