Rodrigo Lacruz, PhD, MSc, professor of molecular pathobiology at NYU Dentistry, has received a grant from the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institutes of Health’s INCLUDE project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) to study salivary gland and tooth enamel formation on a molecular level in those with Down syndrome. The five-year grant (1R01DE032846-01) provides $1.5 million in funding for the initial three-year period, with additional funding in the ensuing two years.
This research will build on Lacruz’s existing work on the oral health of people with genetic disorders including Down syndrome, also supported by funding from NIDCR. Lacruz received a five-year, $2.3 million grant (2R01DE027679-05) earlier this year to support his work on the role of mitochondria in the formation of tooth enamel in those with genetic disorders.
People with Down syndrome face several issues with their oral health, including poor saliva production and defects in their tooth enamel, which can present as thinner enamel and hypomineralization. The molecular mechanisms responsible for these differences are not known.
Saliva is essential to overall oral health, preventing bacterial growth that can lead to cavities and helping with speech and taste. Saliva and tooth enamel together provide a barrier against bacteria, and deficiencies in them can have a significant impact on health and quality of life.
The goal of this research is to understand how salivary gland and enamel formation are altered in Down syndrome on a molecular level and to define the role of a gene called RCAN1 and a protein called calcineurin in this process. The researchers will use mouse models of Down syndrome to study whether RCAN1 disrupts enamel crystal formation in Down syndrome by altering mitochondrial function in ameloblasts, and whether suppressing calcineurin signaling disrupts calcium signaling in salivary glands, leading to poor saliva production.
“This research will advance our understanding of the mechanisms through which changes in normal mitochondrial function, such those associated with Down syndrome, impact oral health and will elucidate the mechanisms contributing to poor saliva production in this population,” said Lacruz.