Wednesday, August 20, 2025 8/20/2025

Cellular plasticity in salivary gland regeneration

Award Number: R01DE030626
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/02/2025
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Cellular plasticity in salivary gland regeneration - ABSTRACT Radiation therapy, the predominant treatment for head and neck cancers, causes irreversible damage to the salivary glands, due to the loss of secretory acinar cells. Recent data from our laboratory demonstrates that human and murine salivary glands initiate acinar cell regeneration after radiation treatment, but in contrast to injury by duct ligation, the salivary glands do not fully recover function. However, the regenerative potential exhibited in irradiated glands implies that therapeutic strategies may be developed to stimulate repair of radiation-induced damage. Emerging evidence suggests that cell plasticity, defined as the ability of differentiated cells to re-enter the cell cycle, is a means of supplying precursors for tissue regeneration. Evidence of cell plasticity has only recently been reported in salivary glands. In studies of glands injured by duct ligation or ionizing radiation, we have identified three specific cell populations that display plasticity. These include surviving regenerative cells that can repopulate duct-ligated glands, a heterogeneous population of cells co-expressing duct and acinar cell markers with unknown fate, and duct cells that can undergo lineage conversion to generate secretory acinar cells in irradiated glands. Cellular plasticity, and the ability to convert cells from another lineage in vivo, offer considerable potential for replacement of lost acinar cells. However, our knowledge of the mechanisms that induce, regulate, and constrain this process is limited. We propose to compare different injury models, for the response of salivary gland cells, and to define the conditions that induce plasticity. Lineage tracing, which heritably labels cells and their descendants, will be used to investigate how cells exhibiting plasticity contribute to regeneration, and the requirements for those cells to undergo lineage conversion. Single cell RNA sequencing will be used to characterize the cell types involved in regeneration, and gain insight into participating molecular pathways. The feasibility of stimulating regeneration of endogenous cells through the introduction of exogenous factors will be explored. These studies will determine how cellular plasticity and lineage conversion are involved in the response to injury and regeneration of the salivary glands. Identification of the cells involved and the conditions driving these processes may yield critical information for development of regenerative approaches to treat xerostomia.


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 = $454,108 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Oral Diseases and Disorders Research	001	5	5/14/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$454,108
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Oral Diseases and Disorders Research	003	5	6/11/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$206,771
2025	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	002	4	6/11/2025	NON-COMPETING CONTINUATION	-$206,771
2025	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	000	4	5/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $454,108

Issue Date FY: 2024 ( Subtotal = $445,025 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	000	4	3/6/2024	NON-COMPETING CONTINUATION	$408,698
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	001	4	6/10/2024	NON-COMPETING CONTINUATION	$36,327
														Subtotal = $445,025

Issue Date FY: 2023 ( Subtotal = $454,108 )
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	3	2/17/2023	NON-COMPETING CONTINUATION	$454,108
														Subtotal = $454,108

Issue Date FY: 2022 ( Subtotal = $466,315 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	2	6/7/2022	NON-COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	2	4/20/2022	NON-COMPETING CONTINUATION	$42,391
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	2	1/24/2022	NON-COMPETING CONTINUATION	$423,924
														Subtotal = $466,315

Issue Date FY: 2021 ( Subtotal = $451,425 )
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	1	2/19/2021	NEW	$451,425
														Subtotal = $451,425

Grand Total All Awards = $2,270,981

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Cellular plasticity in salivary gland regeneration

Award Number: R01DE030626

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/02/2025

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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