William Oldham, M.D., Ph.D.
Research Awards Nationwide Recipient (2016-2017)
Brigham and Women's Hospital
Funded by the American Lung Association of the Northeast
"Metabolic Map" May Identify Pathways to Target in Pulmonary Arterial Hypertension
Abnormal growth of pulmonary vascular cells causes narrowing of blood vessels in the lungs, leading to pulmonary arterial hypertension (PAH) and heart failure. Accumulating evidence indicates that PAH is associated with marked changes in cell metabolism in the pulmonary blood vessels. Having a better understanding of metabolic changes in models of PAH may enable us to develop new, targeted therapies. We will create a "metabolic map" that traces the flow of carbon atoms from food sources (like glucose) through cellular metabolic pathways in diseased lung vessels. With this metabolic map, we will be able to identify the pathways that are important for supporting the abnormal cell growth that is critical to drive PAH.
Update: Over the past year, we have defined the optimal growth conditions for normal pulmonary artery smooth muscle cells (PASMCs) to ensure cells are at metabolic steady state at the time of labeling. We have treated these PASMCs with glucose and the amino acid glutamine and traced the distribution of these food sources through cellular metabolic pathways. We are using these data to develop a mathematical model of PASMC metabolism. We have also obtained PASMCs from patients with pulmonary arterial hypertension and are preparing to perform labeling of these cells.
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