Thursday, July 3, 2025 7/3/2025

Regulation of mRNA homeostasis by PD-L1

Award Number: R16GM149263
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: 05/15/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2027

Group Awards By:

View Award Description

Regulation of mRNA homeostasis by PD-L1 - Abstract The goal of this project is to identify mechanisms by which immune checkpoint programmed death ligand 1 (PD-L1) regulates mRNA homeostasis of anti-apoptotic genes. As a cell surface protein, PD-L1 inhibits T cell responses, resulting in immune escape. However, PD-L1 also has important non-immune intracellular functions that are much less understood. Our recent studies show that IFNγ induces the nuclear translocation and accumulation of PD-L1 in ovarian and prostate cancer cells. In addition, our preliminary data indicate that suppression of the IFNγ-induced PD-L1 expression increases apoptosis and decreases mRNA levels of NFκB-dependent anti-apoptotic genes. Based on those ﬁndings, we will test the central hypothesis that the intracellular PD-L1 serves as a regulator of anti-apoptotic gene mRNA homeostasis. In Aim 1, we will determine whether PD-L1 increases the levels of anti-apoptotic genes by promoting their transcription, and/or whether it increases stability of their mRNAs in ovarian and prostate cancer cells. In Aim 2, we will determine whether PD-L1 directly binds to the anti-apoptotic gene promoters and facilitates their acetylation, and we will investigate whether PD-L1 binds the anti-apoptotic mRNAs and affects their subcellular localization. Although the project focuses on the NFκB-dependent anti-apoptotic genes, the results will likely reveal general mechanisms by which PD-L1 regulates synthesis and/or stability of other mRNAs. Immunotherapies targeting cell surface PD-L1 have shown impressive clinical outcomes in many cancers; however, only a fraction of patients achieves durable responses, highlighting our incomplete understanding of the mechanisms of PD-L1 functions. Findings from this study will provide the ﬁrst data on the mechanisms of how PD-L1 regulates mRNA homeostasis of anti- apoptotic genes. This information will advance our understanding of the intracellular, immune-independent functions of PD-L1, and may lead to the development of novel therapies that target PD-L1 anti-apoptotic functions in cancer cells.


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 = $164,000 )
2025	2025	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	3	6/5/2025	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2024 ( Subtotal = $164,000 )
2024	2024	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	001	2	6/18/2024	NON-COMPETING CONTINUATION	$16,400
2024	2024	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	2	3/11/2024	NON-COMPETING CONTINUATION	$147,600
														Subtotal = $164,000

Issue Date FY: 2023 ( Subtotal = $164,000 )
2023	2023	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	1	5/16/2023	NEW	$164,000
														Subtotal = $164,000

Grand Total All Awards = $492,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of mRNA homeostasis by PD-L1

Award Number: R16GM149263

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: 05/15/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer