Brooke O’Donnell, PhD, a postdoc mentored by Brant Isakson, PhD, was awarded a postdoctoral research fellowship from the American Heart Association. Her project, “PANX1 Y198 Phosphorylation Promotes the Development of Hypertension,” investigates how a particular chemical change to the Pannexin 1 protein can affect blood pressure.
High blood pressure is common in the United States, and approximately 20% of cases are resistant to currently available treatments. Blood pressure is partly controlled by the muscle cells lining most blood vessels, so identifying components of these cells that modulate blood pressure is a valuable pathway to developing new treatments. O’Donnell is an expert in one such component, Pannexin 1. Pannexin 1 is a channel protein responsible for transporting small molecules and ions across the cell membrane. O’Donnell and Isakson have found that phosphorylation of a single Pannexin 1 amino acid, tyrosine 198, is overrepresented in patients with high blood pressure. Using a peptide to target this amino acid can visibly relax medication-resistant blood vessels, indicating the importance of tyrosine 198 phosphorylation of Pannexin 1 in blood pressure control. “The point of my project is to figure out the mechanism of how this molecular alteration can translate to changes at the organism level in normal blood pressure homeostasis, then understand how it contributes to the initiation and progression of hypertension,” explains O’Donnell. The work that the fellowship funds will target these goals and also compare the Isakson lab’s peptide treatment against current standards of care. “My main goal is to support patients and figure out how to make better treatments,” she said.
A trained cell biologist with experience studying Pannexin 1 in cancer, O’Donnell joined the Isakson lab to bring her expertise in molecular biology to the team and develop as a cardiovascular scientist. “I’ve seen family and friends affected by cardiovascular disease, and it’s been a personal goal of mine to study the vasculature and hypertension,” she said. “Working with Brant was a really exciting opportunity. We initially met in 2019 at a Pannexin conference while I was a Master’s student. He immediately asked if I could come to Charlottesville. Five years later, I did,” O’Donnell recollected. “Brant and my labmates have fully supported me and my research. They’ve been instrumental in my training at UVA and I’m really appreciative of their help.”