Tuesday, August 19, 2025 8/19/2025

Targeting Lipogenic and Angiogenic Mediators in Pulmonary Fibrosis

Award Number: SC1GM121287
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2011
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Targeting Lipogenic and Angiogenic Mediators in Pulmonary Fibrosis - Abstract: Due to the major challenges in both diagnostic and therapeutic modalities in pulmonary fibrosis (PF), it is important to continue identifying novel and viable drug targets to combat pathogenesis associated with the disease. We propose to use a combination of traditional molecular biology techniques and high-throughput lipidomics and proteomics approaches to identify novel protein and lipid biomarkers, and investigate their contribution to PF. The long-term goal is to develop an effective therapeutic strategy against PF, and this study is directly relevant to the mission of National Heart, Lung and Blood Institute. The overall objective of the proposed study is to identify novel biomarkers and study the interplay between lipogenic and angiogenic mediators that may be targeted for treatment of PF. Recent evidence suggests an important role for lipid mediators in PF, but little is known about the deregulation of overall lipid composition in disease progression. Preliminary data suggests a critical role for fatty acid synthase (FASN), an important lipogenic enzyme associated with lung injury, in bleomycin (BLM)-induced PF. Aim 1 is designed to investigate the role of FASN in the pathogenesis of PF and identify key FASN-associated lipid and protein partners. Preliminary proteomic analysis of BLM-treated mouse lung tissue identified Phosphatidylinositol-3-kinase/Protein Kinase B (PI3K/Akt) and Wnt (Wingless Integration-1)/beta(β)-catenin signaling pathways as the two most important fibrotic pathways involved. PI3K/Akt and Wnt/β-catenin pathways have been shown to potentiate fibrotic response, and we have reported on the critical role of vascular endothelial growth factor (VEGF), a direct target of PI3K/Akt pathway, in regulating fibrosis. FASN is known to regulate VEGF in other lung diseases such as asthma, and activate Wnt/β-catenin signaling in breast and prostate cancers. We hypothesize that FASN exerts its effects in PF by regulating PI3K/Akt>VEGF and Wnt/β-catenin pathways. Aim 2 is designed to investigate the mechanistic effect of Wnt/β-catenin and PI3K/Akt>VEGF signaling on regulation of FASN in BLM-induced PF. Our ongoing in vivo studies demonstrates that FASN inhibitor Orlistat significantly inhibited BLM-induced PF. Furthermore, a strong interplay has emerged between FASN, VEGF and Wnt/β-catenin signaling in PF. Aim 3 is designed to evaluate whether anti-FASN agents such as Orlistat mediate lung fibrosis by regulating PI3K/Akt>VEGF and Wnt/β-catenin signaling pathways, and investigate the potential development of a co-therapy regimen involving Orlistat and inhibitors of the PI3K/Akt>VEGF and Wnt/β-catenin pathways. Investigation of this crosstalk and identification of related key biomarkers will be important for the increased understanding of the molecular mechanisms involved in the pathogenesis of PF and will facilitate development of potential therapeutic and preventive strategies for this fatal disease.


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 = -$437 )
2025	2021	HAMPTON UNIVERSITY	200 WILLIAM R HARVEY WAY	HAMPTON	VA	23669	HAMPTON CITY	USA	Biomedical Research and Research Training	000	9	11/26/2024	NON-COMPETING CONTINUATION	-$437
														Subtotal = -$437

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	HAMPTON UNIVERSITY	200 WILLIAM R HARVEY WAY	HAMPTON	VA	23668	HAMPTON CITY	USA	Biomedical Research and Research Training	000	9	6/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $295,000 )
2021	2021	HAMPTON UNIVERSITY	200 WILLIAM R HARVEY WAY	HAMPTON	VA	23668	HAMPTON CITY	USA	Biomedical Research and Research Training	000	9	5/20/2021	NON-COMPETING CONTINUATION	$295,000
														Subtotal = $295,000

Issue Date FY: 2020 ( Subtotal = $295,000 )
2020	2020	HAMPTON UNIVERSITY	200 WILLIAM R HARVEY WAY	HAMPTON	VA	23668	HAMPTON CITY	USA	Biomedical Research and Research Training	000	8	6/5/2020	NON-COMPETING CONTINUATION	$295,000
														Subtotal = $295,000

Issue Date FY: 2019 ( Subtotal = $336,500 )
2019	2019	HAMPTON UNIVERSITY	100 E QUEEN ST	HAMPTON	VA	23668	HAMPTON CITY	USA	Biomedical Research and Research Training	000	7	5/3/2019	NON-COMPETING CONTINUATION	$336,500
														Subtotal = $336,500

Issue Date FY: 2018 ( Subtotal = $343,000 )
2018	2018	HAMPTON UNIVERSITY	100 E QUEEN ST	HAMPTON	VA	23668	HAMPTON CITY	USA	Biomedical Research and Research Training	000	6	6/26/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$343,000
														Subtotal = $343,000

Grand Total All Awards = $1,269,063

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Targeting Lipogenic and Angiogenic Mediators in Pulmonary Fibrosis

Award Number: SC1GM121287

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2011

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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