Thursday, November 21, 2024 11/21/2024

Elucidating the Mechanisms of Salivary Gland Dysfunction Following Gamma-Irradiation Utilizing an Experimental and Computational Approach

Award Number: F31DE030670
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Individuals diagnosed with head and neck cancer undergo radiation therapy as a standard treatment. However, in the process of using radiation therapy to shrink the tumor, the salivary glands are inadvertently and irreversibly damaged. This damage manifests as a loss of saliva secretion, occurs rapidly without marked cell death, and leads to deleterious effects, including loss of taste, oral infections, and xerostomia (dry mouth). The mechanism by which this early loss of function occurs, is currently unknown and presently there is little in the form of treatment, with most options being palliative. Thus, there is a pressing need to expand our understanding of salivary gland physiology and the effects of γ-irradiation on both the structure and function of the salivary gland. This proposal utilizes experimental techniques including confocal, Stimulated Emission Depletion (STED) and intravital microscopy. Each technique will be employed for use in a variety of assays to investigate the structural and functional consequences of acute γ-irradiation on salivary glands. This in vitro and in vivo experimental approach will additionally be used in combination with computational modeling through a long-term collaboration to understand in detail the effect of γ-irradiation on secretion. In an iterative manner, experimental data will be input to the computation model and subsequently used to make further predictions which will be experimentally tested- furthering our understanding of physiology and pathology of salivary glands. In these studies, this experimental-computational approach will be used to determine how alterations within the salivary gland impact its function, leading to dry mouth, and an eventual permanent loss of glandular tissue and function. This proposal addresses three different mechanisms that may dictate this loss of function. These include an alteration in functioning of gap and tight junctions, calcium signaling, and mitochondrial bioenergetics. By examining each of these aspects, the experimental data can be integrated into the computational model. The great utility of this approach is that many iterations of computational experiments can be completed in parallel with these in vitro and in vivo studies and used to suggest further experiments and make predictions. The dynamic utilization of this computational-experimental approach will facilitate understanding how an alteration in a component of the gland’s secretory machinery following γ-irradiation might alter saliva production. Ultimately, this approach is designed to forecast potential novel therapeutic approaches for treating γ-irradiation induced salivary dysfunction.


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 = -$18,826 )
2025	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	000	3	10/23/2024	NON-COMPETING CONTINUATION	-$18,826
														Subtotal = -$18,826

Issue Date FY: 2024 ( Subtotal = -$11,054 )
2024	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Oral Diseases and Disorders Research	000	3	5/21/2024	NON-COMPETING CONTINUATION	-$11,054
														Subtotal = -$11,054

Issue Date FY: 2023 ( Subtotal = $48,494 )
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	3	2/28/2023	NON-COMPETING CONTINUATION	$942
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	3	1/17/2023	NON-COMPETING CONTINUATION	$47,552
														Subtotal = $48,494

Issue Date FY: 2022 ( Subtotal = $47,552 )
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	$717
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	2	5/25/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	2	12/27/2021	NON-COMPETING CONTINUATION	$46,836
														Subtotal = $47,552

Issue Date FY: 2021 ( Subtotal = $46,836 )
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	1	1/21/2021	NEW	$46,320
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	1	2/1/2021	NEW	$516
														Subtotal = $46,836

Grand Total All Awards = $113,002

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Elucidating the Mechanisms of Salivary Gland Dysfunction Following Gamma-Irradiation Utilizing an Experimental and Computational Approach

Award Number: F31DE030670

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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