Making heart scar tissue a nonissue

Ahmed Mahmoud, PhD, planned to complete his doctoral degree and enter the pharmaceutical industry to help teams develop new therapies.   

“My goal then was to study the research and development process, to see how drugs are formed and all the steps that eventually lead to therapeutics,” said Mahmoud, who joined Sanford Burnham Prebys as an associate professor in the Center for Cardiovascular and Muscular Diseases on February 28, 2025.

“Once I got into the laboratory, however, I became fascinated by regenerative biology.”

Mahmoud was especially interested in the heart as damage to tissue and cells from heart attacks and chronic heart disease leaves permanent scars. Broken bones mend and split skin knits itself together, but damage to hearts only compounds and weakens cardiac muscle.

“Once you have a heart attack, a piece of your heart muscle dies, and it goes away,” said Mahmoud. “Despite scientists’ best efforts, it has been a pretty irreversible process.” Heart disease is the leading cause of death in the U.S. and around the world, and someone in the U.S. has a heart attack approximately every 40 seconds.

During his PhD studies, Mahmoud conducted research in a lab at the University of Texas Southwestern in Dallas that found that the heart has more regenerative capabilities than previously thought.

“We didn’t know before then that neonatal mammalian hearts regenerate, and part of my work in graduate school led to that discovery in mice,” said Mahmoud. “Of course, that begged the question of whether or not we could use that finding to reprogram adult hearts to regenerate.”

Following a postdoctoral fellowship at Harvard University, Mahmoud started his independent laboratory at the University of Wisconsin-Madison in 2017. His team focused on how to repair adult mouse hearts by restoring the regenerative powers they had once possessed.

“We found that we can turn on the same mechanisms by tweaking the metabolic state of the adult heart,” said Mahmoud. To test this, his team induced adult mice to have heart attacks, then treated them with a metabolic inhibitor designed to reprogram the metabolism of heart cells back into a neonatal state.

“We found that these hearts later looked completely normal, like uninjured hearts,” said Mahmoud. “It was astonishing, so we tried it over and over to make sure we could believe what we were seeing.

“What had started years earlier with finding the natural regeneration that occurs in neonates had culminated in something we could replicate in adult mice, so that was definitely the highlight of my career so far.”

Now, Mahmoud wants to advance this discovery even further by using it to develop treatments that may one day benefit patients. He feels that the environment at Sanford Burnham Prebys will help him accomplish his goals.

“I think the collaboration across disciplines that is fostered at the institute will be very helpful, as will the drug discovery expertise at the Conrad Prebys Center for Chemical Genomics,” said Mahmoud.

“I work at the intersection of both making basic science discoveries and transforming them into actual therapies to improve health. Bridging that gap is the hallmark of what happens at Sanford Burnham Prebys and why I’m excited to advance my research here.”