Project Details
SFB 1149: Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma
Subject Area
Medicine
Biology
Biology
Term
since 2015
Website
Homepage
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 251293561
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.
DFG Programme
Collaborative Research Centres
Current projects
- A01 - Neuro-renal crosstalk as immune-modulator of trauma-related acute kidney injury and MODS (Project Head Huber-Lang, Markus )
- A02 - Modulation of synaptic plasticity after trauma (Project Head Böckers, Tobias )
- A03 - Cell-type-specific modulation of NF-ĸB in traumatic brain injury (Project Head Wirth, Thomas )
- A05 - Cellular and molecular responses to trauma-induced damage of the distal respiratory epithelium (Project Heads Barth, Holger ; Frick, Manfred )
- A06 - Therapeutic targeting of small extracellular vesicle (sEV) release and uptake in post-traumatic hyper-inflammation (Project Head Seufferlein, Thomas )
- A07 - Role of myeloid-derived suppressor cells (MDSCs) in post-traumatic and post-septic immune regulation (Strauß (Project Head Strauß, Gudrun )
- A09 - The role of white adipose tissue in post-traumatic inflammation and organ dysfunction (Project Heads Fischer-Posovszky, Pamela ; Halbgebauer, Rebecca )
- B03 - Oxytocin and H2S after TBI and hemorrhage with pre-existing early life stress (Project Heads Merz, Tamara ; Radermacher, Peter Leonhard )
- B05 - Circular RNAs modulate neuronal vulnerability, neuroinflammation and regeneration and are affected by TBI comorbidities (Project Head Roselli, Ph.D., Francesco )
- B06 - Effects of early life stress on bone homeostasis and fracture healing (Project Heads Haffner-Luntzer, Melanie ; Reber, Stefan O. )
- B08 - Effects of peripheral and CNS trauma on the brains of healthy and Parkinson´s Disease mouse models (Project Heads Danzer, Karin ; Dimou, Leda )
- B09 - Elucidating the pathomechanisms of compromised fracture healing in osteoporosis: Consequences of mitochondrial dysfunction (Project Heads Ignatius, Anita ; Riegger-Koch, Jana )
- C02 - Osteoblast differentiation-stage specific mechanisms of glucocorticoid action during fracture healing (Project Heads Ignatius, Anita ; Tuckermann, Jan )
- C03 - Intrinsic heterogeneity and interactions with niches regulate trauma-induced osteoblast dedifferentiation and migration during zebrafish regeneration (Project Head Weidinger, Gilbert )
- C05 - Role of ABCB5+ MSCs in niche homeostasis and repair after trauma (Project Head Scharffetter-Kochanek, Karin )
- C06 - Enhancing recovery after traumatic brain injury (TBI) by genetic and pharmacological modulation of the PTEN/Akt pathway (Project Head Knöll, Bernd )
- C08 - Glucocorticoids influence Schwann cell and macrophage responses in a mouse model of peripheral nerve injury (Project Heads Meyer zu Reckendorf, Sofia ; Vettorazzi, Sabine )
- Z01 - Central tasks of the Collaborative Research Centre (Project Head Gebhard, Florian )
- Z02 - Central project for trauma modeling, monitoring and diagnostics (Project Heads Huber-Lang, Markus ; Ignatius, Anita ; Rasche, Volker )
Completed projects
- A04 - Cell type-selective carriers for targeted pharmacological inhibition of Rho-/actin-dependent leukocyte recruitment into the alveolar space after blunt chest trauma (Project Heads Barth, Holger ; Weil, Tanja )
- A08 - Role of NG2-glia in different injury paradigms (Project Head Dimou, Leda )
- B02 - H2S-induced modulation of the trauma response in nicotine-induced COPD and diabetes (Project Heads Huber-Lang, Markus ; Radermacher, Peter Leonhard )
- B04 - Role of severe obesity on healing of muscle injuries (Project Heads Knippschild, Uwe ; Wabitsch, Martin )
- B07 - Effects of impaired glucocorticoid receptor function in hemorrhagic shock-induced lung injury with pre-existing cigarette smoke-induced chronic obstructive pulmonary disease (Project Heads Vettorazzi, Sabine ; Wepler, Martin )
- C01 - Mechanisms of interleukin-6 action in trauma-induced impairment of bone regeneration (Project Head Ignatius, Anita )
- C04 - The role of stem cell circulation in trauma (Project Head Geiger, Hartmut )
- C07 - Cardiac function after trauma and MSC-based regenerative strategies (Project Heads Kalbitz, Miriam ; Schrezenmeier, Hubert )
- Z03 - Trauma diagnostics (Project Heads Ignatius, Anita ; Rasche, Volker )
Applicant Institution
Universität Ulm
Participating Institution
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Standort Ulm
Standort Ulm
Spokesperson
Professor Dr. Florian Gebhard