Collaborative project seeks safer therapies for ischemia and reperfusion injury

Southwest Research Institute (SwRI) and Trinity University will improve a prodrug, a compound activated in the body, to mitigate tissue and organ damage associated with heart attacks, strokes and traumatic injuries. These conditions cause a lack of blood flow, but treatment to reverse blockages can also lead to lasting damage.

A project collaboratively funded by SwRI and Trinity will address both the initial lack of blood (ischemia) and the rush of blood that follows treatment (reperfusion) referred to as ischemia/reperfusion injury (IRI).

"The moment oxygen comes flooding back into your cells during reperfusion, the surrounding tissue is inundated with reactive oxygen species, such as hydroxyl radicals and hydrogen peroxide. That oxidative stress can cause permanent cellular and tissue damage," said Dr. Christina Cooley, associate professor with the Department of Chemistry at Trinity University.

Cooley discovered AA 147, a compound that activates specialized proteins to protect against reactive oxygen species and ensure a healthy protein response.

SwRI will work with Trinity to iterate and synthesize a new borinic acid prodrug to prevent IRI using precursors developed at Trinity. Unlike traditional pharmaceuticals, prodrugs are biologically inert until they are converted inside the body into an active therapeutic compound.

"Protein misfolding during cellular stress is a key driver of tissue damage in IRI, so the new prodrug will target that," said Dr. Christopher Dorsey, a senior research scientist at SwRI who will use his pharmaceutical expertise to synthesize the new borinic formulation. "Once we figure out the synthesis route, we will train Trinity students to carry out our new technique. That's the exciting part of this collaboration, the opportunity to give back and pass along what we learn to a team of future scientists."

The SwRI and Trinity researchers will work together to improve release mechanisms for the latest prodrug iteration that will maximize its therapeutic effect with the goal of protecting patients at risk for IRI. After the prodrug is synthesized, Cooley will work with Trinity students to conduct stability testing and other lab evaluations to gather the foundational data needed for future live studies and clinical trials.

This project was funded through the inaugural Trinity-SwRI Research Collaboration Grant Program established in 2025 to encourage the advancement of medical and biomedical research through collaboration. Trinity University and SwRI contributed $250,000 toward three unique biomedical research projects this year.

"Trinity University is thrilled to be collaborating with SwRI, and we look forward to exciting results from this collaboration," said Dr. David Ribble, dean of the D. R. Semmes School of Science.

We are proud to launch this new focused grant program to grow Trinity and SwRI collaborations, provide opportunities for Trinity students and advance medical breakthroughs that may one day improve and even save lives."

Dr. Joe McDonough, vice president of the Chemistry and Chemical Engineering Division, SwRI