Researchers at Children’s and UAB are exploring how mitochondrial function may help predict BPD risk.
Bronchopulmonary dysplasia (BPD), a chronic lung condition affecting some extremely preterm infants, continues to be a significant clinical challenge in neonatology. While often lifesaving, supplemental oxygen can be a key contributor to long-term pulmonary complications in this vulnerable population. At Children’s of Alabama and the University of Alabama at Birmingham (UAB), researchers are exploring how mitochondrial function may hold the key to understanding and preventing BPD.
Jegen Kandasamy, M.D., an associate professor in the Division of Neonatology at UAB, leads a multidisciplinary team supported by a research grant dedicated to studying mitochondrial dysfunction in BPD. The research centers on individual differences in how mitochondrial DNA (mtDNA) haplogroups—genetic variations inherited maternally and varying by ethnicity—may influence an infant’s susceptibility to lung injury from oxygen exposure, particularly hyperoxia.
“Hyperoxia is a double-edged sword,” Kandasamy said. “It’s essential for survival, yet it introduces oxidative stress that preterm lungs are poorly equipped to handle. Our research is aimed at understanding how mitochondrial genetics impact that response.”
Using collected blood samples and clinical data from preterm infants, Kandasamy’s team is working to identify mtDNA haplogroups associated with higher BPD risk. The goal is to develop precise, genetically informed risk profiles that allow for early intervention. Hopefully, this will improve outcomes while addressing racial disparities in BPD prevalence and severity.
An especially promising area of research is platelet bioenergetics. By measuring how platelets utilize mitochondrial energy, the researchers hope to identify specific biomarkers that reflect systemic mitochondrial health and may help predict BPD risk. “Platelets are easy to access and give us a real-time snapshot of mitochondrial function without invasive procedures,” Kandasamy noted.
The team is also studying mitophagy, the elimination of damaged mitochondria through autophagy, and its role in lung development. Emerging evidence suggests that impaired mitophagy contributes to persistent mitochondrial dysfunction, exacerbating lung injury in preterm infants. As a result of this new evidence, the group is also evaluating the potential of thyroid hormone supplementation as a therapeutic strategy to restore mitochondrial function and mitigate lung damage.
By integrating clinical data with mouse models, the UAB team is uniquely positioned to investigate both the mechanistic underpinnings of BPD and potential interventions. The collaborative effort spans neonatology, mitochondrial biology and pediatric pulmonology, creating a comprehensive research environment.
“Our ultimate aim is to shift the paradigm from reactive to predictive personalized neonatal care,” Kandasamy said. “Understanding how mitochondrial genetics intersect with environmental exposures can help us identify at-risk infants earlier and intervene more effectively.”