Our research areas (RA) “Imbalanced Inflammation & Infection“, „Fibrotic Repair & Remodeling“ and „Cancer Evolution & Progression“ represent a large number of the most compromising and devastating diseases, hence a large percentage of human disabilities. Together they also account for a larger portion of deaths worldwide (http://www.who.int). Taking the lung as an example, it becomes apparent that pneumonia, idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH) and lung cancer all represent diseases with a serious fatality rate and, in case of lung cancer and IPF, an average life expectancy of still no more than 2-3 years at best (European Lung White Book; www.erswhitebook.org). Likewise, liver cirrhosis and infectious and inflammatory bowel disease, although somewhat less dreadful, also represent most serious diseases, with an enormous impact on survival and life quality. The prospect of some of these diseases have only marginally improved over the last years, clearly underlying the unmet need for novel diagnostic (e.g. early detection or disease stratification) and therapeutic concepts.
In the RA “Imbalanced Inflammation & Infection”, we will therefore study the delicate balance between exaggerated inflammation aiming at pathogen removal, and preservation and re-establishment of organ function by strategies limiting inflammatory injury and fostering tissue regeneration and repair. Apart from these “host-centered” therapeutic approaches, we will also focus on delineating mechanisms of antimicrobial resistance acquisition that are needed for the development of novel antimicrobial treatment options.
In the RA “Fibrotic Repair & Remodeling”, we will elucidate triggering factors in parenchymal organ fibrosis and vascular / cardiac remodeling, we will define involved stem cell niches and pools driving epithelial regeneration in response to injury and the role of developmental pathways in their activation, and we will dissect epigenetic changes in mesenchymal cell populations underlying fibrosis and remodeling.
In the RA “Cancer Evolution & Progression”, we will focus on the interplay between tumor microenvironment signaling, epigenetic and metabolic programming as key cancer hallmarks in controlling tumor malignancy, and therapy resistance, and develop further early detection methods and biomarkers for improved cancer diagnosis and therapy.
Apart from disease-specific pathomechanisms, these RAs nevertheless show significant pathomechanistic overlap and, at least in part, causative relationship. In this line and as typical examples, the etiologic role of virus infection has been proven for both, parenchymal organ fibrosis (e.g. hepatitis virus in liver cirrhosis as well as malignant diseases (e.g. human papillomavirus in cervix carcinoma). Virus infections may interfere with the host immune system (e.g. AIDS), thereby profoundly modifying inflammatory responses. Likewise, bacterial infection and / or changes in the microbiota have been shown to contribute to cancer development (as discussed in colon cancer) and to organ fibrosis (as in lung fibrosis). In addition, many auto-immune diseases have been described to result from structural similarities between host and pathogen antigens („molecular mimicry“) or from alterations in antigen-presentation (as discussed in rheumatoid arthritis). Similarly, disease-specific changes in the affected organ can promote and aggravate other diseases, e.g. lung and liver tumors often develop in the setting of organ fibrosis or inflammation and/or make use of similar programs such as Epithelial to Mesenchymal Transition (EMT). The strong representation of the above mentioned RAs within the Faculty of Human Medicine of the Justus-Liebig-University of Giessen therefore not only allows a focused research within each of these RAs, it also provides a basis for an overarching research approach, aiming to better understand joint triggers, common pathways, and mutual interference between these.
The Clinical Scientists working on the scientific aims will be trained in their respective research groups, covering a broad range of state-of-the-art technologies and methodological platforms.