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Determining Sox10-mediated plasticity in irradiated salivary gland cells

Award Number: F30DE032585
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: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 03/01/2027

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Determining Sox10-mediated plasticity in irradiated salivary gland cells - PROJECT SUMMARY/ABSTRACT Therapeutic irradiation, a commonly used treatment for head and neck cancer patients, irreversibly damages the salivary glands (SGs). Current therapies aim to alleviate the resulting xerostomia (dry mouth syndrome) but fail to address the underlying mechanism of dysfunction, thus new strategies for tissue regeneration are needed. Given that endogenous repair of irradiated SGs is majorly hampered due to the loss of saliva-producing acinar cells and their progenitors, inducing the ability of the remaining ductal cells to behave as acinar progenitors (i.e. plasticity) is an attractive repair strategy. Inducing plasticity is a complex process whereby transcription factors often interact with chromatin modulators, such as Hdac1, to induce downstream gene regulators of progenitor cell potency. Interestingly, it has been shown that some irradiated ductal cells can spontaneously revert towards a progenitor-like state to enable acinar differentiation under severe stress conditions, although too few undergo this transition to fully restore the gland. In order to enhance plasticity, we recently demonstrated that overexpression of transcription factor Sox10 in non-irradiated ductal cells induces plasticity, allowing acinar differentiation ex vivo. However, whether this set-up is applicable to irradiated ductal cells is unclear. Based on preliminary data, we hypothesize that plasticity can be induced in irradiated ductal cells through overexpression of Sox10, which activates a downstream regulatory network through binding with Hdac1. To prove this hypothesis, our objectives are to evaluate the binding capacity of Sox10 to Hdac1, as well as the altered downstream gene network and acinar formation capacity in irradiated cells after inducing a Sox10-mediated plasticity. Overall, these data will then be used to formulate a new translational therapy in our in vivo radiation- induced xerostomia animal model to aid in the repair of SGs post-radiation.


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 = $55,338 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	3	8/12/2025	NON-COMPETING CONTINUATION	$564
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	3	3/4/2025	NON-COMPETING CONTINUATION	$54,774
														Subtotal = $55,338

Issue Date FY: 2024 ( Subtotal = $54,774 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	2	6/18/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	2	2/22/2024	NON-COMPETING CONTINUATION	$53,494
														Subtotal = $54,774

Issue Date FY: 2022 ( Subtotal = $52,552 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	1	9/5/2022	NEW	$52,552
														Subtotal = $52,552

Grand Total All Awards = $162,664

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Determining Sox10-mediated plasticity in irradiated salivary gland cells

Award Number: F30DE032585

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: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 03/01/2027

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