The majority of people who die after trauma do so because of multiple organ failure, resulting from an over-active immune system that attacks the vital organs. While multiple therapeutics aimed at toning down the inflammatory response have been successful in animal models, none have been successful in the clinical setting. Understanding what makes the human response to injury and inflammation unique from other species is integral to developing clinically applicable therapeutics.
Trauma Research Fellow Dr. Theresa Chan, together with Drs. Todd Costantini, Andrew Baird, and Brian Eliceiri, are studying the effects on the systemic inflammatory response of a gene present only in humans known as CHRFAM7A. With support from the NIH and Shock Society, they created the first CHRFAM7A transgenic mice. With this one human gene inserted into a mouse genome, they can pin point specific functions are related to CHRFAM7A alone. Thus, the team are able to study how CHRFAM7A changes the systemic inflammatory response, namely by measuring changes in the immune cell response in the bone marrow after injury and tracking these changes to organs including the lung and spleen.
By inserting this uniquely human gene into a mouse, the research team will be able to answer important questions related to the function of CHRFAM7A. Not only is it possible for this gene to change the amount of immune cells released as part of the systemic inflammatory response, it may also alter the function of these cells. This may allow researchers to understand why some patients exhibit an overwhelming systemic inflammatory response that alters their outcome after trauma, while other patients do not; and why drugs that have worked in animal models have not translated to clinically applicable therapeutics.
The bottom line: CHRFAM7A plays a key role in modulating the human response to inflammation. Inserting this uniquely human gene into mice allows the research team to establish clear biological consequences of CHRFAM7A expression and characterize changes in immune cell function after injury.
Theresa Chan is a Trauma Research Fellow; Todd Costantini is Associate Professor of Surgery and Director of the Trauma Center; Andrew Baird is Vice Chair for Research and Professor; and Brian Elicieri is a Professor and Principal Investigator, Elicieri Lab—all in the Division of Trauma, Surgical Critical Care, Burns & Acute Care Surgery.
Dr. Theresa Chan
Dr. Todd Costantini
Dr. Andrew Baird
Dr. Brian Eliceiri