Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the role of granzyme A in CD8 T cell exhaustion

Award Number: F30AI197373
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/20/2026
PERIOD OF PERFORMANCE END DATE: 04/19/2030

Group Awards By:

View Award Description

Investigating the role of granzyme A in CD8 T cell exhaustion - PROJECT SUMMARY CD8 T cells directly mediate the specific killing of virally infected and cancerous cells. Upon recognizing a specific antigen presented on a target cell, T cells become activated and acquire effector function, including the secretion of perforins and granzymes to cause target cell death. However, when the antigen is not readily cleared, as in chronic viral infections and cancer, T cells enter a state of exhaustion where they express co- inhibitory molecules like PD-1 and lose effector capacity. T cell exhaustion is a major contributor to the persistence of chronic viral infections and cancer. Inhibition of CD8 T cell co-inhibitory pathways is the basis of immune checkpoint blockade (ICB), which reinvigorates T cell anti-tumor responses and can dramatically improve cancer outcomes. However, patient responses are variable, which can partially be attributed to the heterogeneity of exhausted T cell populations. ICB acts directly on a subset of exhausted T cells called progenitor cells, which expand and differentiate into intermediate cells, which have increased effector function. However, intermediate cells are short-lived and become terminally exhausted cells with low effector function. Understanding the mechanisms of differentiation from progenitor to terminal exhausted states will vastly improve patient responses to immunotherapy. Our group recently found that mouse and human exhausted T cells express high levels of granzyme A (GzmA). Granzymes are a class of serine proteases that mediate target cell death, with granzymes A and B being the most abundant granzymes. While granzyme B (GzmB) is essential for T cell cytotoxicity and is reduced during exhaustion, little is known about the role of GzmA. Our preliminary findings suggest a conversion from GzmB in effector T cells to GzmA in exhausted T cells, but it remains unknown how this process impacts the differentiation and function of exhausted T cells. We hypothesize that GzmA expression is a compensatory mechanism in response to GzmB downregulation that functions to increase cytotoxic capacity during T cell exhaustion. We will mechanistically dissect the role of GzmA in CD8 T cell exhaustion by generating a murine Gzma-/- model and tracking T cell function during chronic viral infection and tumor progression. Aim 1 will use flow cytometry, single-cell RNA-sequencing, and functional assays to determine the CD8 T cell-intrinsic effects of GzmA deletion during the longitudinal progression of T cell exhaustion during chronic viral infection. Aim 2 will test how GzmA deletion impacts anti-tumor T cell function in the tumor microenvironment. Together, these aims will define the function of GzmA in exhausted T cells and elucidate novel mechanisms in CD8 T cell exhaustion. The collaborative training environment, the cutting-edge core facilities, and the many experts in T cell immunology at Baylor College of Medicine and the Texas Medical Center will strongly support the success of this project. The integrative training plan will comprehensively prepare the applicant for an academic physician- scientist career studying mechanisms of T cell biology to improve clinical outcomes for rheumatology patients.


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: 2026 ( Subtotal = $50,526 )
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	001	1	4/17/2026	NEW	$0
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	1	4/17/2026	NEW	$50,526
														Subtotal = $50,526

Grand Total All Awards = $50,526

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the role of granzyme A in CD8 T cell exhaustion

Award Number: F30AI197373

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/20/2026

PERIOD OF PERFORMANCE END DATE: 04/19/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer