Thursday, November 21, 2024 11/21/2024

Epigenetic and Non-epigenetic Role of SIRT1 in Fluoride-induced Cell Stress Administrative Supplement.

Award Number: R01DE027648
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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This is an application to the Administrative Supplements for Continuity of Biomedical and Behavioral Research Among First-Time Recipients of NIH Research Project Grant Awards (NOT-OD-23-032), granted for the PI's (Dr. Maiko Suzuki) parent R01 grant (R01DE027648) entitled “Epigenetic and non-epigenetic role of SIRT1 in fluoride-induced cell stress”. The PI's overarching research objective in the dental-oral-craniofacial field is to identify environmental factors related to craniofacial pathophysiology and to develop novel preventive and therapeutic strategies for environmental factor-associated oral diseases, including tooth malformation, periodontitis and oral cancer. To attain the objective, in this supplement, the PI will develop the current R01 project into fluorinated compounds (per- and poly- fluoroalkyl Substances; PFAS), which are newly highlighted as environmental pollutants. PFAS are a large group of artificial fluorinated organic compounds that have generated increased public attention due to their toxicity and adverse health effects. The molecular mechanisms of PFAS effects on dental-oral-craniofacial pathophysiology are largely unidentified. In the parent R01 award, we focus on the molecular mechanisms of fluoride on enamel development. Our preliminary results demonstrated that, as well as fluoride, fluorinated organic compounds PFAS could cause adverse effects on enamel formation in vitro and in vivo. Recent studies have demonstrated the association between PFAS exposure and some types of cancer. However, the PFAS effects on Head and Neck Cancer (HNC) are largely unidentified. In this supplement, we propose to develop the parent research project into PFAS-mediated HNC pathology. The objective is to determine the biological effects of PFAS on HNC in vitro. Our preliminary data suggest that PFAS could promote HNC invasiveness and metastasis. We preliminary discovered that perfluorooctanoic acid (PFOA; a most studied PFAS) increased the expressions of epithelial-mesenchymal transition (EMT) markers and promoted cell migration (wound healing assay) in a murine squamous cell carcinoma cell line (SCC7) in vitro. SCC7 has been used as an oral cancer and head and neck cancer model in vitro and in vivo. Our previous study demonstrated that fluoride and PFOA increased ROS generation to cause oxidative stress in ameloblast-like cells. Based on our previous studies and preliminary data, we hypothesize that ROS may play a critical role in PFOA-mediated cancer EMT and cell migration. This hypothesis will be tested by the Aim: To determine the role of ROS in PFOA-mediated EMT and cell migration in murine and human oral squamous cell cancer (OSCC) cell lines in vitro. Upon successfully completing this proposed study, the results will provide new insights that PFAS could be considered a possible metastatic factor in HNC. Findings from this supplement and parental projects will improve our understanding of the health effects of fluorinated environmental factors (fluoride and PFAS) on enamel malformation and head and neck cancer pathophysiology.


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: 2024 ( Subtotal = $68,700 )
2024	2024	NOVA SOUTHEASTERN UNIVERSITY, INC	3300 S UNIVERSITY DR	FT LAUDERDALE	FL	33328	BROWARD	USA	Oral Diseases and Disorders Research	004	6	5/30/2024	SUPPLEMENT FOR EXPANSION	$68,700
2024	2023	NOVA SOUTHEASTERN UNIVERSITY, INC	3300 S UNIVERSITY DR	FT LAUDERDALE	FL	33328	BROWARD	USA	Oral Diseases and Disorders Research	003	6	2/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$874,673
2024	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	002	5	2/23/2024	NON-COMPETING CONTINUATION	-$360,850
2024	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	001	4	2/23/2024	NON-COMPETING CONTINUATION	-$364,700
2024	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	3	2/23/2024	NON-COMPETING CONTINUATION	-$149,123
														Subtotal = $68,700

Issue Date FY: 2023 ( Subtotal = $57,493 )
2023	2023	NOVA SOUTHEASTERN UNIVERSITY, INC.	3301 COLLEGE AVE	FORT LAUDERDALE	FL	33314	BROWARD	USA	Oral Diseases and Disorders Research	004	6	6/16/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$364,493
2023	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	003	5	6/15/2023	NON-COMPETING CONTINUATION	$0
2023	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Oral Diseases and Disorders Research	001	1	3/13/2023	NEW	-$307,000
2023	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Oral Diseases and Disorders Research	002	1	4/19/2023	NEW	$0
2023	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Oral Diseases and Disorders Research	000	1	1/20/2023	NEW	$0
														Subtotal = $57,493

Issue Date FY: 2022 ( Subtotal = $360,850 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	5	5/20/2022	NON-COMPETING CONTINUATION	$360,850
														Subtotal = $360,850

Issue Date FY: 2021 ( Subtotal = $364,700 )
2021	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	4	5/20/2021	NON-COMPETING CONTINUATION	$364,700
														Subtotal = $364,700

Issue Date FY: 2020 ( Subtotal = $370,753 )
2020	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	3	5/15/2020	NON-COMPETING CONTINUATION	$370,753
														Subtotal = $370,753

Issue Date FY: 2019 ( Subtotal = $307,001 )
2019	2019	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	2	4/22/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$307,001
														Subtotal = $307,001

Issue Date FY: 2018 ( Subtotal = $379,060 )
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Oral Diseases and Disorders Research	000	1	5/30/2018	NEW	$379,060
														Subtotal = $379,060

Grand Total All Awards = $1,908,557

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Epigenetic and Non-epigenetic Role of SIRT1 in Fluoride-induced Cell Stress Administrative Supplement.

Award Number: R01DE027648

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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