Bio

Bio


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

Professional Education


  • Doctor of Medicine, Ruprecht Karl Universitat Heidelberg (2015)

Stanford Advisors


Publications

All Publications


  • CD47 prevents the elimination of diseased fibroblasts in scleroderma. JCI insight Lerbs, T., Cui, L., King, M. E., Chai, T., Muscat, C., Chung, L., Brown, R., Rieger, K., Shibata, T., Wernig, G. 2020; 5 (16)

    Abstract

    Scleroderma is a devastating fibrotic autoimmune disease. Current treatments are partly effective in preventing disease progression but do not remove fibrotic tissue. Here, we evaluated whether scleroderma fibroblasts take advantage of the "don't-eat-me-signal" CD47 and whether blocking CD47 enables the body's immune system to get rid of diseased fibroblasts. To test this approach, we used a Jun-inducible scleroderma model. We first demonstrated in patient samples that scleroderma upregulated transcription factor JUN and increased promoter accessibilities of both JUN and CD47. Next, we established our scleroderma model, demonstrating that Jun mediated skin fibrosis through the hedgehog-dependent expansion of CD26+Sca1- fibroblasts in mice. In a niche-independent adaptive transfer model, JUN steered graft survival and conferred increased self-renewal to fibroblasts. In vivo, JUN enhanced the expression of CD47, and inhibiting CD47 eliminated an ectopic fibroblast graft and increased in vitro phagocytosis. In the syngeneic mouse, depleting macrophages ameliorated skin fibrosis. Therapeutically, combined CD47 and IL-6 blockade reversed skin fibrosis in mice and led to the rapid elimination of ectopically transplanted scleroderma cells. Altogether, our study demonstrates the efficiency of combining different immunotherapies in treating scleroderma and provides a rationale for combining CD47 and IL-6 inhibition in clinical trials.

    View details for DOI 10.1172/jci.insight.140458

    View details for PubMedID 32814713

  • Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures. Stem cell reports Lerbs, T., Cui, L., Muscat, C., Saleem, A., van Neste, C., Domizi, P., Chan, C., Wernig, G. 2020

    Abstract

    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. Nature communications Cui, L., Chen, S. Y., Lerbs, T., Lee, J. W., Domizi, P., Gordon, S., Kim, Y. H., Nolan, G., Betancur, P., Wernig, G. 2020; 11 (1): 2795

    Abstract

    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

  • Elucidating the fundamental fibrotic processes driving abdominal adhesion formation. Nature communications Foster, D. S., Marshall, C. D., Gulati, G. S., Chinta, M. S., Nguyen, A., Salhotra, A., Jones, R. E., Burcham, A., Lerbs, T., Cui, L., King, M. E., Titan, A. L., Ransom, R. C., Manjunath, A., Hu, M. S., Blackshear, C. P., Mascharak, S., Moore, A. L., Norton, J. A., Kin, C. J., Shelton, A. A., Januszyk, M., Gurtner, G. C., Wernig, G., Longaker, M. T. 2020; 11 (1): 4061

    Abstract

    Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Our understanding of adhesion biology is limited, which explains the paucity of anti-adhesion treatments. Here we present a systematic analysis of mouse and human adhesion tissues. First, we show that adhesions derive primarily from the visceral peritoneum, consistent with our clinical experience that adhesions form primarily following laparotomy rather than laparoscopy. Second, adhesions are formed by poly-clonal proliferating tissue-resident fibroblasts. Third, using single cell RNA-sequencing, we identify heterogeneity among adhesion fibroblasts, which is more pronounced at early timepoints. Fourth, JUN promotes adhesion formation and results in upregulation of PDGFRA expression. With JUN suppression, adhesion formation is diminished. Our findings support JUN as a therapeutic target to prevent adhesions. An anti-JUN therapy that could be applied intra-operatively to prevent adhesion formation could dramatically improve the lives of surgical patients.

    View details for DOI 10.1038/s41467-020-17883-1

    View details for PubMedID 32792541

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