# Novel NOTCH4 Pathway of Asthma Severity in Urban School Children: Clinical Research Center, Boston Children’s Hospital

> **NIH NIH U01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $506,000

## Abstract

PROJECT SUMMARY
This CAUSE application brings together seasoned clinical and laboratory investigators in inner-city asthma, with
expertise in clinical studies and clinical trials, immunology, genetics, environmental exposures, bioinformatics,
data management, and statistics. The investigators have long track records in implementing multi-center and
single-center clinical trials and observational studies in allergic diseases, including asthma, to the standards of
NIH funded clinical research networks, in conducting NIH fundamental research on disease mechanisms in
asthma and in training generations of investigators in asthma research
In part A we demonstrate that we have the personnel and facilities to conduct asthma network-wide and Clinical
Research center-specific research on inner-city children with asthma populations recruited from the allergy and
asthma clinics at Boston Children's Hospital and from our just completed, as well as ongoing, NIH-funded studies
of inner-city schoolchildren with asthma, allergic diseases and healthy controls. We have a highly experienced
team, IRB-approved protocols for recruitment and clinical characterization of asthma patients and healthy
controls and an infrastructure which includes clinical research facilities, investigational pharmacy services, a
laboratory facility capable of processing, storing and shipping human samples, a state-of-the-art immunology
research laboratory with a 25 year focus on asthma and a data management facility with quality control plans,
and capability to upload data into the NIAID designated repositories and biostatistical support.
In part B our Center specific project draws from previous work on the novel NOTCH4 pathway and airway
inflammation and will draw on an already well-characterized urban school population of asthma patients and
healthy controls. Our overall hypothesis is that NOTCH4 signaling acts to regulate airway inflammation and
increases asthma severity and loss of control in inner-city school children. Our aims are to 1) test the hypothesis
that elevated peripheral blood NOTCH4+ Tregs defines a population of patients whose asthma is driven by an
IL-6 dependent mechanism that confers a more severe or poorly controlled phenotype 2) determine the
environmental determinants of the NOTCH4+ Tregs and how they mediate disease severity and control and 3)
investigate whether regulatory variants that increase NOTCH4 protein expression are associated with more
severe asthma phenotypes and endotypes.
This project will confirm the role of environmental exposures we have found important in urban schools and
homes of children with asthma and that regulatory variants that impact signaling may be modified by novel
mechanistic gene by environment pathways. We will elucidate novel mechanisms fundamental to the biology of
airway inflammation and pave the way for future biomarker driven approaches to inform future precision therapy.
We address a critical knowledge gap in reducing dispropo...

## Key facts

- **NIH application ID:** 10840786
- **Project number:** 5U01AI160087-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Talal Amine Chatila
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $506,000
- **Award type:** 5
- **Project period:** 2021-04-13 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840786

## Citation

> US National Institutes of Health, RePORTER application 10840786, Novel NOTCH4 Pathway of Asthma Severity in Urban School Children: Clinical Research Center, Boston Children’s Hospital (5U01AI160087-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840786. Licensed CC0.

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