Research
- Research Topics
- Cell Biology and Tumor Biology
- Stem Cells and Cancer
- Inflammatory Stress in Stem Cells
- Experimental Hematology
- Molecular Embryology
- Signal Transduction and Growth Control
- Epigenetics
- Redox Regulation
- Vascular Oncology and Metastasis
- Clinical Neurobiology
- Molecular Neurogenetics
- Chaperones and Proteases
- Vascular Signaling and Cancer
- Molecular Neurobiology
- Mechanisms Regulating Gene Expression
- Molecular Biology of Centrosomes and Cilia
- Dermato-Oncology
- Pediatric Leukemia
- Molecular Hematology - Oncology
- Cancer Progression and Metastasis
- Metastatic Niches
- Molecular Leukemogenesis
- DNA Repair Mechanisms and Cancer
- Neuronal Signaling and Morphogenesis
- Cell Signaling and Metabolism
- Cell Fate Engineering and Disease Modeling
- Cancer Drug Development
- Cell Morphogenesis and Signal Transduction
- Tumour Metabolism and Microenvironment
- Helmholtz Professorship Cell Biology
- Functional and Structural Genomics
- Molecular Genome Analysis
- Molecular Genetics
- Pediatric Neurooncology
- Cancer Genome Research
- Chromatin Networks
- Functional Genome Analysis
- Theoretical Systems Biology
- Neuroblastoma Genomics
- Signaling and Functional Genomics
- Signal Transduction in Cancer and Metabolism
- RNA Biology and Cancer
- Systems Biology of Signal Transduction
- Molecular thoracic Oncology
- Proteomics of Stem Cells and Cancer
- Computational Genomics and System Genetics
- Regulatory Genomics and Cancer Evolution
- Applied Functional Genomics
- Applied Bioinformatics
- Translational Medical Oncology
- Cancer Epigenomics
- Translational Pediatric Sarcoma Research
- Neuropathology
- Pediatric Oncology
- Neurooncology
- Somatic Evolution and Early Detection
- Translational Control and Metabolism
- Pediatric Glioma Research
- Soft-Tissue Sarcoma
- Precision Sarcoma Research
- Neural Stem Cell Genome Integrity in Brain Development and Diseases
- Mechanisms of Leukemogenesis
- Genome Instability in Tumors
- Developmental Origins of Pediatric Cancer
- Brain Tumor Translational Targets
- Brain Cancer Metabolism
- Translational Functional Cancer Genomics
- SPRINT
- Cancer Risk Factors and Prevention
- Cancer Epidemiology
- Biostatistics
- Clinical Epidemiology and Aging Research
- Health Economics
- Physical Activity, Prevention and Cancer
- Preventive Oncology
- Digital Biomarkers for Oncology
- Genomic Epidemiology
- Cancer Survivorship
- Molecular Epidemiology
- Immunology and Cancer
- Cellular Immunology
- Molecular Oncology of Gastrointestinal Tumors
- Translational Immunotherapy
- B Cell Immunology
- Immune Diversity
- Structural Biology of Infection and Immunity
- Applied Tumor-Immunity
- Neuroimmunology and Brain Tumor Immunology
- T Cell Metabolism
- Adaptive Immunity and Lymphoma
- Immune Regulation in Cancer
- GMP & T Cell Therapy
- News
- Imaging and Radiooncology
- Radiology
- Research
- Computational Radiology Research Group
- Contrast Agents In Radiology Research Group
- Neuro-Oncologic Imaging Research Group
- Radiological Early Response Assessment Of Modern Cancer Therapies
- Imaging In Monoclonal Plasma Cell Disorders
- 7 Tesla MRI - Novel Imaging Biomarkers
- Functional Imaging
- Visualization And Forensic Imaging
- PET/MRI
- Dual- and Multienergy CT
- Radiomics Research Group
- Prostate Research Group
- Breast Imaging Research Group
- Bone marrow
- Musculoskeletal Imaging
- Staff
- Patients
- Research
- Medical Physics in Radiology
- X-Ray Imaging and Computed Tomography
- Medical Informatics for Translational Oncology
- Federated Information Systems
- Medical Physics in Radiation Oncology
- Biomedical Physics in Radiation Oncology
- Computer Assisted Medical Interventions
- Medical Image Computing
- Radiooncology - Radiobiology
- Radiation Oncology
- Molecular Radiooncology
- Nuclear Medicine
- Medical Imaging and Radiology - Cancer Prevention
- Molecular Biology of Systemic Radiotherapy
- Translational Radiation Oncology
- Molecular Mechanisms of Head and Neck Tumors
- Radiology
- Infection, Inflammation and Cancer
- Tumor Virology
- Viral Transformation Mechanisms
- Pathogenesis of Virus-Associated Tumors
- Applied Tumor Biology
- Virotherapy
- Virus-associated Carcinogenesis
- Chronic Inflammation and Cancer
- Microbiome and Cancer
- Cell Plasticity and Epigenetic Remodeling
- Cellular Polarity and Viral Infection
- Noroviruses
- Laboratory of Oncolytic Virus Immuno-Therapeutics
- Infections and Cancer Epidemiology
- Tumorvirus-specific Vaccination Strategies
- Mammalian Cell Cycle Control Mechanisms
- Molecular Therapy of Virus-Associated Cancers
- Immunotherapy and Immunoprevention - Molecular Vaccine Design
- DNA Vectors
- Episomal-Persistent DNA in Cancer- and Chronic Diseases
- Other Units
- Cell Biology and Tumor Biology
- Research Groups A-Z
- Junior Research Groups
- Core Facilities
- Center for Preclinical Research
- Chemical Biology Core Facility
- Electron Microscopy
- Flow Cytometry
