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Mentoring and Patient-Oriented Research in Human Neonatal and Infant Airway Biology

Award Number: K24HL177172
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Mentoring and Patient-Oriented Research in Human Neonatal and Infant Airway Biology - The goal of this application is to build a Patient-Oriented Research (POR) mentoring program in human neonatal and infant airway biology. This is a highly impactful research area, as severe viral respiratory infections remain the leading cause of death in newborns and infants. Furthermore, severe viral respiratory infections in early infancy increase the risk for lifelong respiratory morbidity, including asthma and COPD. Although improving respiratory outcomes during infancy is a top priority, the mechanisms regulating airway epithelial immune responses in early life are still largely unknown and understudied in humans. This research gap is even more significant for infants with trisomy 21 (TS21) and for those born severely premature, both historically excluded from respiratory research despite having the highest risk for severe respiratory infections. We have developed unique POR resources to address these gaps, studying the pathobiology of pediatric AECs during severe viral respiratory infections (HL141237), including TS21 (HL159595), and premature infants (HL145669). These resources have supported the training of over 40 mentees in this highly impactful research area. The proposed K24 research and mentoring plan will utilize these resources to build on our work that shifted the traditional view of newborns as completely immunosuppressed, into a new paradigm in which human neonatal AECs elicit strong IFN I-III responses to eliminate viruses at the point of entry and compensate for the immature adaptive immunity of early life. Using novel single-cell approaches, we recently expanded this notion, identifying that human AEC responses are mediated by a subset of antiviral IFN I-III-activated AECs, which are more abundant in newborns than in adults during viral infection. Our central hypothesis is that IFN I-III- activated AECs play a crucial role in mediating airway antiviral immunity in early life, and that premature birth and TS21 disrupt the balance of IFN activation, thereby altering the generation of these AECs and leading to increased severity during viral respiratory infections. The proposed POR will offer unique training opportunities for current and new trainees to conduct cellular, molecular, and clinical studies in human newborns and infants to investigate AEC dysfunction leading to severe viral infections, with a focus on high-risk groups. Our Specific Aim (SA) 1 is to define the impact of severe prematurity on IFN I-III–activated AEC development and its association with viral respiratory infection severity. SA2 will investigate the mechanism mediating altered IFN I-III AEC responses in severely premature infants and explore potential therapeutic approaches for this high- risk group. SA3 will define the mechanism and clinical implications of impaired IFN I-III AEC responses in infants with TS21 during viral respiratory infections. Together, the proposed K24 research and mentoring program will have a sustained high impact in the field by defining novel biological functions of the human neonatal and infant airway epithelium, while also identifying new targets and potential interventions to reduce the early onset and progression of respiratory diseases, consistent with the NHLBI Strategic Vision and Goals.


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 = $126,518 )
2026	2026	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Lung Diseases Research	000	1	8/3/2026	NEW	$126,518
														Subtotal = $126,518

Grand Total All Awards = $126,518

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Mentoring and Patient-Oriented Research in Human Neonatal and Infant Airway Biology

Award Number: K24HL177172

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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