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$1 million grant

Feng receives NIH grant to explore possible cause of bone and tooth defects

Dr. Jian “Jerry” FengDr. Jian “Jerry” Feng, professor in biomedical sciences, recently was awarded a $1.16 million grant from the National Institutes of Health’s National Institute of Dental and Craniofacial Research to study a potential cause of abnormalities during bone and tooth formation.

His NIH R01 grant project, titled “DMP1 mutations: defects in odontogenesis,” will receive $1,162,500 for total direct costs over a five-year period.

Feng and co-principal investigator Dr. Chunlin Qin, assistant professor in biomedical sciences, will study the formation of dentin, the largest component of teeth, to ultimately shed light on the prevention of structural defects. Proper tooth development requires the precise coordination of space in the jaw and the correct timing during cell growth and mineralization. In searching for the genes required for normal tooth formation, Feng and colleagues have studied dentin matrix protein 1 (DMP1), a protein found abundantly in bone and dental pulp. DMP1 also is found in cells called odontoblasts, which are located on the surface of dental pulp and secrete dentin. Feng and his colleagues have shown that DMP1 is crucial for the proper mineralization of bone and dentin.

In his previous studies of mice that were bred without DMP1, Feng found that this missing protein caused abnormalities in their teeth. They had enlarged pulp chambers, increased width of the predentin area, lack of mineralization and delayed third molar formation.

Coincidentally, Feng and coworkers found that humans with a condition called autosomal recessive hypophosphatemic rickets (ARHR) had bone and dentin defects very similar to those he observed in the mice without DMP1. Upon further investigation, the researchers discovered two DMP1 mutations in these patients.

Feng proposes to repair the tooth and bone defects in ARHR patients by retargeting the expression of DMP1. To test this hypothesis, Feng will study the genetics and physiology of DMP1 mutations by creating a mouse model with the same DMP1 mutations found in the ARHR patients.

The long-term goals of this new project are threefold. First, it will generate an animal model mimicking human mutations in ARHR patients. Second, the project will explore how DMP1 controls the development of teeth. Finally, the research will identify which bioactive fragment(s) of DMP1 in mice are similar to those found in humans. It is hoped that the mouse model and the study findings will benefit the public, specifically patients with ARHA.

The project period began September 30 and will continue until June 30, 2013. Dr. Rena D'Souza, professor and chair of biomedical sciences, serves as a consultant.

D'Souza says, “Dr. Feng is one of the leaders in the area of skeletal biology. He is an outstanding faculty researcher and educator, and we at HSC-BCD are fortunate to have him working with us. The findings from this recently funded grant will undoubtedly make an important impact on the current knowledge about the molecular mechanisms that drive tooth and bone formation.”

Feng expresses his gratitude to Qin and D'Souza for their support of this research program.

Feng joined HSC-BCD in 2006 after spending eight years on the faculty, ultimately as professor, in the oral biology department at the University of Missouri-Kansas City. Previous to his appointment at UMKC, he was a research assistant professor in the medical and dental schools at the University of Texas Health Science Center at San Antonio. He holds an M.D. and a master’s degree in physiology from the University of Qindao Medical College in China and a Ph.D. in physiology from the University of Connecticut.