Principal Investigators

Dr. med. Thomas Pap (PI)
Joanna Sherwood, PhD (Co-PI)
Dr. med. univ. Adelheid Korb-Pap (Co-PI)
Prof. Dr. med. Thomas Kamradt (PI)
Prof. Dr. med. Ulf Müller-Ladner (PI)
PD Dr. rer. nat Elena Neumann (Co-PI)
LysatPharma GmbH c/o Kyra de Miroschedji,

Additional Partners

Dr. med. Tobias Ruck (PI)
Prof. Dr. med. Heinz Wiendl (Co-PI)
Prof. Dr. med. Bettina Löffler (PI)
PD Dr. Lorena Tuchscherr de Hauschopp (Co-PI)
PD Dr. med. dent. Ulrike Schulze-Späte (PI)
Prof. Dr. med. Gabriela Riemekasten* (PI)
PD Dr. med. Tanja Lange* (Co-PI)
Xinhua Yu, PhD** (Co-PI)
Dr. rer. nat. Lars-Oliver Tykocinski (PI)
Dr. rer. nat. Theresa Tretter (Co-PI)
Prof. Dr. med. Hanns-Martin Lorenz (Co-PI)
Prof. Dr. med. Peter Lamprecht *(PI)
Prof. Dr. med. Udo Schumacher** (Co-PI)

Abstract

Although chronic inflammatory musculoskeletal disorders (IMDs) share significant similarities in their effector phases, they show variable organ involvement and different, but overlapping inflammatory tissue reactions. Genetic and epigenetic profiling of mesenchymal cells from IMDs have revealed specific signatures supporting the idea that the local mesen- chyme is central for the organ specificity of the individual IMDs. Nonethe- less, little is known about how such signatures initiate and perpetuate the specific disease patterns, and whether targeting the local mesenchyme may help to treat IMDs. By investigating different IMDs, this interdiscipli- nary research consortium will follow the hypothesis that the local mesen- chyme regulates disease manifestation and severity, and that its targeting will provide novel therapeutic strategies for IMDs. To test and validate this hypothesis, we will set up an integrative Clinical Translational Platform (CTP) that will enable the structured and comparative analysis of human IMD samples, disease signatures, mechanisms and pathways as well as the analysis of disease- and pathway-specific animal models. Using a common technology platform with state-of-the-art techniques including 3rd generation mass cytometry, automated cytokine profiling, epigenome and proteomic analysis, we will i) characterize human and murine IMD sam- ples via standardized approaches including their acquisition and handling, ii) share murine models of IMDs including genetically modified mice and iii) jointly test novel therapeutic approaches in standardized in vitro- and in vivo settings. In addition to deepening our understanding of tissue- specific mechanisms of IMDs, this strategy will generate novel information to predict tissue- specific drug effects by generating a future “atlas” of distinct and shared signatures in IMDs. Moreover, the CTP will use the expertise of our start-up company partner to preclinically test novel, extra- cellular vesicle-based treatment strategies. This cross-disciplinary CTP will also provide a valuable data repository and models for a rational pre- diction of actual and future therapeutic interventions in the individual IMD.

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