FOR 5417:  Translational Polytrauma Research to Provide Diagnostic and Therapeutic Tools for Improving Outcomes

• Subject Area: Medicine
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465409392

Trauma remains a significant cause of morbidity and mortality, particularly in young populations. Despite all advances in research and therapy, it is still not possible to fully explain or predict the clinical course after trauma. To decipher the complex post-traumatic immune and regenerative response, elaborate studies are necessary, requiring close, multicenter collaboration among the participating institutes. This research network between five major trauma centers in Germany (Universities of Frankfurt, Ulm, Aachen, Magdeburg, Erlangen) has emerged from successful joint collaboration in establishing a nationwide biobank for serum/plasma samples from polytrauma patients within the Netzwerk Trauma Forschung (NTF). The network comprises the central project (CP) with the NTF Trauma Bio- and Databank, which is linked to the trauma registry of the DGU, and eight subprojects in a translational approach. The aim is to identify novel mechanisms, potential biomarkers, and treatment strategies and subsequently to test the validity of the newly identified parameters for routine detection in post-traumatic care and rehabilitation using samples from the NTF-Bio- and Databank. This will be reached by combining different experimental approaches, partly using common methodological platforms. The central project (CP) will operate and expand with the NTF biobank and Serum Databank Module of the Trauma Registry and provide clinical data and sample materials to the subprojects. Project F-C involves the development and establishment of a trauma patient extracellular vesicle (EV) biobank and which will be integrated into the CP. Subproject MF-1 will focus on understanding the genetic, molecular, and physiological responses to alcohol exposure in polytrauma that may shift the "balance" of an adaptive response to a pathological response. Subproject F-2 will focus on identifying TBI-specific miRNAs patterns that may aid in the clinical assessment of TBI in polytrauma. Subproject E-1 will focus on understanding the diagnostic and therapeutic potential of microRNAs in relation to cardiac injury after polytrauma. Subproject A-1 is investigating the role of EVs in post-traumatic disorders in cellular and organic cross talk. Subproject A-2 analyzes the role of heparanase, heparan sulfate fragments, and MIF family proteins as diagnostic/therapeutic targets in trauma-induced multi-organ failure. Subproject U-1 will investigate the role of proteases in intestinal innate immunity after experimental and clinical polytrauma and their role in post-traumatic coagulopathy and MODS. The subject of subproject U-2 is the role of age on outcome after combined TBI and hemorrhagic shock. The experimental data from the subprojects in combination with the clinical and experimental data from the NTF Trauma Bio- and Databank will provide a comprehensive, holistic view of the regulatory processes after polytrauma, leading to new insights for individualized patient care and therapy.

• DFG Programme: Research Units

Projects

• Cardiac depression after multiple trauma – diagnostic and therapeutic effects of microRNAs (Applicant Weber, Birte )
• Characteristics of extracellular vesicles and their potential role in organ-cross talk after multiple trauma (Applicants Hildebrand, Frank ;  Horst, Klemens )
• Coordination Funds (Applicant Marzi, Ingo )
• Dysfunction of intestinal mucosal immunity after clinical and experimental polytrauma (Applicant Huber-Lang, Markus )
• Establishment of a nationwide NTF-EV-Biobank from polytraumatized patients: dependency of EV-characteristics in response to the injury pattern (Applicants Marzi, Ingo ;  Weber, Birte )
• Heparanase and macrophage migration inhibitory factor as diagnostic/therapeutic targets in trauma and haemorrhagic shock-associated multiple organ failure (Applicant Martin, Lukas )
• Impact of aging on combined traumatic brain injury and hemorrhage: role of the H2S system (Applicant Merz, Tamara )
• Interaction between posttraumatic inflammatory response in polytrauma patients with and without traumatic brain injury at the posttranscriptional level (miRNA) (Applicant Schindler, Cora )
• Targeting canonical and non-canonical NF-κB deubiquitinating mediators for individualized therapy to improve the outcome in alcohol-intoxicated trauma (Applicant Relja, Borna )

• Spokesperson: Professor Dr. Ingo Marzi