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

创伤可以在任何时候影响任何人。随后的危险反应，由各种个体干扰因素调节，努力诱导再生过程，但也可以代表并发症和致命结果的主要驱动因素。在第二个资助期，该联盟在创伤反应中提供了许多新的机制见解。在第三个资助期，CRC1149的重点仍然是最常见的损伤模式（TBI，胸腔创伤，骨折）。混杂因素的概况扩大到反映整个生命周期。研究涉及受损再生过程的机制，旨在提供分子创伤反应的详细病理机制理解。在许多项目中，包括一个转移项目，重点是翻译有意义的研究成果。乌尔姆大学校园的创伤研究概况将促进综合和转化方法的实现。其中包括以CRC1149为中心支柱的乌尔姆跨学科创伤研究中心（ZTF），医学院对创伤前沿研究的长期承诺，以及最近建立的多维创伤科学（MTW）的新研究大楼。作为迫切的科学和临床挑战，我们追求CRC1149的中心假设：A)在分子、细胞、器官和生物体水平上阐明创伤后的危险反应；B)确定主要干扰因素（合并症）对创伤反应的影响；C)明确创伤后再生的机制和潜力，并使其适应创伤管理。这些假设反映在三个高度互动的项目小组（A， B， C），一个转移项目（T01）和一个中心平台（Z02），结合优秀的基础科学，转化和临床专业知识：研究小组A将研究创伤后时空，神经炎症，免疫和细胞急性危险反应的机制，以及随后对交叉器官的影响。B研究组将研究相关混杂因素对创伤反应的调节和干扰，包括合并症（衰老、糖尿病、动脉粥样硬化、骨质疏松症、帕金森病）、生活习惯（酒精）、急性压力和经历过的心理创伤（早期生活压力）。C研究组旨在通过免疫细胞、应激激素、祖细胞和遗传调节因子来提高骨折、创伤、TBI和周围神经损伤模型的修复和再生能力。该转移项目与一家初创制药公司合作，研究了人体体外膜氧合/血液透析体外模型对血栓炎症的抑制作用。大多数项目包括对有前途的新治疗方法的机械评估，最终目的是减轻个人和社会的创伤负担。

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.