Scientists identify ‘traumome’ targets for rapid emergency trauma treatment
Researchers have discovered a molecular fingerprint called the “traumome” that becomes accessible within minutes of severe injury. The breakthrough could enable targeted treatments to be delivered directly to trauma sites, with the potential to significantly advance emergency trauma care for patients with life-threatening injuries.
Rutgers Health researchers have identified a novel approach to treating severe trauma by targeting a previously unknown network of calcium-dependent proteins that become accessible immediately following injury. This discovery, published in Med on 11 July 2025, introduces the concept of the “traumome” – a functional receptor repertoire that emerges rapidly after major tissue damage.
Calcium-dependent protein network emerges after injury
The research team, led by Renata Pasqualini and Wadih Arap at the Rutgers Cancer Institute, used an innovative phage display screening approach in a porcine model of compound femur fracture with haemorrhagic shock. Their systematic analysis revealed 23 injury-specific ligand peptides, with nearly all corresponding receptors being calcium-dependent proteins.
“The moment trauma occurs, specific proteins undergo structural changes, creating a molecular footprint of injury,” said Arap. “This opens the door to delivering diagnostics or therapies directly to the site – without affecting healthy tissues.”
The study demonstrated that when cells are damaged during major trauma, intracellular calcium levels spike dramatically. This calcium influx causes specific proteins to change their three-dimensional structure, making them accessible to circulating targeting molecules for the first time.
Molecular imaging confirms trauma-specific targeting
The researchers validated their findings using advanced molecular imaging techniques including positron emission tomography/magnetic resonance imaging (PET/MRI) and single-photon emission computerised tomography/computed tomography (SPECT/CT). One particularly promising ligand peptide, CRQRPASGC, demonstrated specific binding to calreticulin (CALR) – a calcium-dependent protein that becomes uniquely accessible at injury sites.
In both porcine and rat models, radiolabelled CRQRPASGC showed progressive accumulation at trauma sites within 30 minutes of administration, with minimal uptake in healthy tissues. The targeting was maintained for up to five hours post-injury, providing a substantial therapeutic window.
Potential applications in emergency medicine
The implications for emergency treatment are significant. Current trauma therapies often affect healthy organs when administered systemically, potentially causing adverse effects. The traumome concept could enable delivery of treatments including imaging agents, clotting factors, or antibiotics directly to injured areas.
“Our long-term vision is a simple injection that autonomously finds and treats injury sites,” said Pasqualini. “This could be transformative for battlefield medicine and emergency trauma care, where every second matters.”
The research was supported by the US-based Defence Advanced Research Projects Agency (DARPA), highlighting its strategic importance for military applications. Jon Mogford, a study co-author and former DARPA official, noted: “Non-compressible bleeding remains a leading cause of death among soldiers before they reach a hospital, and localised treatment could dramatically improve survival rates, which was the original impetus of this research.”
Understanding the traumome mechanism
The study’s molecular dynamics simulations and structural analysis revealed how calcium binding stabilises specific protein conformations that become targetable after trauma. The team found that CRQRPASGC targets a calcium-facilitated conformational state of calreticulin, specifically binding to the protein’s C-terminus.
As the authors explain in their discussion: “We conceptually propose the term ‘traumome’ for the functional receptor repertoire that becomes readily amenable for ligand-directed targeting upon major trauma. These preclinical findings pave the way toward clinic-ready targeted theragnostic approaches in the setting of trauma.”
The researchers demonstrated that this targeting mechanism is conserved across mammalian species, with trauma-targeting peptides showing similar efficacy in both pig and rat models, suggesting potential translatability to human patients.
Clinical translation pathway
The next phase involves linking therapeutic agents to trauma-homing peptides and testing them in animal models before progressing to human clinical trials. The team envisions applications ranging from battlefield medicine to civilian emergency response, and potentially extending to sports injuries or surgical recovery.
The study also revealed that the traumome may encompass broader applications beyond acute trauma. “The traumome concept may also have applications beyond trauma, including in surgery, inflammation and tissue regeneration,” said Arap.
Technical challenges and future development
The research identified several technical considerations for clinical development. The team found that certain peptide mutations could serve as more appropriate negative controls for future studies, and larger, more diverse cohorts will be needed to fully characterise the targeting attributes beyond preclinical settings.
The concept of conformational targeting represents a paradigm shift in trauma medicine, potentially enabling the development of “smart” therapeutics that activate only at injury sites. This approach could address the critical “golden hour” timeframe in trauma care, where rapid intervention is essential for patient survival.
The study’s comprehensive approach, combining phage display screening, molecular imaging, and computational modelling, provides a robust foundation for translating this discovery into clinical applications that could fundamentally change how severe trauma is treated.
Reference
Pasqualini, R., Markosian, C., Arap, W. et. al. (2025). Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma. Med, 6, 100638. https://doi.org/10.1016/j.medj.2025.100638
