Wednesday, July 2, 2025 7/2/2025

Molecular Regulation of Progressive Pulmonary Fibrosis

Award Number: R35HL150829
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Molecular Regulation of Progressive Pulmonary Fibrosis - ABSTRACT Our laboratory has been focused on elucidating the molecular mechanisms that regulate progressive pulmonary fibrosis for over two decades. My contributions to the field of idiopathic pulmonary fibrosis research include using matrix hyaluronan as a model molecule to dissect the molecular mechanisms of progressive lung fibrosis. We have identified the role of hyaluronan fragments in regulating lung inflammation. We discovered that hyaluronan and hyaluronan receptors have roles in lung inflammation and in lung stem cell regeneration. We discovered an invasive fibroblast phenotype in mice as well as in idiopathic pulmonary fibrosis explants. We are generally credited with expanding the notion that matrix is more than just glue and has a dynamic role in regulating lung biology. One aspect of our work that I have been proud of is that we have published much of our science in non-subspecialty journals of reasonable impact. This suggests that although we study the lung, the concepts we have put forward have been deemed of interest to a broader audience. The goals of this R35 application are to identify the epithelial-mesenchymal interactions that lead to unremitting fibrosis. Specifically, we propose in this R35 to identify mechanisms for AEC2 failed regenerative capacity in mouse and man, to identify mechanisms for mesenchymal expansion in mice with impaired AEC2 renewal capacity, to identify the mechanisms by which beta-arrestin1 and CD44 regulate the invasive fibroblast phenotype, and to identify mechanisms by which the invasive fibroblast impairs AEC2 cell renewal. Augmenting scientific knowledge in understanding the underlying mechanisms and the mode of actions of these interactions in lung fibrosis could significantly aid therapeutic development for patients with progressive pulmonary fibrosis. My belief is that we need a drug that promotes alveolar progenitor cells renewal and a drug that targets pathogenic fibroblasts such as invasive fibroblasts. The studies that we propose in this R35 application may suggest new leads for therapeutic intervention we are not yet aware of and we want to have the freedom to pursue them. Furthermore, the benefit of longer-term funding of this award allows me to train the next generation of scientists as I have done during my time at Duke University as well as currently here at Cedars.


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: 2025 ( Subtotal = $762,785 )
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	6	3/6/2025	NON-COMPETING CONTINUATION	$762,785
														Subtotal = $762,785

Issue Date FY: 2024 ( Subtotal = $830,589 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	5	2/29/2024	NON-COMPETING CONTINUATION	$762,785
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Lung Diseases Research	001	5	6/21/2024	NON-COMPETING CONTINUATION	$67,804
														Subtotal = $830,589

Issue Date FY: 2023 ( Subtotal = $847,538 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	4	2/27/2023	NON-COMPETING CONTINUATION	$847,538
														Subtotal = $847,538

Issue Date FY: 2022 ( Subtotal = $847,538 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Lung Diseases Research	001	3	2/24/2022	NON-COMPETING CONTINUATION	$762,781
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Lung Diseases Research	002	3	6/15/2022	NON-COMPETING CONTINUATION	$84,757
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	2	1/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $847,538

Issue Date FY: 2021 ( Subtotal = $847,538 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	2	2/15/2021	NON-COMPETING CONTINUATION	$847,538
														Subtotal = $847,538

Issue Date FY: 2020 ( Subtotal = $847,538 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Lung Diseases Research	000	1	2/14/2020	NEW	$847,538
														Subtotal = $847,538

Grand Total All Awards = $4,983,526

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Molecular Regulation of Progressive Pulmonary Fibrosis

Award Number: R35HL150829

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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