SFB 1149: Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma

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Trauma can affect any individual at any time. The subsequent danger response, modulated by various individual disturbance factors, strives to induce regenerative processes, but can also represent a major driver of complications and fatal outcome. In the 2nd funding period, the consortium provided many novel mechanistic insights in the trauma response. In the 3rd funding period, the focus of the CRC1149 remains on the most frequent injury patterns (TBI, thorax trauma, fracture). The profile of confounding factors is expanded to reflect the entire lifespan. The investigations address mechanisms of compromised regeneration processes, and aim to provide a detailed pathomechanistic understanding of the molecular trauma response. In many projects, including a transfer project, an emphasis is set on the translation of meaningful research results. The trauma research profile of the Ulm University campus will facilitate realization of the integrative and translational approaches. These include a cross-discipline Trauma Research Centre Ulm (ZTF) with the CRC1149 as its central pillar, the long-standing commitment of the Medical Faculty to cutting-edge research in trauma, and the recent founding of a new research building on Multidimensional Trauma Sciences (MTW). As compelling scientific and clinical challenges, we pursue the central hypotheses of the CRC1149, to: A) elucidate the danger response after trauma on a molecular, cellular, organ, and organism level; B) determine the influence of major disturbance factors (co-morbidities) on the trauma response; C) define mechanisms and potential of regeneration post trauma and adapt them to trauma management. These hypotheses are reflected on by three highly interactive project groups (A, B, C), one transfer project (T01), and one central platform (Z02), combining excellent basic-science, translational, and clinical expertise: Research group A will investigate the mechanisms of the spatial-temporal, neuroinflammatory, immune, and cellular acute danger responses post trauma, and the subsequent consequences on cross-talking organs. Research group B will address the modulation and perturbation of the trauma responses by relevant confounding factors, including co-morbidities (aging, diabetes, atherosclerosis, osteoporosis, Parkinson’s disease), lifestyle habits (ethanol), acute stress, and experienced psychosocial trauma (early life stress). Research group C aims to improve the resolving and regenerative capacity in models of fracture, wounds, TBI and peripheral nerve trauma, accomplished by immune cells, stress hormones, progenitor cells and genetic regulators. In cooperation with a start-up pharma, the transfer project investigates inhibition of thromboinflammation in human extra-corporal membrane oxygenation/hemodialysis ex vivo models. Most projects include mechanistic evaluation of promising novel therapeutic approaches with the final aim of reducing the burden of trauma for the individual and society.