Dr. Hatch is an Associate Professor in the School of Dentistry and chair of the Department of Orthodontics and Pediatric Dentistry. His laboratory is focused on elucidating biochemical mechanisms and developing treatment strategies for skeletal craniofacial anomalies, with a focus on craniosynostosis (occurs in 1/2500 live births) and associated cranial base and long bone defects utilizing mouse models of disease. She also performs work to develop and test drug delivery systems for the control of orthodontic tooth movement.
Dr. Hatch earned her DMD in 1999 from the Harvard School of Dental medicine, then a certificate in orthodontics with a PhD in Molecular and Cell Biology in 2005 at the University of Washington. After completing her PhD she conducted postdoctoral research as a Tissue Engineering and Regeneration Training Grant trainee at the University of Michigan, followed by appointment as an Assistant Professor of Dentistry at the University of Michigan.
Dr. Hatch’s research interests include basic and translational research in skeletal development with a current focus on understanding the molecular etiology of craniosynostosis (occurs in 1/2500 live births) and associated skeletal anomalies, including work on the development of preventive treatment strategies to prevent and/or diminish severity of phenotype. We currently utilize a mutant FGFR2 mouse model of Crouzon syndrome and as well as conditional and global TNAP (tissue nonspecific alkaline phosphatase) mouse models of hypophosphatasia for quantitative analyses of cells and tissues. We also work with our biomaterial collaborators on designing and testing scaffolds containing cells and specific cell signaling inhibitors to develop a scaffold that could be inserted after surgical resection of prematurely fused cranial bones to prevent re-fusion of those bones.
We hypothesize that development of craniosynostosis and associated craniofacial skeletal anomalies (and long bones!) is a stem cell issue. Premature loss of progenitor cells and tissues could be caused by diminished renewal of progenitor cells, premature differentiation of progenitor cells and/or boundary mixing of progenitor with differentiated cells/tissues. Our most recent work suggests that diminished bone progenitor cell renewal may occur downstream of mitochondrial dysfunction caused by excessive FGF signaling and/or deficient expression of TNAP. This data would also be relevant to the muscle weakness and fatigue seen in hypophosphatasia patients (these patients have deficient TNAP). Therefore, we are looking for collaborators with expertise in mitochondria and/or muscle function.
Additionally, we have several lines of backcrossed mutant mice that show obvious differences in phenotype severity that is dependent upon genetic background strain. We are working on parent vs. F2 progeny quantitative phenotype comparisons in addition to generating RNA seq data. We would love to find collaborator(s) interested in understanding how genetic background strain modulates phenotype severity. This line of work is highly relevant to human disease as patients who have mutations in FGFR2 and TNAP have phenotypes that vary from mild to moderate to extremely severe. Identification of modulators of phenotype severity could identify targets to minimize phenotype development in patients that carry these mutations.
Finally, we also work with our biomaterial collaborators to design and test drug delivery systems utilizing proposed modulators of orthodontic tooth movement (bone agents, inflammatory agents) in rodent models of tooth movement (yes, we put braces on rats) to develop a system for localized and efficacious biologic control of orthodontic tooth movement and retention. If successful, such strategies could improve treatment efficiency and consistency of ideal treatment outcomes in the clinic.
Hatch NE(2010).FGF Signaling in Craniofacial Biologic Control and Pathology. Crit Rev Euk Gene Exp, Crit Rev Eukaryot Gene Expr,20(4): 295-311. PMID:21395503.
NamHK, LiJ, LiY, Kragor A and Hatch NE (2011). Ectonucleotide pyrophosphatase phosphodiesterase-1(Enpp1) regulates osteoblast differentiation via a catalysis independent mechanism.J BiolChem, 286(45):39059-71. PMCID:PMC3234731.
Hudson JB, Hatch NE, HayamiT, Shin JM, Stolina M, Kostenuik PJ, Kapila S (2012). Local Delivery of Recombinant Osteoprotegerin Enhances Post-orthodontic Tooth Stability. Calcif TissueInt 90(4):330-42. PMID:22382900.
Liu J, Nam HK, Wang E, Hatch NE(2013). Further Analysis of the Crouzon Mouse, Effects of the FGFR2C342Y Mutationare Cranial Bone Dependent. Calc Tissue Int 92(5):451-466. PMCID:3631296.
Liu J, Kwon TG, Nam HK and Hatch NE(2013). Craniosynostosis Associated FGFR2C342Y Mutant Bone Marrow Stromal Cells Exhibit Cell Autonomous Abnormalities in Osteoblast Differentiation and Bone Formation. Biomed Res Int. 2013;2013:292506. PMCID:3665166