- Genomics and Proteomics
- Information Technology
- Library
- Kataloge - Catalogues
- Zeitschriften - Journals
- E-Books - Ebooks
- Datenbanken - Databases
- Dokument-Lieferung - Document Delivery
- Publikationsdatenbank - Publication database
- DKFZ Archiv - DKFZ Archive
- Open Access
- Science 2.0
- Ansprechpartner - Contact
- More Information - Service
- Anschrift - Address
- Antiquariat - Second Hand
- Aufstellungssystematik - Shelf Classification
- Ausleihe - Circulation
- Benutzerhinweise - Library Use
- Beschaffungsvorschläge - Desiderata
- Fakten und Zahlen - Facts and Numbers
- Kooperationen, Konsortien - Cooperations, Consortia
- Kopieren, Scannen - Copying, Scans
- Kurse, Führungen - Courses, Introductions
- Öffnungszeiten - Opening Hours
- DEAL-Info
- DKFZ-Intern - internal only
- Light Microscopy
- Omics IT and Data Management Core Facility
- Small Animal Imaging
- Metabolomics Core Technology Platform
- Data Science @ DKFZ
- INFORM
- Databox
- Baden-Württemberg Cancer Registry
- Cooperations & Networks
- National Cooperations
- International Cooperations
- Cooperational Research Program with Israel: DKFZ - MOST in Cancer Research
- Program
- Members of the Program Committee
- Call 2019
- Publication Database
- German-Israeli Cancer Research Schools
- Archive
- Heidelberg - Israel, Science and Culture
- Symposium 40 Years of German-Israeli Cooperation
- 35th Anniversary Symposium
- 34th Meeting of the DKFZ-MOST Program
- 40th Anniversary Publication
- 30th Anniversary Publication
- 20th Anniversary Publication
- Flyer - The Cancer Cooperation Program
- List Publications 1976-2004
- Highlight-Projects
- Cooperational Research Program with Israel: DKFZ - MOST in Cancer Research
- Cooperations with industrial companies
- Helmholtz Alliances
- DKFZ PostDoc Network
- Cross Program Topic RNA@DKFZ
- Cross Program Topic Epigenetics@dkfz
- Cross Program Topic Single Cell Sequencing
- WHO Collaborating Centers
- DKFZ Site Dresden
Epigenetic mechanisms in radiation-induced fibrosis
Fibrosis is an adverse effect of radiation therapy which occurs in 20-30% of patients even years after therapy. It is largely unpredictable and can severely impair quality of life. No efficient treatments are currently available to prevent or reverse fibrotic disease.Our recent findings strongly support the importance of epigenetic dysregulation in both radiation response and fibrotic processes. We developed cellular models for myofibroblast activation using dermal fibroblasts from breast cancer patients collected prior to irradiation. Using a genome-wide DNA methylation screen we identified differentially methylated regions (DMRs) of high interest which were associated with fibrosis and indicate new molecular mechanisms for radiation-induced fibrosis. As an example, we characterized one site as a differentially methylated enhancer of the diacylglycerol kinase alpha (DGKA) gene. Low DNA methylation at this enhancer enabled activation of profibrotic transcription factors and increased radiation-induced DGKA transcription specifically in cells from patients later developing fibrosis.
© dkfz.de
We now aim to develop this novel mechanism further as a way to mitigate predisposition to fibrosis and to improve radiotherapy outcome in cancer survivors. Possible approaches are
- modulating DGKAeffects by pharmacologically targeting the histone pattern at the DGKA enhancer with small molecules inhibiting epigenetic modifiers,
- exploring further stress-inducible enhancers as potential players in key fibrotic processes such as short-term activation of fibroblast or perpetuation of the activates state in fibrotic tissue.
Results will contribute to the understanding of how regulatory genomic elements affect gene expression and how they are driven by epigenetics with the final goals of uncovering the epigenetic pathogenesis of fibrotic disease and using this knowledge for improving radiotherapy.
This work is done in collaboration with the Klinik für Strahlentherapie und Onkologie at the Universitätsmedizin Mannheim and funded by Deutsche Krebshilfe.
Publications:
Weigel C, Schmezer P, Plass C, Popanda O. Epigenetics in radiation-induced fibrosis. Oncogene. 2015 Apr 23;34(17):2145-55. doi: 10.1038/onc.2014.145. Epub 2014 Jun 9. Review. Abstract
Weigel C, Veldwijk MR, Oakes CC, Seibold P, Slynko A, Liesenfeld DB, Rabionet M, Hanke SA, Wenz F, Sperk E, Benner A, Rösli C, Sandhoff R, Assenov Y, Plass C, Herskind C, Chang-Claude J, Schmezer P, Popanda O. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis. Nat Commun. 2016 Mar 11;7:10893. doi: 10.1038/ncomms10893. Abstract
Valinciute G, Weigel C, Veldwijk MR, Oakes CC, Herskind C, Wenz F, Plass C, Schmezer P, Popanda O. BET-bromodomain inhibitors modulate epigenetic patterns at the diacylglycerol kinase alpha enhancer associated with radiation-induced fibrosis. Radiother Oncol. 2017 Oct;125(1):168-174. doi: 10.1016/j.radonc.2017.08.028. Epub 2017 Sep 12. Abstract