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Modeling the Airway Epithelial Microenvironment in Asthma at Single Cell Resolution

Award Number: K23HL183783
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Modeling the Airway Epithelial Microenvironment in Asthma at Single Cell Resolution - PROJECT SUMMARY Ryan Murphy, MD plans for a career as a physician-scientist in human translational asthma research. Support from this K23 award will provide necessary training in development of patient cohorts, statistical approaches, advanced cell culture techniques, and analytical methods for the analysis of single cell and spatial transcriptomic datasets. The training plan described will complement Dr. Murphy’s basic and translational research background & facilitate his transition to independent research. The proposal leverages Dr. Murphy’s unique access to mentors in asthma, systems biology, and epithelial and mast cell biology as well as core facilities and resources within the Seattle Asthma & Allergic Diseases Cooperative Research Center (AADCRC). The proposal focuses on communication between mast cells (MCs) and airway epithelial cells (AECs) as a critical contributor to treatment-refractory airway inflammation in asthma. There have been significant advancements in our understanding of the inflammatory mechanisms responsible for asthma pathogenesis (including dichotomizing individuals into two endotypes based on the presence or absence of type 2 (T2) biomarkers), but 3-10% of individuals with asthma have uncontrolled disease despite application of current therapeutics. Thus, there is an urgent need to identify cell-specific treatment-refractory inflammatory mechanisms. Dr. Murphy’s preliminary data and published work indicates that MCs that uniquely infiltrate the airway epithelial compartment in asthma (“intraepithelial MCs”, MCIE) are a key source of corticosteroid-resistant inflammation, and are regulated by interactions with AECs. This proposal leverages Dr. Murphy’s expertise in advanced cell culture techniques as well as the existing infrastructure within the Seattle AADCRC to enhance and enrich a novel biorepository of adult AEC donors to study crosstalk between MCs and AECs using a novel ex vivo model system with asthma phenotype- and endotype-specific resolution. In this patient-oriented research plan, Dr. Murphy will use these resources to address his hypothesis that MCIE are key sources of corticosteroid-refractory inflammation in asthma, and are differentially regulated by AECs obtained from healthy individuals versus those with T2-high or non-T2 asthma. Dr. Murphy will address this hypothesis using single cell RNA-sequencing (scRNAseq) and spatial transcriptomics to: (1) characterize transcriptional differences in AECs based on asthma phenotype & endotype, (2) examine the mechanisms that regulate AEC-MC crosstalk, and (3) identify corticosteroid-resistant mechanisms of inflammation in the asthmatic airway epithelial microenvironment. The results of these studies will significantly enhance our understanding of MCIE in specific asthma endotypes, which may identify novel regulatory mechanisms and therapeutic targets for individuals with treatment-refractory asthma. This K23 award will provide Dr. Murphy the necessary training in systems biology skills, development of human translational research cohorts, and his own unique adult asthma AEC biorepository that will be the foundation for an R01 application and his independent research career.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $188,892 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Lung Diseases Research	000	1	8/10/2026	NEW	$188,892
														Subtotal = $188,892

Grand Total All Awards = $188,892

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Modeling the Airway Epithelial Microenvironment in Asthma at Single Cell Resolution

Award Number: K23HL183783

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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