Project Details
Description
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.
Status | Active |
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Effective start/end date | 9/15/22 → 9/14/24 |
Funding
- National Institute of Dental and Craniofacial Research: $131,252.00
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