A University at Buffalo research team led by oral biologist Dr. Hyuk-Jae (Edward) Kwon has advanced the understanding of genetic disorders that weaken tooth enamel by turning off a gene known as KMT2D in mice.
The study, published in the Journal of Dental Research, marks the first in-depth investigation identifying KMT2D as a key regulator in enamel formation
Kwon, an associate professor in the Department of Oral Biology at UB’s School of Dental Medicine, and his team genetically engineered mice with the KMT2D gene deactivated in enamel-forming cells. The result: the mice developed teeth that were rough, chalky and thinner than normal—closely resembling the dental anomalies seen in patients with Kabuki syndrome, a rare genetic disorder.
“What we started to see is that these mice developed teeth that were very fragile and would break when they chewed on their chow,” said Kwon, DDS, PhD.
The KMT2D gene, also known as MLL4, encodes an enzyme called lysine-specific methyltransferase 2D, which plays a role in regulating gene expression in various tissues. The team discovered that enamel defects began even before the teeth emerged through the gums.
“We learned that KMT2D serves as a kind of ‘on switch’ for enamel-building in tooth cells,” Kwon said. “If this gene is missing or disrupted, the cells don’t receive the right signals, and the enamel-producing cells fail to develop properly.”
The research also suggests that targeting KMT2D with specific drugs could potentially reverse enamel defects and even prevent craniofacial birth defects.
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Exploring cleft palate and future therapies
The team is now testing candidate drugs in pregnant mice to determine whether they can prevent or reverse oral birth defects during mid-gestation. One focus is cleft palate, a common craniofacial anomaly also associated with Kabuki syndrome.
“When mice are born with a cleft palate, they die 100 per cent of the time,” Kwon said. “While humans can survive and undergo surgery, cleft palate can be a significant burden for patients and their families. If we could prevent these disorders from occurring, it would be a game changer.”
Recognition and funding
Kwon was recently awarded second place in the IADR Joseph Lister Award for New Investigators at the 2025 International Association for Dental, Oral and Craniofacial Research (IADR) Pan European Region General Session in Barcelona, Spain.
His colleague, Dr. Jung-Mi Lee, a research scientist in UB’s Department of Oral Biology, played a key role in the study by removing the gene in the oral epithelium. Lee has since received a two-year, $320,000 grant from the U.S. National Institute of Dental and Craniofacial Research to further investigate the gene’s regulatory mechanisms in dental regeneration.
“Our long-term goal is to understand how to regenerate organs,” Lee said. “And to do that, the most basic step is identifying the molecular mechanisms that drive tissue development.”
Other contributors to the study include Drs. Soo-Kyung Lee and Jae W. Lee, professors in UB’s Department of Biological Sciences and co-directors of the FOXGI Research Center, and Dr. Yungki Park, associate professor of biochemistry at the Jacobs School of Medicine and Biomedical Sciences.
