Precision Regenerative Medicine
Chronic disease is most prevalent in the elderly and ultimately stems from a multifactorial combination of aging, genetic predisposition, and lifelong epigenetic priming that together can limit the regenerative capacity of our organs. We focus our work on the mechanistic dissection of human lung biology and aim at pioneering regenerative reprogramming therapy in chronic lung disease patients that will increase the healthspan and resilience of aged and diseased lungs.
Chronic disease is most prevalent in the elderly and ultimately stems from a multifactorial combination of aging, genetic predisposition, and lifelong epigenetic priming that together can limit the regenerative capacity of our organs. We focus our work on the mechanistic dissection of human lung biology and aim at pioneering regenerative reprogramming therapy in chronic lung disease patients that will increase the healthspan and resilience of aged and diseased lungs.
Helmholtz Munich | Lin YangOur Research in a nutshell
Modern single-cell analysis technologies rapidly generate a growing number of cell type and cell state atlases in the healthy and diseased lung. Emerging spatial methods further position the associated gene programs in the context of tissue architecture and enable the systematic deciphering of local cell communication programs. Under disease conditions, ectopic or aberrant cell types or -states regularly emerge, but their significance is often unknown. An outstanding challenge for medical research is 1) to define early deviation points of the lifelong cellular state trajectories from normal to early disease, 2) to explain causative cellular and molecular aberrations driving the disease, 3) to identify suitable intervention junctions to reprogram altered tissue states back to homeostasis and 4) to analyze cellular modes of responsiveness to therapeutic intervention.
Lung disease is the second most common cause of death globally. Even though the lungs' regenerative capacity, which is mediated through different stem cell populations, is very high, the ability for organ regeneration is often lost in the aging process and various chronic lung diseases. We aim to advance experimental systems medicine by analyzing lifelong trajectories spanning pediatric lung health all the way to lung aging to identify individuals at respiratory risk and early stages of disease.
Together with our network of clinical collaborators we leverage single cell multi-omics technologies for observations of cellular and molecular events in different patient cohorts and aim at linking these observations to electronic health records and patient (epi-)genetics. We also work on reverse translation of these ground truths observed in patient samples to human organotypic models as well as mouse models of disease. Using functional single cell genomics and proteomics coupled with generative AI, we interrogate cellular circuit mechanisms in the pre-clinical model systems and going forward aim to translate these insights into preventative and regenerative therapy regimes.
People at PRM
Publications
2024 European Respiratory Journal
Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.
2023 iScience
2023 Science Translational Medicine
2021 EMBO Mol Med
Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers
2020 Nature Communications
2019 Nature Communications
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics.
Selected Preprints
Contact
Funders and Consortia
- German Center for Lung Research (DZL) - Deutsches Zentrum für Lungenforschung (dzl.de)
- Single Cell Omics Germany - Single Cell Omics Germany
- Human Cell Atlas consortium - Home (humancellatlas.org)
- DiscovAIR consortium funded by the European Commission - DiscovAIR
- SkinTerm consortium funded by the European Commission - Home - SkinTERM
- TRR 359 PILOT funded by the German Research Foundation (DFG) - TRR 359 PILOT | perinatal immunity immunology TRR 359 PILOT (perinatal-immunity.de)
- GRK 2338 funded by the German Research Foundation (DFG) - RTG 2338 Targets in Toxicology - LMU Munich (uni-muenchen.de)
- Human Lung Cell Atlas 1.0 consortium funded by the Chan Zuckerberg Initiative - Human Lung Cell Atlas 1.0 - Chan Zuckerberg Initiative
- MPII consortium funded by the Chan Zuckerberg Initiative - Mapping the Pediatric Inhalation Interface: Nose, Mouth, and Airways, - Chan Zuckerberg Initiative
- COVIPA consortium funded by the Helmholtz Association and the Federal Ministry of Education and Research - Virological and immunological determinants of COVID-19 pathogenesis - lessons to get prepared for future pandemics (dkfz.de)
- Postdoctoral Fellowships funded by the European Respiratory Society - ERS (ersnet.org), EMBO – Excellence in life sciences and Home - Marie Skłodowska-Curie Actions (europa.eu).
Research Collaborators
- Prof. Fabian J Theis – Helmholtz Munich, Germany
- Prof. Matthias Mann – Max Planck Institute of Biochemistry, Germany
- Prof. Richard Scheltema – University of Liverpool, UK
- Prof. Purushothama Rao Tata – Duke University, USA
- Prof. Wim Wuyts & Dr. Laurens De Sadeleer – KU Leuven, Belgium
- Prof. Scott Budinger & Prof. Alexander Misharin – Northwestern University Chicago, USA
- Prof. Melanie Königshoff – University of Pittsburgh, USA
- Prof. Christos Samakovlis – SciLife Lab, Sweden
- Prof. Martijn Nawijn – University of Groningen, Netherlands
