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Interstitial macrophages in cigarette smoke-induced small airway remodeling

Award Number: K08HL155894
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Interstitial macrophages in cigarette smoke-induced small airway remodeling - PROJECT SUMMARY Project Summary: This proposal describes a 5-year research training program that will develop Dr. Patrick Hume into an independent basic and translational physician-scientist investigator. His long-term career goal is to advance the fields of COPD and macrophage biology through the elucidation targets to block or repair the development of small-airways disease in cigarette smokers. During this K08 Award, Dr. Hume will gain specific career development training and mentorship closely aligned with an innovative research plan. He proposes to study the role of Lyve-1 positive interstitial macrophages in the development of small airway pathology induced by chronic cigarette smoke. Given the broad applicability to COPD, this work is directly relevant to the NHLBI. Candidate: Patrick Human MD, PhD is a board-certified Pulmonary and Critical Care Medicine physician- scientist at National Jewish Health in Denver, CO. His record of basic science research, Ph.D. training and scientific publications demonstrates a firm commitment to a career as an academic clinician-scientist. Training: The proposed career development plan augments Dr. Hume’s prior mentored research during his undergraduate, doctoral, medical residency and fellowship training. He proposes to meet his short-term objectives through an integrated combination of intensive mentoring by internationally renowned experts in macrophage biology and COPD pathogenesis with didactic and hands-on experiences in (i) data analysis, (ii) cell biology, (iii) hyaluronic acid signaling, (iv) scientific writing and presentation, and (v) laboratory leadership. Mentor / Environment: Dr. Hume has close working relationships with highly experienced mentors and collaborators who contribute expertise in macrophage and lung biology (Drs. Janssen and Petrache), COPD pathogenesis and hyaluronic acid signaling (Dr. Petrache), matrix metalloproteinase biology and tissue remodeling (Dr. Redente), creation of transgenic mouse models (Dr. Matsuda) and design-based stereology (Dr. Smith). The proposed activities will be based at National Jewish Health, a top-ranked research institution. Research Project: The primary objective of this proposal is to identify the mechanism by which peribronchial interstitial macrophages (PBIMs) mediate airway wall remodeling and pathogenesis in response to chronic cigarette smoke exposure. Specifically, our studies will test the hypothesis that Lyve-1 expressed on a subset of PBIMs binds to hyaluronic acid resulting in matrix metalloproteinase 9 (MMP-9) production, leading to airway wall remodeling and fibrosis. This will be tested in human and murine lung tissue using quantitative morphometry and immunofluorescence, flow cytometry, in vitro models of hyaluronic acid signaling, and transgenic animal models. In doing so, the specific relationships between Lyve-1+ PBIM recruitment, MMP-9 production, and airway wall remodeling will be elucidated.


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 = $158,328 )
2026	2026	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	5	2/16/2026	NON-COMPETING CONTINUATION	$158,328
														Subtotal = $158,328

Issue Date FY: 2025 ( Subtotal = $158,328 )
2025	2025	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	12/23/2024	NON-COMPETING CONTINUATION	$158,328
														Subtotal = $158,328

Issue Date FY: 2024 ( Subtotal = $158,328 )
2024	2024	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	3	12/27/2023	NON-COMPETING CONTINUATION	$158,328
														Subtotal = $158,328

Issue Date FY: 2023 ( Subtotal = $158,328 )
2023	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	2	12/16/2022	NON-COMPETING CONTINUATION	$158,328
														Subtotal = $158,328

Issue Date FY: 2022 ( Subtotal = $158,328 )
2022	2022	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	1	12/13/2021	NEW	$158,328
														Subtotal = $158,328

Grand Total All Awards = $791,640

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Interstitial macrophages in cigarette smoke-induced small airway remodeling

Award Number: K08HL155894

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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