Thursday, October 23, 2025 10/23/2025

Understanding mechanisms and consequences of T cell co-receptor regulated RNA maturation

Award Number: R01AI155499
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/05/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

Group Awards By:

View Award Description

Understanding mechanisms and consequences of T cell co-receptor regulated RNA maturation - Project Abstract/Summary. T cells are unique in their requirement for two activation signals to become functional. This separation of powers between the T cell receptor (TCR) and co-receptors, such as CD28, allows exquisite regulation of T cell responses. In recent years, T cell co-receptors have emerged as valuable targets of immunotherapy for autoimmune diseases and cancer. In autoimmunity blocking activating co-receptors can reduce the destructive effects of T cells on normal tissue, while in cancer blocking inhibitory co-receptors can activate a T cell response against malignant cells. However, co-receptor targeted immunotherapy often fails to produce desired results. Moreover, there remain large gaps in knowledge of how co-receptors coordinate the myriad cellular changes that allow T-cells to gain functional properties. The project proposed in this grant application will explore a novel mechanism by which T cell co-receptors coordinate changes in RNA maturation important for T-cells to generate sufficient numbers and make key molecules that allow them to kill other cells. These killer properties underlie the ability of T cells to contain infectious diseases and control tumor growth or to damage healthy tissue in autoimmune diseases. Preliminary studies provide evidence that CD28 signaling coordinates many changes in alternative splicing of newly made RNAs through effects on the RNA binding protein ARS2. Alternative splicing allows one gene to code for several different proteins by changing how the RNA produced from that gene is assembled. We find that in activated T cells CD28-ARS2 dependent alternative splicing of the mRNA coding for metabolic enzyme pyruvate kinase favors production of an isoform, known as PKM2, with known proliferation promoting properties. Proposed studies seek to 1) determine if alternative splicing to PKM2 induces changes in how T cells use nutrients to fuel proliferation, 2) examine how ARS2 regulates alternative splicing in T cells, and 3) establish CD28 regulated changes in alternative splicing as potential modulators of immunotherapy. The long-term goals of these studies are to understand how RNA binding proteins and RNA maturation shapes gene expression during the process of T-cell activation and to determine if such mechanisms of gene regulation can be therapeutically targeted to alter T-cell function in patients with cancer or autoimmune 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: 2025 ( Subtotal = $501,412 )
2025	2025	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Allergy and Infectious Diseases Research	000	5	3/14/2025	NON-COMPETING CONTINUATION	$501,412
														Subtotal = $501,412

Issue Date FY: 2024 ( Subtotal = $516,920 )
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Allergy and Infectious Diseases Research	001	4	5/23/2024	NON-COMPETING CONTINUATION	$51,691
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Allergy and Infectious Diseases Research	000	4	3/5/2024	NON-COMPETING CONTINUATION	$465,229
														Subtotal = $516,920

Issue Date FY: 2023 ( Subtotal = $516,920 )
2023	2023	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Allergy and Infectious Diseases Research	000	3	3/27/2023	NON-COMPETING CONTINUATION	$516,920
														Subtotal = $516,920

Issue Date FY: 2022 ( Subtotal = $516,920 )
2022	2022	HEALTH RESEARCH, INC.	ELM AND CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Allergy and Infectious Diseases Research	000	2	3/9/2022	NON-COMPETING CONTINUATION	$516,920
														Subtotal = $516,920

Issue Date FY: 2021 ( Subtotal = $533,970 )
2021	2021	HEALTH RESEARCH, INC.	ELM AND CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Allergy and Infectious Diseases Research	000	1	4/5/2021	NEW	$533,970
														Subtotal = $533,970

Grand Total All Awards = $2,586,142

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Understanding mechanisms and consequences of T cell co-receptor regulated RNA maturation

Award Number: R01AI155499

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/05/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer