Project Z2

The CRU Pemphigoid Diseases aims at comprehensively modeling the processes driving the effector phase of pemphigoid diseases (PDs) and at exploiting these new insights to develop new therapeutics and diagnostics for these disease entities. In recent years, state-of-the-art statistical analysis and systems medicine modeling has facilitated the elucidation of complex, heterogeneous diseases. Our CRU will therefore apply these techniques to PDs. For this purpose, we will establish a CRU core unit (“Z2-Project”) for Biostatistics & Systems Medicine. This core unit will operate as service and independent research unit of the CRU. Among others, it will analyze the data compiled in the PD patient database of the Z1-Project in all its dimensions. This will include basic and mechanistic epidemiological studies, in which PD patients will be deep-phenotyped in order to distinguish PD patient subgroups, to define individual and environmental risk factors for PD, as well as predictors of prognosis and drug response. This will further delineate the pathogenesis of PDs and will facilitate the implementation of personalized “precision medicine” strategies in PD patient care.
Additionally, the core unit will analyze the genome and microbiome data generated in Projects 1 and 2 and use these to model gene networks and gene-microbiota-disease interactions. Finally, it will integrate all data generated in the CRU for a pathway analysis, modeling the processes of the PD effector phase on the molecular level. Using this model, biomarkers and molecular pathways relevant for the pathogenesis of PD will be identified and new hypotheses on the pathogenesis of PD will be postulated, which will be subsequently examined in the running CRU projects or in the 2nd CRU funding period. Thus, the Z2-Project will be pivotal to set the future directions of the CRU.
The core unit will also provide services to all individual CRU projects by statistical analyses and mathematical modeling. Thus, it will also help to predict the expectable extent of clinical benefit generated by newly identified potential biomarkers and drug targets.
Prof. Inke König (Department of Medical Biometry and Statistics), a leading expert in biomathematical analysis and modeling of complex diseases, and Prof. Jeanette Erdmann (Department of Integrative and Experimental Genomics), who is specialized in systems medicine and population genetics, will therefore head this project. The CRU coordinator Dr. Christian Sadik will interpret the results of the Z2-Project in the clinical context and with respect to all results generated in the individual CRU projects. He will use this information to direct the evolvement of the CRU projects towards translation.
Modeling of Pemphigoid Disease Pathogenesis.

• Search for Patient subgroups
• Epidemiology
• Preparation of Clinical Trials