The Center of Children Oral Health Research (COHR) is a non-profit organization, emphasizing the translation of basic research to clinical care of oral diseases and dental developmental defects in children.
Our research focuses on the following topics:
Biomineralization
Tooth enamel is a highly mineralized hard tissue, uniquely comprised of millions of hexagonal carbonated hydroxyapatite (HAP) crystals. These crystals are very thin and extremely long, which determine the excellent mechanical properties of tooth enamel. Mineralized enamel crystals develop from a layer of enamel protein matrix that is predominated by amelogenins (>90%), which forms special nanostructures to modulate crystal formation.
The interactions between hydroxyapatite crystals, amelogenin/peptides and proteinase dynamically and delicately controlled the growth rate, direction and morphology of enamel crystals. By investigating the basic mechanisms by which this unique tooth forms, we can determine how genetic and environmental factors alter tooth formation.
Related articles
Bronckers AL, Lyaruu D, Jalali R, Medina JF, Zandieh-Doulabi B, DenBesten PK (2015). Ameloblast Modulation and Transport of Cl-, Na+, and K+ during Amelogenesis. J Dent Res. 94(12):1740-1747. PMICD: PMC4681480.
Dental caries research
Dental caries have multiple etiologies including diet, and genetic and epigenetic effects that alter (weaken) tooth structures.
We are identifying virulent gene(s) in caries-causing bacteria in children. To do this, we are using high-throughput genomic and meta-genomic assays. In addition, we are focusing on clinical studies, to identify new strategies for the prevention of dental caries.
Related articles
Abduweli Uyghurturk D, Lu Y, Urata J, Dvorak C. Den Besten P. Dental caries as a risk factor for bacterial bloodstream infection (BSI) in children undergoing hematopoietic cell transplantation (HCT). Peer J 2022 Sept. 23.
Environmental effects
Where we live, eat, work, and play profoundly influences our health. Tooth enamel formation is influenced by physical and emotional stressors. We have found evidence that early life adversity, which affects the HPA axis, can alter enamel formation. To better understand the link between stressors such as early life adversity and enamel formation, we are imaging the exfoliated (baby) teeth of children to identify differences in those with increased early life adversity. We are also using mouse models to better understand the biological mechanisms responsible for these stress-related changes.
Related articles
Boyce WT, Den Besten PK, Stamperdahl J, Zhan L, Jiang Y, Adler NE, Featherstone JD. Social inequalities in childhood dental caries: the convergent roles of stress, bacteria and disadvantage. Soc Sci Med. 2010 Nov; 71(9):1644-52.
Shaffer I, Nakano Y, Pham A, Short A, Nanci N, Zhang Y , Shemirani T, Den Besten PK. Effects of early life adversity on tooth enamel formation. Frontiers in Dental Medicine 2022. doi: 10.3389/fdmed.2022.894753.
Fluoride
Topically applied fluoride prevents dental decay from progressing, but in higher concentrations in drinking water can result in enamel fluorosis and other associated systemic effects. We are investigating the mechanisms for the cellular effects of fluoride, including fluoride-related changes in inflammation, cellular proteomics, and microbiome.
Related articles
Le MH, Nakano Y, Abduweli Uyghurturk D, Zhu L, Den Besten PK. Fluoride Alters Klk4 Expression in Maturation Ameloblasts through Androgen and Progesterone Receptor Signaling. Front Physiol. 2017; 8:925. PMID: 29249975. PMCID: PMC5715335.
Dionizio A, Abduweli Uyghurturk D, Melo CGS, Sabino-Arias T, Araujo TT, Ventural TMS, Perles VCM, Zanoni JN, Den Besten PK, Buzalaf, MAR. Intestinal changes associated to fluoride exposure in rats: Integrative morphological, proteomic and microbiomic analyses. Chemosphere 2021, June 273.
Abduweli Uyghurturk D, Goin DE, Martinez-Mier EA, Woodruff TJ, DenBesten PK. Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California. Environ Health. 2020 Apr 06; 19(1):38. PMID: 32248806. PMCID: PMC7132865
Den Besten P, Wells CR, Abduweli Uyghurturk D. Fluoride exposure and blood cell markers of inflammation in children and adolescents in the United States: NHANES, 2013-2016. 2022. Oct 27;21(1):102. doi: 10.1186/s12940-022-00911-6.
Genetic and epigenetic diseases
Genetic and epigenetic dental diseases in children, e.g. amelogenesis imperfecta and congenital loss of teeth. Of interest to us is the role of genetic defects in affecting tooth formation. We also are focused on strategies for clinical treatment, and changes in health policy to support the costs of such care for children with inherited tooth anomalies.
Related articles
Katsura K, Nakano, Y, Zang Y, Shemerani R, Li W, DenBesten P. WDR72 regulates vesicle trafficking in ameloblasts. Sci Rep. 2022 Feb 18;12(1):2820. doi: 10.1038/s41598-022-06751-1.2022