Impact Report—Labs—Translational Research

Labs
Translational Research

 

Accidental injuries are a leading cause of death and disability worldwide, affecting over 3 million individuals in the U.S. annually. Rapid access to emergency and intensive care services allows patients to survive severe injuries once lethal. While fortunate to survive the initial injury, these patients are susceptible to morbidity and mortality from a multitude of potential adverse outcomes during and after their hospital admission. Early in convalescence, patients are susceptible to life-threatening bleeding, infection, and thrombotic conditions; all of which may contribute to acute multi-organ dysfunction syndrome (MODS), the principal cause of mortality following the first day of injury. If the patient survives, they are susceptible to developing a post-injury ‘long-hauler’ syndrome (LHS) hallmarked by chronic organ dysfunction. In the musculoskeletal system, post-injury LHS (ie. MSK-LHS) includes pathologies such as impaired fracture healing, development of heterotopic ossification, and osteoporosis. The clinical significance of MSK-LSH is clear as it prevents a patient from returning to their pre-injury health, performing activities of daily living, and is a source of causes chronic pain.

Translational research being conducted by Drs. Jon Schoenecker, MD PhD and Stephanie Moore-Lotridge, PhD is working to fill in key knowledge gaps in the molecular mechanisms driving adverse outcomes of early convalescence and MSK-LHS following severe injury. Upon completion, findings from these studies will help improve prognosis and the development of novel pharmacologic treatments aim at improving patient outcomes. Aligning with these goals, Dr. Mariel Rickert, MD (PGY4) & Dr. Jonathan Savakus, MD (PGY5) each received resident research grants from the OREF and the OTA to support elements of this overarching project. Dr. Rickert is examining the molecular mechanisms driving MODS, specifically examining changes in inflammation and coagulation relative to injury severity. Dr. Savakus is examining how intramedullary nailing can act as a “second hit”, thereby altering measures of inflammation and coagulation in patients with isolated or polytraumatic injuries.

Paralleling these translational, Drs. Schoenecker and Moore-Lotridge are working with Dr. Jeffry Nyman, PhD to develop and characterize a murine model of polytrauma that recapitulate clinical features including MSK-LHS as well as cognitive defects. By developing such a model, their research team will be able to sensitively assess contributing molecular mechanisms and novel therapeutics aimed at improving outcomes.


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