Jason Boehme, M.D., received the 2019 PHA Robyn J. Barst, M.D. Pediatric PH Research & Mentoring Grant in honor of Jackson Wall, one of three Pulmonary Hypertension Association (PHA) research grants awarded last year. An assistant professor of pediatrics at the University of California, San Francisco, Boehme is studying “Pulmonary Vascular Smooth Muscle Metabolic Reprogramming in Congenital Heart Disease.”

This is how Boehme says his research could lead to improved patient outcomes:

In children with congenital heart disease (CHD), exposure of the pulmonary arteries to abnormal hemodynamics initiates a biologic transformation of the vasculature. That ultimately leads to self-sustaining and progressive pulmonary arterial hypertension (PAH) refractory to surgical correction.

In advanced disease states, PAH stemming from CHD shares many biologic similarities with PAH from other etiologies and has similarly poor outcomes. This impact is particularly borne by children. In a recent pediatric study, more than a third of PAH cases were caused by congenital heart disease.

“Most research in the field is devoted to severe and advanced forms of PAH, leaving significant gaps in our understanding of disease progression, and early disease states in particular. We propose to study metabolic abnormalities in a unique ovine model of CHD, with vascular abnormalities that stem from an inciting physiology nearly identical to that found in children with CHD who progress to develop PAH.

“In our previous work, we identified a unique pattern of metabolic abnormalities in this model, distinct from those described in advanced disease states. This suggests that cellular metabolic changes in PAH differ based on underlying pathophysiology, phase of disease, or both. Importantly, this implies that metabolic therapies currently under evaluation for advanced PAH will fail in children with vascular dysfunction induced by pulmonary over circulation, due to differences in the underlying molecular mechanisms responsible.

“Our goal is to characterize the unique metabolic alterations, and the mechanical stimuli driving them, in a clinically relevant model of CHD in order to move toward more specific disease biomarkers and therapies for a clearly defined subset of pediatric patients.”