# Sex as biological variable in Bronchopulmonary Dysplasia: Role of the Notch pathway

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2020 · $240,454

## Abstract

Bronchopulmonary dysplasia (BPD) is a debilitating lung disease with long-term
consequences and is one of the most common causes for morbidity in premature
neonates. Postnatal exposure to high concentrations of oxygen (hyperoxia) contributes
to the development of BPD. Despite the well-established sex-specific differences in the
incidence of BPD and impaired lung function in males, the molecular mechanism(s)
behind these are not completely understood. Our laboratory has been focused on the
study of sex-specific differences in neonatal hyperoxic lung injury. Aberrant Notch
signaling contributes to the pathogenesis of many chronic lung diseases and Notch
activation is seen in lungs of human infants with BPD. The role of aberrant Notch
signaling in pulmonary dysangiogenesis in BPD has not been determined. Critically,
neonatal female mice have improved alveolarization and pulmonary vascular
development, which is associated with, decreased Notch pathway activation and
expression of the Notch ligand Dll4 compared to male littermates in a murine model of
BPD. The overall aim of this innovative proposal is to define the role of sex-specific
activation of Notch pathway in modulating pulmonary angiogenesis in neonatal
hyperoxic lung injury. We hypothesize that decreased Notch activation secondary to
lesser Dll4 expression preserves pulmonary angiogenesis in female neonates . The
above hypothesis will be tested by the following specific aims: Aim 1: Elucidate the
spatio-temporal role of endothelial DLL4 (Notch ligand) in modulating pulmonary
angiogenesis. Aim 2: Determine the role pulmonary endothelial Notch signaling in
modulating pulmonary angiogenesis in the developing lung exposed to hyperoxia. This
proposal will address knowledge gaps in the molecular mechanisms behind the sexual
divergent incidence of bronchopulmonary dysplasia and lay the foundation for future
sex-specific treatment strategies.

## Key facts

- **NIH application ID:** 9874490
- **Project number:** 1R21HD100862-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Krithika Lingappan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,454
- **Award type:** 1
- **Project period:** 2020-06-23 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874490

## Citation

> US National Institutes of Health, RePORTER application 9874490, Sex as biological variable in Bronchopulmonary Dysplasia: Role of the Notch pathway (1R21HD100862-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874490. Licensed CC0.

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