# Functional Evaluation of CDH Patient Gene Variants in Vitro and in Select Animal Models

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $482,931

## Abstract

PROJECT III: FUNCTIONAL EVALUATION OF CDH PATIENT GENE VARIANTS IN VITRO AND IN 
SELECT ANIMAL MODELS 
ABSTRACT 
 Significant progress has been made in the care of Congenital Diaphragmatic Hernia (CDH) patients in the 
past two decades. Survival rates have been steadily improving, in part because of gentle ventilation 
techniques, high-frequency ventilation, cardiovascular pharmacologic support, and ECMO. 
 Currently, the main therapeutic goal is to stabilize the cardiac and respiratory systems in CDH infants, while 
attempting to minimize iatrogenic (therapy-induced) injury to the delicate pulmonary tissue, before undergoing 
surgical repair of the diaphragm. Lengthy stays in the neonatal intensive-care unit (NICU) are often necessary. 
Despite these successes, a large number of infants still succumb to the pulmonary complications of CDH, with 
late deaths mostly due to pulmonary hypertension and pulmonary insufficiency. 
 A major pulmonary defect associated with CDH is insufficient gas exchange, and pathology sections 
indicate that this is likely due to reduced number of alveolar septa. At the same time, a major contribution to 
lethality of infants with CDH is severe pulmonary hypertension due to abnormal vascular and vascular smooth 
muscle development, as well as failure of the vascular smooth muscle to relax normally after birth. 
 Using a complementary set of mammalian genetic, genomic, physiological, and three-dimensional 
morphological approaches, we propose to characterize in vitro and in vivo the pulmonary defects of CDH 
model organisms focusing on postnatal timing and cell types, including myofibroblasts and extracellular matrix 
constituents such as elastin. By identifying molecular mechanisms affected by different genetic mutations, we 
will design molecular assays that could eventually provide new paradigms for therapy, and reduce the 
economic, societal, and personal burden of CDH.

## Key facts

- **NIH application ID:** 9929455
- **Project number:** 5P01HD068250-09
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mauro Longoni
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $482,931
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929455

## Citation

> US National Institutes of Health, RePORTER application 9929455, Functional Evaluation of CDH Patient Gene Variants in Vitro and in Select Animal Models (5P01HD068250-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9929455. Licensed CC0.

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