# Using Induced Pluripotent Stem Cells to Characterize Cystic Fibrosis

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2021 · $167,940

## Abstract

Project Summary/Abstract
This proposal details a 5-yr plan to prepare the candidate, Ruobing Wang, MD, for a career as an independent
physician-scientist positioned to impact our understanding of pediatric lung diseases, particularly Cystic
Fibrosis (CF). As a clinician taking care of CF patients, she has identified rare individuals with homozygous
F508del CFTR mutations who met clinical criteria for inclusion as: 1) CF Long-term non-progressors (LTNP),
with preserved lung function 2) CF Rapid progressors (RP), whose lung function declines rapidly. Whole exome
sequencing uncovered rare missense polymorphisms in i) SCNN1 (which encodes epithelial sodium channel
ENaC) in LTNPs, and ii) two genes in epithelial alternative chloride channels (ANO1 and SCL26A9) in RPs. The
central hypothesis of the proposal is that the extreme phenotypes of CF are due to the alterations in
epithelial ion and fluid transport driven by these gene defects, and that the extreme-phenotype disease
severity and mechanism can be modeled and studied in vitro with a reprogrammed cell-based platform. Using
a novel protocol, Dr. Wang generated airway basal-like cells from induced pluripotent stem cells (iPSCs) which
can then differentiate into basal, multi-ciliated, and secretory lineages on air-liquid interface, forming a functioning
airway epithelium with intact barrier function and aberrant trans-epithelial chloride transport. Normalization of
chloride transport in these cells by CFTR gene editing confirms the reliability of her model to recapitulate CF
phenotype. The central goals of the project are to establish this novel iPSC-platform for CF disease modeling
and study the epithelial function of the extreme-phenotype patients. She is now uniquely poised to complete
the aims to 1) To test whether iPSC-derived airway epithelia can serve as a platform to model airway
epithelial ion and fluid transport and muco-ciliary transport in CF, 2) to model extreme-phenotype CF patient
and interrogate the role of candidate modifier genes and their impact on ion and fluid transport, and 3) To
establish the iPSC-platform for personalized drug response, and test the therapeutic role of pharmacologic
targeting of alternative ion channel candidates. Dr. Wang has 80% protected time from Boston Children's
Hospital (BCH) Division of Respiratory Diseases and the Department of Medicine. Her co-sponsors are 1) Dr.
Darrell Kotton at the Center for Regenerative Medicine (CReM) at Boston University (BU) with whom she has
trained for the past 1.5 years, and 2) Dr. Benjamin Raby, the chief of BCH Division of Respiratory Diseases.
Furthermore, Dr. Wang has assembled a team of extraordinary scientific advisory members, each bringing
their specific expertise, to assist her career development and scientific research. A detailed training plan is
presented that includes mentored research, didactic coursework, presentations at meetings, and a timeline for
completion of the research aims, preparation of manuscrip...

## Key facts

- **NIH application ID:** 10106123
- **Project number:** 1K08HL155892-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Ruobing Wang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,940
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106123

## Citation

> US National Institutes of Health, RePORTER application 10106123, Using Induced Pluripotent Stem Cells to Characterize Cystic Fibrosis (1K08HL155892-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10106123. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*