Monday, March 23, 2026 3/23/2026

PD-1 Mediated Regulation of Salivary Gland Integrity

Award Number: F31DE032593
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 01/15/2026
AWARD TERMINATION DATE: 03/04/2026

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PD-1 Mediated Regulation of Salivary Gland Integrity - Abstract Immune checkpoints play an important role in restraining the immune response, maintaining self- tolerance and preventing excessive collateral damage. Immune checkpoint blockade has revolutionized cancer immunotherapy but can lead to immune related adverse events (IrAEs). Patients receiving programmed cell death protein 1 (PD-1) blockade can develop IrAEs including vitiligo, colitis, endocrinopathies, and Sicca Syndrome, an autoimmune disease characterized by the accumulation of immune cells in the salivary and lacrimal glands, leading to deterioration and dysfunction. After immune cell activation, PD-1 is upregulated, and upon interacting with its ligand PD-L1, PD-1 signaling results in reduced proliferation, cytokine production, and cytotoxicity. PD-1 is expressed on infiltrating lymphocytes of the salivary gland including natural killer (NK) and T cells. Hyporesponsive immune cells in the salivary gland are thought to retain the integrity of this delicate tissue, while inadvertently contributing to viral latency. While trying to understand why lymphocytes in this organ are hyporesponsive, I unexpectedly found that genetic loss of PD-1 results in increased CD8+ T cell number and frequency in the salivary glands of naïve animals. Additional preliminary data suggests that NK cells may control CD8+ T cell expansion in the salivary gland. Based on these data, I hypothesize that in order to preserve the integrity of the salivary gland, NK cells may control T cell proliferation via the PD-1/PD-L1 axis in this organ. Therefore, in Specific Aim 1, I will elucidate the molecular mechanism by which PD-1 regulates CD8+ T cells in the salivary gland, and characterize the transcriptome and effector functions of the expanded CD8+ T cell population. In Specific Aim 2, I will characterize the potential immunopathological consequences of CD8+ T cell expansion in the PD-1 KO salivary gland by assessing histopathology and saliva secretions. These studies of PD-1 on salivary gland immune cells should provide insights for prevention and treatments of IrAEs. In preparation for the proposed work, my training has taken place in the outstanding immunology laboratory of Dr. Laurent Brossay, as well as within the supportive Pathobiology Graduate Program. My training experience will be enriched by attending and presenting at national and international conferences, and thoughtful mentoring by my sponsor. Completion of this proposal will prepare me with a repertoire of skills and the key foundational knowledge required for a successful career as an independent researcher.


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 = -$22,672 )
2026	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	001	3	3/3/2026	TERMINATION	-$17,968
2026	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	000	2	2/20/2026	NON-COMPETING CONTINUATION	-$4,704
														Subtotal = -$22,672

Issue Date FY: 2025 ( Subtotal = $53,338 )
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	001	3	7/28/2025	NON-COMPETING CONTINUATION	$53,338
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	002	3	8/8/2025	NON-COMPETING CONTINUATION	$0
2025	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	000	2	11/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $53,338

Issue Date FY: 2024 ( Subtotal = $52,274 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	001	2	9/18/2024	NON-COMPETING CONTINUATION	$0
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	000	2	7/22/2024	NON-COMPETING CONTINUATION	$52,274
														Subtotal = $52,274

Issue Date FY: 2023 ( Subtotal = $48,494 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	000	1	7/19/2023	NEW	$48,494
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Oral Diseases and Disorders Research	001	1	7/19/2023	NEW	$0
														Subtotal = $48,494

Grand Total All Awards = $131,434

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PD-1 Mediated Regulation of Salivary Gland Integrity

Award Number: F31DE032593

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 01/15/2026

AWARD TERMINATION DATE: 03/04/2026

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