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Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development

Award Number: K02DE029531
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/12/2023
PERIOD OF PERFORMANCE END DATE: 09/14/2025

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Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development - Dr. Suzuki's (PI) ultimate research goal is to identify environmental factors related to craniofacial pathophysiology and develop novel preventive and therapeutic strategies for environmental factor-associated oral diseases. This career development K02 award would provide the protected time 1) to gain expertise in physical analysis of skeletal tissues, including Micro-CT, FIB-SEM and QLF, and 2) to establish collaborative relationships with experts in environmental health science field. The proposed research project aims to characterize the health effects of fluorinated pollutants PFAS (per- and polyfluoroalkyl substances or organofluorine compounds) on tooth development. PFAS are a group of man-made organofluorine compounds, including Perfluorooctanoic acid (PFOA) and PFOA precursor, Fluorotelomer alcohols (FTOHs). PFAS do not readily breakdown in the environment and are water-soluble. PFAS can be found in drinking water and living organisms, including fish, animals and humans where PFAS can build up and persist over time. Laboratory animal studies showed that PFAS can cause tumors and adverse effects on reproductivity, development and immune system. Previous studies demonstrated that FTOHs (precursor of PFOA) induced tooth malformation, including degeneration of ameloblasts in rodent incisors. However, examination of how FTOHs alter tooth phenotype (physical and histological) is limited and the molecular mechanisms of how FTOHs affect tooth development are largely unknown. Our long-term goal is to identify the molecular mechanisms of PFAS adverse effects on odontogenesis. Our overall objective here is to establish PFAS (hazardous chemical) use in an animal model and determine how FTOHs affect amelogenesis in vivo. Our central hypothesis is that FTOHs induce DNA damage and mitochondrial damage to perturb ameloblast function during tooth development that results in enamel malformation. Our hypothesis has been formulated based on our preliminary data showing that PFOA inhibited cell proliferation, induced apoptosis, DNA damage and mitochondrial damage in ameloblast-like cell (LS8 cells). The impact of the proposed research is to define the effects of PFAS on tooth development and to highlight the molecular mechanisms involved in tooth malformation. Once PFAS adverse effects are identified in tooth formation, PFAS could be considered as a possible causative factor for cryptogenic abnormalities in dentinogenesis, including Molar Incisor Hypomineralisation (MIH) of which the etiology is unknown. We plan to test our central hypothesis and accomplish our overall objective by pursuing the Specific AIM: Identify FTOH effects on enamel phenotype in a mouse model.


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 = $148,614 )
2024	2024	NOVA SOUTHEASTERN UNIVERSITY, INC	3300 S UNIVERSITY DR	FT LAUDERDALE	FL	33328	BROWARD	USA	Oral Diseases and Disorders Research	002	4	7/30/2024	NON-COMPETING CONTINUATION	$148,614
2024	2022	NOVA SOUTHEASTERN UNIVERSITY, INC	3300 S UNIVERSITY DR	FT LAUDERDALE	FL	33328	BROWARD	USA	Oral Diseases and Disorders Research	001	2	2/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$4,026
2024	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	1	2/23/2024	NEW	-$4,026
														Subtotal = $148,614

Issue Date FY: 2023 ( Subtotal = $148,614 )
2023	2023	NOVA SOUTHEASTERN UNIVERSITY, INC	3300 S UNIVERSITY DR	FT LAUDERDALE	FL	33328	BROWARD	USA	Oral Diseases and Disorders Research	002	3	8/31/2023	NON-COMPETING CONTINUATION	$148,614
2023	2022	NOVA SOUTHEASTERN UNIVERSITY, INC.	3301 COLLEGE AVE	FORT LAUDERDALE	FL	33314	BROWARD	USA	Oral Diseases and Disorders Research	001	2	5/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$58,156
2023	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	1	5/16/2023	NEW	-$58,156
														Subtotal = $148,614

Issue Date FY: 2022 ( Subtotal = $131,252 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	1	9/5/2022	NEW	$131,252
														Subtotal = $131,252

Grand Total All Awards = $428,480

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Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development

Award Number: K02DE029531

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/12/2023

PERIOD OF PERFORMANCE END DATE: 09/14/2025

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