Mohsin Khan, PhD, joins Sarver Heart Center to study how metabolism shapes heart repair
His lab's studies in mice ask why the adult heart stops regenerating, and whether that can be reversed.
Mohsin Khan, PhD, joined the University of Arizona Sarver Heart Center on Sept. 28 as an associate research professor in the Department of Cellular and Molecular Medicine at the College of Medicine – Tucson. He studies how the heart's metabolism affects its ability to repair itself after a heart attack.
A heart attack kills cardiomyocytes, the muscle cells that make the heart contract, and the adult heart essentially never replaces them. Scar tissue fills in, the surviving muscle works harder, and many patients develop heart failure. About 805,000 people in the U.S. have a heart attack each year, according to the Centers for Disease Control and Prevention. Newborn mice are different: for a short time after birth, their heart muscle cells can still divide. Khan's lab asks what shuts that ability down.
Researchers knew that the heart's metabolism, the way its cells make and use energy, shifts at about the time regeneration stops. They could not say whether the shift helps cause the loss. In a 2023 study in Circulation, Khan's team tested this with LIN28a, a protein that regulates metabolism and is active mainly while the heart develops. Mice engineered to keep producing it kept more of the small, single-nucleus heart muscle cells that can still divide than their unmodified littermates did. Twelve weeks after a heart attack, they had better heart function and survival. Blocking LIN28a with an inhibitor shrank the benefit, which points to the protein itself and not some other difference between the animals.
The result ties the heart's energy use to its ability to rebuild in mice. Whether raising LIN28a would be safe or work in people is unknown.
"What surprised me most was how much power one metabolic switch has over a heart cell's fate. Turning it back on not only added new myocytes, it improved survival," Khan said.
Khan comes to Tucson from Temple University's Lewis Katz School of Medicine, where he was an associate professor in the Department of Cardiovascular Sciences. His laboratory will be based on the sixth floor of the Sarver Heart Center.
His questions align closely with work underway at Sarver. Hesham Sadek, MD, PhD, has shown in mice that the newborn heart's switch to oxygen-rich, fat-burning metabolism helps halt heart muscle cell division. The lab of Luke Szweda, PhD, studies mitochondrial metabolism in heart disease.
"At Sarver, we want to find out whether resetting cardiomyocyte metabolism to a newborn state in adults can be done safely and precisely enough to become a therapy for people with heart failure, not just a laboratory finding," Khan said.