NYU Dentistry’s Rodrigo S. Lacruz Awarded $1.9M NIH Grant to Study Calcium Control in Dental Enamel
Rodrigo S. Lacruz, PhD, MS, an assistant professor of basic science and craniofacial biology at New York University (NYU) College of Dentistry, has been awarded a 5-year, $1.9 million grant from the National Institute of Dental and Craniofacial Research to study calcium control in dental enamel. The research has the potential to significantly impact scientific understanding of how calcium contributes to enamel formation.
Researchers hope to gain a better understanding of the impact of calcium in enamel mineralization and the physiological processes by which enamel crystals are formed with an overall objective to develop improved strategies for the prevention and treatment of caries.
Lacruz, in collaboration with Stefan Feske, MD, associate professor of pathology at NYU School of Medicine, and David I. Yule, PhD, professor of pharmacology and physiology at the University of Rochester Medical Center, have developed and will study several mouse models in which the genes Stim1 and Orai1 have been removed from specific tissues such as ameloblasts, sweat glands and salivary glands. By employing localized deletion — or conditional deletion — researchers will be able to analyze the specific function of Ca2+ influx via Ca2+ release-activated Ca2+ (CRAC) channels in these tissues without harming the body’s organs, according to an NYU news release.
The researchers developed the mouse models to better understand how CRAC channels modulate enamel development and mineralization. Study in this area has been limited because animals lacking Stim1 and Orai1 die soon after birth.
“Animal models enable us to look at the cells at different times and in different ways to assess the changes that occur when cells are deprived of calcium. In our case, we are interested in understanding what occurs when the enamel crystals themselves are also deprived of calcium,” Lacruz reports.
According to Lacruz, changes in the concentration of calcium (Ca2+) within the cell are modulated by Orai1 and Stim1 proteins in enamel-forming epithelial cells known as ameloblasts. Deficiencies in the normal functioning of these physiological mechanisms cause amelogenesis imperfecta. “These abnormalities can weaken the outer enamel surface, resulting in caries and other dental disease, including a massive breakdown of the enamel in patients with mutations in Stim1 and Orai1 genes,” he notes.
Lacruz’s team also plans to utilize animal models to understand the enamel problems experienced by Down syndrome (DS) patients, as they frequently present with a host of enamel deficiencies, including abnormal mineralization and thin enamel.
“It is our hope that the data we obtain will motivate physicians to involve dental practitioners early on in the treatment of patient with DS or patients with mutations to CRAC channels genes because we have established links between these diseases and deficiencies in enamel,” Lacruz explains.
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