Newborns with heart defects are born into a race against time. Their hearts, even if capable of pumping blood, are immature, still in the essential process of differentiating into specialized structures. It is this critical window that Dr. George Porter and his research team are trying to better understand. A pediatric cardiologist and researcher, Porter is leading efforts to uncover how mitochondria — cellular structures best known as the “powerhouses” of the cell — play a central role in guiding cardiac development. Positioned at the intersection of basic science and clinical care, the work of Porter’s lab could one day help vulnerable newborns win that race.
Porter always knew he wanted to go into pediatrics. His love for research, on the other hand, was more unexpected, stemming from an unplanned summer lab position as an undergraduate student that inspired him to pursue basic science alongside medicine. After earning a dual MD–PhD from the University of Maryland, Porter used his background in muscle cell biology to investigate heart development at Yale. It wasn’t until his move to Rochester, however, that he became more familiarized with the critical role of mitochondria in the developing heart. That spark set the stage for his current work: uncovering how mitochondria regulate cardiac development and drive the maturation of cardiomyocytes (which are the muscle cells responsible for the heart’s ability to contract and pump blood).
At the heart of Porter’s research is the mitochondria. Mainly thought of as producing energy for the body, mitochondria also play a pivotal role in guiding cardiomyocyte maturation. Interestingly, early in the neonatal period — which lasts four weeks after birth — these mitochondria are still immature, alongside the cells that they are located in. Porter’s team has shown that as mitochondria mature, they help drive the transition of cardiomyocytes from rapidly dividing, unspecialized cells to fully functionally specialized cardiac muscle cells. Though the team is interested in understanding the entire span of cardiac development, the lab has shifted its priority to after the baby is born, where clinical intervention becomes a possibility. Porter noted how the 4-week neonatal window offers both a critical phase of development and a rare opportunity for potential therapies to make a difference in real time.
To understand how mitochondria influence cardiac development, Porter’s lab has turned its focus to the mitochondrial permeability transition pore (mPTP). The mPTP is a channel regulated primarily by a mitochondrial protein known as Cyclophilin D (CypD). Prolonged opening of mPTPs is typically associated with mitochondrial dysfunction and cell death, and Porter’s lab has shown that the closure of these mitochondrial pores during embryonic development is what drives mitochondrial maturation and subsequent cardiomyocyte differentiation. This shift marks a transition from proliferation (rapid cell division) to differentiation (specialization). As Porter puts it, “you need to make more cells, but at some point those cells have to form mature cells.” More recent investigations from Porter’s team has demonstrated that the same phenomena occurs in neonatal hearts — where the closure of the mPTP improves mitochondrial function and enhances cardiac performance.
This novel understanding of mitochondrial involvement in cardiac development carries significant clinical promise, but its translation into practice relies on whether these insights can be safely and effectively applied in the neonatal setting. Two drugs of particular interest to Porter — cyclosporin A and NIM811 — promote the closure of the mPTP and encourage cardiomyocyte differentiation by inhibiting the mitochondrial protein Cyclophilin D.
More differentiated cells produce more cellular energy and have greater strength to contract and pump blood. This shift could help neonatal hearts rapidly mature to meet postnatal circulatory needs, especially in newborns with congenital heart defects. However, this shift towards maturation comes at the cost of proliferation, potentially limiting the total number of cardiomyocytes formed during a critical developmental window.
Despite this tradeoff, Porter believes the benefits could outweigh the costs in critical care scenarios. “If you can get the kid through that neonatal period,” he explained, “not just by giving them drugs that cause the heart to squeeze better, but by actually changing the trajectory of the cells that are there? That would be good.” Supporting early maturation, he suggests, could stabilize these fragile hearts to get them through their sickest stretches. As for the long-term consequences of reduced proliferation, Porter stated that it “can be dealt with later.”
Despite its promise, translating this research into treatment remains complex. Cyclosporin A, while promoting cardiomyocyte maturation, has historically been used as an immunosuppressant, posing serious health risks for already vulnerable newborns. Even non-immunosuppressive alternatives require extensive testing for safety and efficacy in neonatal contexts. Still, if a targeted therapy could safely accelerate heart maturation in the days following birth, it could change outcomes for infants with congenital heart disease, helping fragile hearts stabilize not just through surgical repair, but through cellular resilience.
Understanding how mitochondria govern the heart’s transition from fetal to postnatal life offers more than just insight — it opens doors. For Porter, the next five to 10 years are about translating this bench research to safe, targeted therapies that can guide developing hearts toward function when it matters most. His hope is simple but bold: to give fragile newborns not just a chance at survival, but a stronger start. If successful, the research Porter’s lab is pioneering could change the outcomes for the tiniest hearts facing the biggest odds.
