Ke Yuan, Ph.D., received the 2019 PHA Aldrighetti Research Award for Young Investigators, with sponsorship support provided by Actelion Pharmaceuticals, U.S. The award, one of three Pulmonary Hypertension Association (PHA) research grants awarded last year, funds Yuan’s proposal, “SDF1 signaling: A Master Regulator of Mural Cell-Dependent Vascular Remodeling in PAH.” Yuan is an associate scientific researcher and member of the faculty of pediatrics at Harvard Medical School and a Parker B. Francis Fellow in the Division of Pulmonary Medicine at Boston Children’s Hospital. She previously was an instructor in the School of Medicine in the Division of Pulmonary Critical Care Medicine at Stanford University.
Here’s how she says her research could lead to improved patient outcomes:
“Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormally elevated pulmonary pressures and progressive right heart failure. If untreated, it can lead to death within a year of diagnosis. Current therapies include oral and intravenous agents with vasodilatory properties that improve symptoms but do not reverse or prevent the disease progression. That leaves lung transplantation, with its inherent high mortality and morbidity, as the only option for patients at the end stage. Thus, there is an unmet need for novel therapies capable of preventing progression and improving clinical outcomes in these patients.
“While the etiology of PAH is unknown, muscularized arterioles due to excessive pulmonary arterial smooth muscle cells (PASMCs) is a major pathological feature of this disorder. The source of PASMCs has been the subject of much speculation, and few studies have attempted to define the origin.
“We have found evidence that supports a key role for pericytes as a source of highly proliferating and contractile PASMCs in PAH. Studies proposed will provide novel insight into their role as a source of signaling cues that serve to ensure proper vessel regeneration and as novel targets for therapeutic interventions. This is an important goal because PAH remains an incurable disease that targets mostly middle-aged females and is associated with significant morbidity and loss of quality of life.
“By focusing on the mechanisms of vascular remodeling, we will discover novel approaches to prevent disease progression and facilitate regression of vascular pathology. Such strategies will significantly improve patient outcomes and potentially restore their capacity to breathe without considerable difficulty.”