By: Ada Chong
August 2023
Jennifer Kwong studied cell biology as an undergraduate, neuroscience during her PhD, and cardiac biology in her postdoc. Her lab investigates research questions stemming from interests developed from her doctoral work at Cornell on mitochondria dysfunction and how energy dysfunction contributes to neurogenerative diseases, combined with her postdoctoral training at Cincinnati Children’s Medical Center on cardiac disease. Currently, her team studies the heart’s use of energy, how mitochondria contribute to heart failure, as well as how energy systems contribute to heart development.
Dr. Kwong started her research on single ventricle defects after Victor Faundez, MD, PhD, (Department of Cell Biology) reached out to her about collaborating on studying mitochondrial dysfunction in 22q11.2 Deletion Syndrome. This research was aimed at identifying what genes are deleted within 22q11.2 chromosomal region that underlie the neuropsychiatric defects associated with the disorder. This collaborative work identified the mitochondrial citrate carrier to be a deleted gene central to the neuropathology of the syndrome. As 22q11.2 Deletion Syndrome, also known as DiGeorge Syndrome, is a major risk factor for congenital heart defects, Dr. Kwong is now studying the impact of loss of the mitochondrial citrate carrier in heart. Analyzing embryos from a mouse model of citrate carrier deletion to look at the impact of gene deletion on heart physiology, mitochondrial structure, and cellular metabolism, Dr. Kwong’s group found that loss of the mitochondrial citrate carrier gene causes lethality of embryos. Importantly, her group found that partial loss of this gene is sufficient to produce congenital heart defects, including some of the heart defects observed in 22q11.2 Deletion Syndrome and Single Ventricle Disease patients. Importantly, to extend the clinical relevance of this work, Dr. Kwong’s research shows that there is a near-significant association of ultrarare genetic variants of the mitochondrial citrate carrier gene with pediatric congenital heart disease.
Dr. Kwong’s top goals for her research include understanding how mutations in the mitochondrial proteins, including the mitochondrial citrate carrier, impact the structural development of the heart, and expanding the network of genes that cause congenital heart disease. Can information gained from this research on the mitochondrial citrate carrier be used to reduce incidents of congenial heart defects? Dr. Kwong hopes that understanding the basic biology of how mitochondrial energy systems impact heart development will form the foundations for future clinical developments to prevent and treat congenital heart disease.