Rachel Bentley

2022 Paroian Family PH Research Scholarship

Department of Medicine, Queens University 

Under the supervision of: Dr. Stephen L. Archer

About Rachel Bentley

Rachel Bentley is a second-year Ph.D. candidate in the Translational Medicine graduate program at Queen's University (Kingston, ON) following her successful promotion from her Master’s to Ph.D. in 2021. She obtained a Bachelor of Sciences in Life Sciences at Queen's University in 2019. She is currently studying the oxygen-sensing mechanisms of the ductus arteriosus and pulmonary arteries in a search for novel therapeutic pathways for persistent pulmonary hypertension of the newborn (PPHN).

Project:

Why do two key fetal blood vessels, the ductus arteriosus and the pulmonary arteries, have opposite responses to the rise in blood oxygen that occurs with the newborn’s first breath?

Before birth, blood flow to fetal lungs is low since the placenta provides oxygen (O2). The ductus arteriosus (DA), an artery connecting the pulmonary artery (PA) and aorta, allows blood to bypass the unventilated lungs. With the first breath, O2 rises, simultaneously causing DA constriction, which diverts blood to the lungs, and pulmonary artery (PA) relaxation, which accommodates increased blood flow and gas exchange. The mechanism for the opposing O2 responses of fetal PA and DA is unknown. Failure of this O2-sensing contributes to two congenital heart diseases, especially in premature infants: persistent ductus arteriosus (PDA) and persistent pulmonary hypertension of the newborn (PPHN).

We have established that 1) core mechanisms of O2-induced DA constriction and PA dilation reside in the mitochondria of vascular cells. Mitochondria serve as O2 sensors and produce signalling molecules that regulate blood vessel tone. 2) In adult arteries with opposing O2 responses, we discovered spatial differences in the composition and function of mitochondrial sensor subunits. Here we investigate the identity of the fetal O2 sensors and assess whether differences in mitochondrial structure and function between the DA and PA underly their opposing responses. This research will identify new treatments for PDA and PPHN.