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Determining the role of TP53 regulation in alveolar epithelial transitional cell state, and the contribution of alveolar epithelial transitional cell state to pulmonary fibrosis

Award Number: F31HL172360
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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ABSTRACT Respiratory disease is the third leading cause of death in the industrialized world. Pulmonary fibrosis (PF) is a progressively debilitating and terminal disease in which the normally pliable tissue of the lung is gradually replaced with rigid scar tissue. PF is an especially difficult respiratory disease, as there are no effective treatments and patients die within an average of three to five years of diagnosis. Current models suggest that alveolar injury and ineffective repair underlie the pathogenesis of PF and other lung diseases. However, the mechanisms by which injury in the alveolar epithelium contributes to fibrotic disease remain unclear. Single cell transcriptomics data demonstrate that a transitional state exists between the well characterized alveolar type 2 (AT2) and type 1 (AT1) epithelial cells. Furthermore, marker analysis of this transitional state in human PF lungs suggests that accumulation of transitional cells occurs in regions with dense myofibroblasts in fibrotic lungs. It is unclear what molecular mechanisms regulate the state of alveolar epithelial cells, but data from our lab has shown that TP53 is transiently upregulated in normal differentiation of AT2 to AT1 cells. This proposal details approaches to uncover the role of TP53 in regulating alveolar epithelial cell states, and to determine the impact of an alveolar epithelial transition state on pulmonary fibrosis. Understanding the mechanisms that drive these transitional states and their potential role in PF disease pathogenesis offers new avenues for developing novel therapies for fibrotic and other lung diseases.


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 = $47,694 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Lung Diseases Research	000	1	2/23/2024	NEW	$47,694
														Subtotal = $47,694

Grand Total All Awards = $47,694

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Determining the role of TP53 regulation in alveolar epithelial transitional cell state, and the contribution of alveolar epithelial transitional cell state to pulmonary fibrosis

Award Number: F31HL172360

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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