Wednesday, April 24, 2024 4/24/2024

Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis

Award Number: U01HL153000
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Abstract We have developed a 3D bioengineered human induced pluripotent stem cell (iPSC) derived model of IPF that displays progressive fibrosis and closely phenocopies several characteristics associated with IPF. This model is an extension of our 2D model of progressive fibrosis (Vijayaraj et al., Cell Reports – in press). To make our progressive fibrosis model specific to IPF, we have developed it into a model system that utilizes the lung 3D architecture and specific cell types. Our 3D model displays additional features of IPF such as airway epithelial cell (AEC) apoptosis, epithelial-mesenchymal transition (EMT) and replacement of alveolar architecture. Our proposal aims to improve and validate this 3D model such that it will be amenable to a high throughput drug discovery platform in a patient specific manner for precision medicine. Our project aims to use our unique stem/progenitor cell models of IPF to increase our understanding of the disease and for drug discovery. Specific Aim 1. To improve and validate the 3D bioengineered human iPSC derived model of IPF A. To validate the 3D model of IPF by performing extensive characterization of the model compared to human IPF lung tissue. B. To characterize the heterogeneity of IPF seen across different patients. C. To characterize the 3D IPF model by known genetic risk factors. Specific Aim 2 – To use our 3D bioengineered iPSC-derived model to study cellular plasticity in IPF To profile cellular plasticity of AECs in our 3D model of IPF and compare it to human IPF tissue using single cell RNA sequencing. Specific Aim 3 – To develop and standardize a high throughput drug screening (HTS) platform to identify new anti-fibrotic therapies using the 3D model of IPF A. To develop a HTS using the 3D model of IPF. B. To develop robust, image analysis pipelines that employ a combination of advanced deep learning techniques and traditional image processing methods to generate quantitative measures of tissue health. C. To develop and run a pilot HTS to identify small molecules that will perform one or more of the following a) prevent apoptosis of AEC; b) enhance apoptosis of mesenchymal cells; c) decrease expression of ¿-SMA. Our team includes international experts who study lung biology (Gomperts, UCLA), biology of fibrosis (Vijayaraj, UCLA), an IPF clinician and researcher (Belperio, UCLA), lung pathologist (Wallace, USC), iPSC airway epithelial cell differentiation (Spence, Michigan), single cell RNA seq and analysis (Plath, UCLA), and high throughput drug discovery (Damoiseaux, UCLA) with machine learning algorithms for analysis (Shattuck, UCLA). We are a highly collaborative team that is working together using innovative, patient relevant research approaches to tackle the challenges of modeling IPF to identify new therapies.


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: 2024 ( Subtotal = $567,380 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Lung Diseases Research	000	4	1/17/2024	NON-COMPETING CONTINUATION	$567,380
														Subtotal = $567,380

Issue Date FY: 2023 ( Subtotal = $630,424 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Lung Diseases Research	000	3	1/11/2023	NON-COMPETING CONTINUATION	$630,424
														Subtotal = $630,424

Issue Date FY: 2022 ( Subtotal = $630,424 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Lung Diseases Research	002	2	6/14/2022	NON-COMPETING CONTINUATION	$63,043
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Lung Diseases Research	001	2	12/20/2021	NON-COMPETING CONTINUATION	$567,381
2022	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Lung Diseases Research	000	1	12/3/2021	NEW	$0
														Subtotal = $630,424

Issue Date FY: 2021 ( Subtotal = $488,421 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Lung Diseases Research	000	1	2/12/2021	NEW	$488,421
														Subtotal = $488,421

Grand Total All Awards = $2,316,649

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis

Award Number: U01HL153000

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer