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Hatch Wins Faculty Development Fellowship Award

Dr. Nan Hatch

Dr. Nan Hatch's 2012 Biomedical Research Award was named the B.F. Dewell Memorial Research Award, the designation given the most meritorious research award.

By Dr. Nan Hatch

I received my DMD from the Harvard School of Dental Medicine in 1999, an orthodontic certificate from the University of Washington in 2002 and a Ph.D. in molecular and cell biology from the University of Washington in 2005. After postdoctoral research training, I was appointed as an assistant professor in the University of Michigan's Department of Orthodontics and Pediatric Dentistry. I currently have 70 percent of my time committed to research.

As indicated by my 2012 AAOF BRA proposal, a primary focus of my research is in understanding molecular mechanisms of craniofacial development, with the goal of developing biologic therapeutics for the treatment of patients with craniofacial abnormalities. I am also engaged in studies to develop the use of biologic reagents for enhancement of orthodontic tooth movement, anchorage and retention. The remainder of my time is used for patient care, mentorship and teaching.

My AAOF-supported project investigates the pathogenesis of craniosynostosis. Craniosynostosis is a pediatric condition in which cranial bones prematurely fuse together. For more than a decade, scientists have known that craniosynostosis occurs in association with mutations in the genes for fibroblast growth factor receptors (FGFR's), yet the biologic process by which these mutations lead to craniosynostosis remains unknown. One mechanism by which mutations in FGF receptors may lead to abnormal cranial tissue mineralization and craniosynostosis involves tissue nonspecific alkaline phosphatase (TNAP), an enzyme whose activity is essential for the deposition and growth of hydroxyapatite crystals (the mineral component of bone).

Evidence in support of this mechanism is provided by studies from our laboratory and others showing that:

  1. FGFR activity inhibits TNAP enzyme expression.
  2. TNAP controls tissue mineralization.
  3. Craniosynostosis also occurs at high rates in children with inactivating mutations in the gene for TNAP.

Together these findings suggest a model in which activating mutations in FGF receptors inhibit TNAP enzyme expression, leading to diminished cranial bone mineralization with increased calcification of normally nonmineralized tissues, including the cranial sutures. Accordingly, here we propose to determine if enhanced TNAP expression will rescue the abnormal craniofacial phenotype of Crouzon FGFR2C342Y mice by crossing these mice with mice that over-express TNAP enzyme in osteoblastic cells.

If successful, results from these studies will lead to the development of pharmaceutics for the treatment of patients with craniosynostosis. Pertinent to the practice of orthodontics, results will also provide data to support future studies investigating the influence of FGF receptor activity on bone remodeling activities. As orthodontic tooth movement is dependent upon bone remodeling, this will provide important data for the future development of pharmaceutics to inhibit or enhance orthodontic tooth movement and/or relapse.

I am committed to becoming a successful academic orthodontist and independently funded biomedical researcher whose major emphasis will be in exploring questions of importance to our field. As competition for funding from NIH is extremely high, financial support from the AAOF has been and continues to be essential for generating the preliminary data required for success in obtaining R01 funding for this line of research and becoming an R01-funded investigator.