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Tooth enamel is the hardest substance in the human body, protecting the innermost layers of the tooth, including the dentin and pulp.

Some genetic disorders, however, result in weakened enamel that can lead to tooth sensitivity, decay and broken teeth. They include amelogenesis imperfecta, where the enamel is too thin or poorly formed, and Kabuki syndrome, characterized by distinct facial features, intellectual disabilities and dental anomalies — including weakened enamel.

To better understand how the gene KMT2D affects the development of tooth enamel, UB oral biologist Hyuk-Jae “Edward” Kwon and his team genetically engineered mice with the KMT2D gene turned off in the cells that form enamel. What they found was that the mice’s teeth were very similar to human patients with Kabuki syndrome: rough, chalky and thinner than normal.

Their research, which also suggested that targeting KMT2D with certain drugs could reverse weakened enamel and even prevent craniofacial birth defects, was published in the Journal of Dental Research. It marks the first in-depth study showing KMT2D as a key player in building enamel.

It has also catapulted Kwon, associate professor in the Department of Oral Biology, School of Dental Medicine, onto a worldwide stage.

On June 24, he was awarded second place in the IADR Joseph Lister Award for New Investigators competition, held during the 2025 International Association for Dental, Oral and Craniofacial Research (IADR) with the Pan European Region (PER) General Session and Exhibition in Barcelona, Spain.

Jung-Mi Lee, research scientist in the Department of Oral Biology who worked with Kwon on the project, eliminated the gene in the epithelium — or the surface tissue of the oral cavity.

“What we started to see is that these mice developed teeth that were very fragile and would break when they chewed on their chow,” Kwon says.

The team also discovered the enamel defects started even before the teeth emerge through the gums.

“We learned the KMT2D serves as a type of on switch for enamel-building in tooth cells,” he says. “If this gene is missing or disrupted, the cells don’t get the right signals and the enamel-making cells do not develop properly.”

Other researchers who contributed to the research and the paper included Soo-Kyung Lee and Jae W. Lee, professors in the Department of Biological Sciences, College of Arts and Sciences, who also co-direct UB’s FOXGI Research Center, and Yungki Park, associate professor of biochemistry in the Institute for Myelin and Glia Exploration at the Jacobs School of Medicine and Biomedical Sciences.

The team is now planning to test candidate drugs in pregnant mice to see if they could reverse or prevent birth defects in the oral cavity during the mid-gestation period.

Cleft palate, another major orofacial anomaly seen in Kabuki syndrome, is also being investigated through a related project in the lab.

“When mice have a cleft palate at birth, they die 100% of the time,” Kwon explains. “While humans survive, and there is surgery to correct it, cleft palate can be a huge burden on patients and their families. If we could find a way to correct or prevent these diseases and disorders from occurring, it would be a game changer.”

He emphasizes the importance of studying epigenetics, which involves environmental factors that can alter cell behavior without changing DNA sequences, as a rapidly advancing area in developmental biology.

“In the future, if we were to replace dental implants, we would want a precise blueprint — an instruction manual, so to speak — for how to build a tooth,” he says. “That kind of knowledge would be essential for successfully regenerating organs.”

Kwon and his team have a strong starting point.

In addition to the awards and recognition for Kwon, the research laid the foundation for a two-year, $320,000 grant from the National Institute of Dental and Craniofacial Research that was just awarded to Jung-Mi Lee. The grant will support Lee’s independent investigation into the gene’s regulatory mechanisms in dental regeneration and help establish her own research program while also building on ongoing collaborative work with Kwon.

“Our long-term goal is to understand how to regenerate organs,” Kwon says. “And to do that, the most basic step is identifying the molecular mechanisms that drive tissue development.”