Epigenetics of Chronic Lung Diseases
University Liaison Group
Our research focuses on decoding the role of epigenetics in the development, establishment and deterioration of chronic lung diseases. We investigate how influences collectively described as the 'exposome’ (e.g. air pollutants, pathogens, allergens, but also the intestinal microbiome) result in epigenetic changes and lead to aforementioned facilitation of chronic lung disease. In addition to the mechanistic elucidation of epigenetic regulation, our goal as a university liaison group is to develop new biomarkers and innovative therapeutic approaches (theranostics) and translate the investigations into cohorts (ALLIANCE section website; Napkon project) to test.
Looking for bachelor / master thesis, dissertations or interested in doing a medical thesis or a postdoc with us? Feel free to contact us (Our team (uksh.de)!
All-age asthma (ALLIANCE) cohort (CARE & CONTROL)
Our laboratory in Lübeckis significantly involved in patient recruitment, sample processing, measurement and phenotyping of the ALLIANCE cohort (ALLIANCE (All Age Asthma Cohort) - German Center for Lung Research (dzl.de)). As part of the BMBF-funded German Center for Lung Research (DZL), the Department of Pediatric Pneumology & Allergology of UKSH Lübeck (Sektionswebseite- Lübeck (uksh.de)) recruits children and adolescents with asthma and healthy controls. The aim is to develop precision medicine for this heterogeneous disease using high-resolution, clinical and molecular patient characterization.
Epigenetic Landscape in Chronic Lung Diseases (CONTROL)
Epigenetics is characterized by a high level of adaptive processes. This way, epigenetic mechanisms (e.g. micro-RNA or DNA methylation) can react to endogenous and exogenous signals and ensure an optimal response from the organism. In particular, DNA methylation has a high level of plasticity and acts as a cell memory of previous exposures. These exposures are collectively referred to as an exposome and include not only respiratory pathogens (e.g. viruses) but also allergens or (e)cigarette smoke. Also, growth factors, endogenous messenger substances (e.g. cytokines) and hormonesinfluence this cell memory. In an ideal scenario, the cell optimizes the stimulus-specific response. However, there are indications, especially in people with chronic lung disease, that a deleterious memory exists, which promotes the progression of the disease.
We therefore investigate the plasticity and persistence of epigenetic traits in cells from patients with chronic lung diseases. At the same time, we study fundamental mechanisms of how these characteristics form, how they are involved in organ development / organ function and can be passed on or changed in order to develop innovative, therapeutic interventions.
Lung remodeling processes in asthma (and other chronic lung diseases) (CARE)
Serological neo-epitope markers of extracellular matrix (ECM) components of the lung represent a minimally invasive way of measuring lung remodelling processes and thus form a specific signature of disease activity. Among others, we examine collagens and elastin as well as their pro-forms and proteolytic fragments in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF). In addition, we compare them between the chronic lung diseases and against the background of lung development and loss of lung function. We also investigate the epigenetic regulation of ECM proteins after viral infections.
Europäische Union
- Innovative Training Network 'RESPIRE EXCEL’ (EU Maria-Skłodowska-Curie Action) (Project Coordinator: Martijn Nawijn, University of Groningen, Niederlande; Training Coordinator: Markus Weckmann; Science Coordinator: Jenny Mjösberg (Karolinska Institute, Schweden - to be announced)
Bundesministerium für Bildung und Forschung
- Deutsches Zentrum für Lungenforschung (DZL), Research Center North (ARCN)
- Disease Area Asthma / Allergy: All-Age-Asthma- Kohorte
Landesförderung
- Follow-Up of Respiratory Infections Schleswig-Holstein (FRISH) (für HL: Markus Weckmann, Folke Brinkmann)
Industriekooperationen
- Novartis: Predik-TUM
Stiftungen und Gesellschaften
- TBC e.V. - Schleswig Holstein: Epigenetic and genetic evaluation of treatment outcome in patients with multidrug-resistent and drug-sensitive tuberculosis (Maja Reimann, Markus Weckmann, Folke Brinkmann)
Molecular biology methods
- SDS-PAGE, Western blotting
- PCR, preparative agarose gels, qPCR
- Chromatin immunoprecipitation (ChIP)
- Dot Blot
- Immunohistology
Genetic engineering methods (S1 and S2) and next-generation sequencing (NGS)
- E. coli protein expression
- Cloning vector design
- Lipofection
- siRNA
- dCas driven methyltransferases (under development)
- Pyrosequencing, RNA sequencing (pre-analytics)
- Spatial Methylomics
Data science
- Design of Experiments (DoE) layouts
- RNA-Seq analyses (differential expression, enrichments)
- DNA methylation analysis (differential methylations, eQTL)
- Cohort design and cohort analysis (cross-sectional, longitudinal)
Cell biology methods
- Primary cells & mammalian cell lines(?) culture(nasal epithelial cells, peripheral blood cells, wide range of lung cells)
- Air-Liquid Interface cultures
- Infections with human pathogens (e.g. rhinoviruses) or gene carriers (lentiviruses)
- 3D cell migration assay (SiMA)
2024
Abu Risha, M, Reddy, KD, Nemani, SSP, Jakwerth, C, Schmidt-Weber, C, Bahmer, T, Hansen, G, von Mutius, E, Rabe, KF & Dittrich, A-M et al. 2024, 'Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections', ALLERGY. https://doi.org/10.1111/all.16388
Jung, L, Buchwald, IC, Hauck, A, Lüthgen, M, Jagomast, T, Weckmann, M, Drömann, D & Franzen, KF 2024, 'The Impact of Heat-Not-Burn, E-Cigarettes, and Cigarettes on Small Airway Function', Tobacco use insights, Jg. 17, S. 1179173X241271551. https://doi.org/10.1177/1179173X241271551
2022
Kopp MV, Weckmann M, Nissen G, Ricklefs I, Härtel C. Two Beer(s) or Not Two Beer(s): The eNose as an Instrument to Pacify the World. Klin Padiatr. 2022 Feb 9. doi: 10.1055/a-1714-8895. Online ahead of print. PMID: 35139542 English.https://pubmed.ncbi.nlm.nih.gov/35210326/
Maison N, Omony J, Illi S, Thiele D, Skevaki C, Dittrich AM, Bahmer T, Rabe KF, Weckmann M, Happle C, Schaub B, Meier M, Foth S, Rietschel E, Renz H, Hansen G, Kopp MV, von Mutius E, Grychtol R; ALLIANCE Study Group. T-high asthma phenotypes across life span. Eur Respir J. 2022 Feb 24:2102288. doi: 10.1183/13993003.02288-2021. Online ahead of print. PMID: 35210326
Rønnow SR, Sand JMB, Staunstrup LM, Bahmer T, Wegmann M, Lunding L, Burgess J, Rabe K, Sorensen GL, Fuchs O, Mutius EV, Hansen G, Kopp MV, Karsdal M, Leeming DJ, Weckmann M; ALLIANCE Study Group as part of the German Center of Lung Research (DZL). A serological biomarker of type I collagen degradation is related to a more severe, high neutrophilic, obese asthma subtype. Asthma Res Pract. 2022 Apr 13;8(1):2. doi: 10.1186/s40733-022-00084-6.PMID: 35418159 Free PMC article.
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