Understanding the mechanisms of muscle catabolism after burn injury

The National Institute of General Medical Sciences awarded Arkansas Children's Research Institute $107,307 on June 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) for a K99/R00 career development grant studying the mechanisms of muscle catabolism and hypermetabolism following burn injury and burn sepsis.

The award funds research into the underlying pathophysiological mechanisms driving muscle wasting, excessive metabolic stress, and impaired wound healing in burn injury complicated by sepsis. The investigator's stated objective is to develop improved animal models that fully replicate human burn pathophysiology—incorporating secondary sepsis, wound excision, skeletal muscle disuse atrophy, paired feeding protocols, and thermoneutral housing—to generate mechanistic insights that advance clinical outcomes in acute and chronic burn management. The K99/R00 mechanism provides mentored training to support the investigator's transition to independent research leadership.

Work is performed in Little Rock, Arkansas. The period of performance runs from June 1, 2026, through May 31, 2028. The funding is structured as a project grant, the assistance type for investigator-initiated research awards under NIGMS.

Abstract

My long-term career goal is to improve acute and chronic clinical outcomes in burn injury, sepsis, and burn sepsis. IT is well known that a majority of burn patients survive their initial trauma. However, complications often plague survivors for the remainder of their lives, greatly limiting their quality of life. These complications- namely muscle catabolism and hypermetabolism-are exacerbated by the development of sepsis, which serves as the leading complication of burn injury. Alarmingly, burn sepsis has exponentially greater mortality and morbidity rates than seen in either condition alone. Yet, limited research exists surrounding burn sepsis. The main objective of the K99/R00 award is to provide new mechanistic insight into the underlying mechanisms of burn sepsis hypermetabolism, catabolism, and wound healing while providing me with the critical mentored training i need to excel as an independent investigator to advance burn sepsis clinical outcomes. Our central hypothesis is that robust animal models that fully replicate clinical burns are essential in recapitulating the human pathophysiological response to burn trauma, where the accumulation of mitochondrial and oxidative damage drive a prolonged burn sepsis stress response that is marked by excessive hypermetabolism and catabolism, as well as impaired wound healing. Alarmingly, current rodent models largely fail at fully replicating human burn pathophysiology, and no model incorporates secondary sepsis, burn wound excision, disuse skeletal muscle atrophy, paired feeding between sham/burned animals, and thermoneutral housing to limit baseline cold-induced hypermetabolism. Our recent work indicates all these factors contribute to the failures of critical illness models and prevent scientific rigor and reproducibility. Indeed, only in validating animal models fully will we be able to gain mechanistic insight into the conditions they are designed to model. As such, this project will leverage top-down high-resolution phenotyping with ICU-like care to verify our animal models of burn injury with and without secondary sepsis fully recapitulate human pathophysiology. Due to the differences in mouse and human wound healing and immunology, we will also introduce a novel PIG model of burn sepsis. Through our PIG model, we will be able to quantify the contributions of skeletal muscle catabolism in wound healing, thereby furthering our findings in our optimized and fully validated mouse model of burn sepsis. In paring our basic findings with clinical data, we will gain significant insight into the mechanisms by which burn sepsis exacerbates the burn stress response. This work will be carried out under the direction of a team of basic researchers, physician scientists, and bioinformaticians to maximize rigor, reproducibility, and translatability of our findings. This project thus has value from a basic science standpoint in creating key tools to research the biochemical basic of acute burn trauma and its chronic complications, as well as from a clinical standpoint due to our proposed work in human patient samples.