Dr. Robyn J. Barst Pediatric PH Research and Mentoring Fund Grant Winner 2016

Rachel Hopper, MDRachel Hopper, MD

Attending Physician
The Children’s Hospital of Philadelphia
Title: “Comprehensive Analysis of Persistent Pulmonary Hypertension in Congenital Diaphragmatic Hernia”
Term: December 1, 2016 – November 30, 2016

Summary of Research Project:

Congenital diaphragmatic hernia (CDH) is one of the most common birth defects, affecting about one in 3,000 infants. Due to a defect in formation of the diaphragm in fetal life, abdominal organs migrate into the chest, compress the growing lungs and negatively impact lung development. There is a spectrum of severity, related to size of the defect and the degree that the developing lungs are affected. After birth, babies with CDH can develop pulmonary hypertension (PH), which can lead to right heart failure. PH resolves in most infants but remains in a subset of patients. Persistent PH is associated with increased risk of death in infants with CDH. Long-term outcomes and specific risk factors for persistent PH in CDH remain poorly understood. PH was originally thought to be purely associated with lung size, due to a smaller number of blood vessels in under-developed lungs. However, while babies with smaller lungs are at higher risk for PH, some with larger lungs can still develop PH. We think these babies may have other abnormalities of their blood vessels, similar to those seen in patients with other types of PH. This may be due to a genetic variation, related to CDH, which confers a predisposition to PH. The goal of this project is to study our cohort of over 300 patients with CDH to study both clinical and genetic factors that may contribute to PH in CDH. We will analyze our cohort to determine how many patients have persistent PH at 6 months of age, suggesting underlying abnormalities of the pulmonary blood vessels. We will investigate fetal and neonatal clinical factors are associated with persistent PH, which could include variables related to CDH anatomy, additional medical conditions, surgical repair or treatments. We will use advanced genetic sequencing technology to screen a subset of infants for gene mutations that may predispose to PH. Comparing to children with CDH and no PH will tell us if there are other gene mutations independent of those potentially causing CDH that may explain this clinical spectrum of disease. We hope this study will improve understanding of PH in CDH and thereby increase our ability to predict and treat this significant cause of morbidity and mortality in children with CDH.

Curriculum Vitae

Education/Training

1997-2001 BA, Pomona College (Molecular Biology)
2001-2007 MD, University of Michigan Medical School (cum laude)
2007-2008 Intern in Pediatrics, Children’s Hospital Boston (Boston Combined Residency Program in Pediatrics)
2008-2010 Resident in Pediatrics, Children’s Hospital Boston (Boston Combined Residency Program in Pediatrics)
2010-2013 Fellow in Pediatric Cardiology, Lucile Packard Children’s Hospital at Stanford University
2013-2014 Senior Clinical Fellow in Pulmonary Hypertension, Lucile Packard Children’s Hospital at Stanford University

Honors/Awards

2002 Amgen Medical Student Research Award, University of Michigan Medical School
2003-2005 Howard Hughes Medical Institute NIH Research Scholars Program
2005 Continued Fellowship for Medical Studies Scholarship Award, Howard Hughes Medical Institute
2007 Dean’s Award for Research Excellence, University of Michigan Medical School
2011-2014 Stanford Society of Physician Scholars
2012 Research Award, Child Health Research Institute, Lucile Packard Children’s Hospital at Stanford

Research Support

1U01HL121518-01 PI: Abman 7/1/2014-4/30/2018
Data Fusion: A sustainable, scalable, open source registry advancing pulmonary vascular disease research
Source: NHLBI/NIH
Role: Co-investigator (site PI)
Goal: create a large registry of pediatric pulmonary hypertension patients in North America and patients are actively being enrolled at this time.

United Therapeutics Grant PI: Mercer-Rosa/Hopper 12/9/2015-12/8/2020
Investigator initiated study to investigate the effect of prostacyclin therapy on the right ventricle.
Role: Co-investigator (co-PI)
Goal: to evaluate clinical and echocardiographic parameters of right ventricular function retrospectively in pediatric pulmonary hypertension patients treated with prostacyclin therapy.

CHOP Cardiac Center Grant PI: Hopper 7/1/16-6/30/17
Use of Patient Derived Multi-potent Cardiopulmonary Stem Cells to Study Mechanisms of Pulmonary Vein Stenosis.
Role: PI
Goal: is to use patient-derived stem cells to study developmental abnormalities that may contribute to the development of pulmonary vein stenosis in infants and children.

Selected Publications

  1. Hopper RK, Moonen JA, Diebold I, Cao A, Rhodes CJ, Tojais NF, Hennigs JK, Gu M, Want L, Rabinovitch M. (2016) In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and its Target Slug. Circulation 133(18):1783-94 PMID: 27045138.
  2. Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El-Bizri N, Sawada H, Haghighat R, Chan R, Haghighat L, de Jesus Perez V, Wang L, Reddy S, Zhao M, Bernstein D, Solow-Cordero DE, Beachy PA, Wandless TJ, Ten Dijke P, Rabinovitch M. (2013) FK506 Activates BMPR2, Rescues Endothelial Dysfunction, and Reverses Pulmonary Hypertension. J Clin Invest 123(8):3600-3613. PMID: 23867624.
  3. Hopper RK, Feinstein JA, Manning MA, Benitz W, Hudgins L. Neonatal Pulmonary Arterial Hypertension and Noonan syndrome: two fatal cases with a RAF1 mutation. (2015) Am J Med Genet. Part A 167A(4):882-5. PMID: 25706034.