By Mary L. Marazita, PhDAn important new research initiative was announced in October 2009 by the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health. This initiative is establishing a nationwide consortium that will develop an innovative research resource called “FaceBase.” Although the initiative is new, there have been several years of groundwork by NIDCR and researchers around the country to bring the concept to fruition.The overall aim of FaceBase is to provide the craniofacial and dental research community with a resource to achieve a comprehensive understanding of craniofacial and dental development, thereby enhancing our ability to investigate, diagnose, and ameliorate human craniofacial and dental diseases and disorders. Many researchers are applying the tools of genomics, proteomics, and phenomics in human and animal models to unravel craniofacial and dental development at the most basic level. To date there have been no existing projects that attempt to merge the necessary genetic, developmental biology, and informatics expertise that would eventually lead to a comprehensive systems biology understanding of the mechanisms that underlie complex craniofacial and dental phenotypes. The vision for FaceBase is to build the necessary framework (e.g., service-oriented architecture) of databases and informatics tools necessary to allow a synthesis of existing and to-be-generated data throughout the craniofacial and oral complex. This major endeavor will be accomplished in stages. At the first stage of the FaceBase project, the focus will be on the midface and aspects related to orofacial clefts (primarily cleft lip and cleft palate), but the framework put in place by the FaceBase Consortium will readily allow expansion to all parts of the craniofacial and oral complex.NIDCR has now awarded 11 grants to accomplish the first stage of the FaceBase project. The FaceBase consortium is structured with a centralized database and management Hub, and 10 individual research projects, with all aspects overseen by NIDCR program staff led by Dr. Stephen Scholnick. Dr. Mary Marazita of the University of Pittsburgh School of Dental Medicine and Dr. Jeffrey Murray of the University of Iowa School of Medicine are the co-principal investigators of the FaceBase Management and Coordination Hub which will develop the FaceBase web portal (www.FaceBase.org, under construction but soon to be rolled out), develop the FaceBase bioinformatics architecture, maintain complex data repositories and develop data mining tools for the repositories, establish a bio-repository of relevant tissues from humans and/or animal models, and develop comprehensive educational activities. Ongoing developments in bioinformatics — that is, the application of information technology to the field of molecular biology — have set the stage for a project of the magnitude of FaceBase. Therefore, Dr. Michael Becich, chair of the University of Pittsburgh Department of Biomedical Informatics, is a key co-investigator in the FaceBase effort. FaceBase will take advantage of existing open access software tools, many developed by Dr. Becich or his collaborators, which will be modified for use in FaceBase.The other 10 FaceBase grants are a mixture of technology projects, which will develop laboratory or informatics tools for FaceBase, and research projects, which will create data that will be available through FaceBase. The projects include (1) “Oral Clefts: Moving from Genome-wide Studies Toward Functional Genomics”; Principal Investigator (PI): Terri Beaty, Johns Hopkins University; (2) “Research on Functional Genomics, Image Analysis, and Rescue of Cleft Palate”; PI Yang Chai, University of Southern California; (3) “Identification of miRNAs Involved in Midfacial Development and Clefting”; PIs David Clouthier and Kristen Artinger, University of Colorado, and Johon Postlethwait, University of Oregon; (4) “Genetic Tools and Resources for Orofacial Clefting”; PIs Leah Rae Donahue and Stephen Murray, the Jackson Laboratories; (5) “Functional Analysis of Neural Crest and Palate: Imaging Craniofacial Development”; Scott Fraser, California Institute of Technology; (6) “3-D Analyses of Normal Facial Variation: Data Repository and Genetics”; PIs Mary Marazita and Seth Weinberg, University of Pittsburgh; (7) “Global Gene Expression Atlas of Craniofacial Development”, PI Steven Potter, Children’s Hospital Medical Center of Cincinnati; (8) “Shape-Based Retrieval of 3-D Craniofacial Data”; PI Linda Shapiro, University of Washington; (9) “Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate”, PI Richard Spritz; University of Colorado; (10) “Genome-Wide Atlas of Craniofacial Transcriptional Enhancers”, PI Axel Visel, University of California — Lawrence Berkeley Lab.In addition to the new tools and data generated by the 10 new FaceBase projects, the Hub will also include access to existing data resources that have never before been available to the craniofacial and dental research community in a coordinated format. This wealth of information will be available free and publicly accessible to the research community. The FaceBase research initiative will provide comprehensive research tools that will facilitate understanding the genetic basis of craniofacial development and the mechanisms underlying craniofacial diseases and disorders with the long-term goal of accelerating development of molecular medicine for improved risk assessment, effective prevention, screening and treatment strategies, as well as functional restoration in oral, dental, and craniofacial disorders. Taken together, these collaborative projects will provide a comprehensive knowledge base for a systems level understanding of normal and abnormal craniofacial development. This is critical for tackling the challenge of treatment and prevention of complex disorders affecting craniofacial and dental tissues.Access to comprehensive web-based tools for creating communities of individuals focused around a common interest has never been greater nor the resources more powerful. The craniofacial community has somewhat self-assembled into disparate groups working collaboratively in human and animal models and in disciplines ranging from epidemiology and genetics to embryology and imaging. These groups have contributed to substantial advances in our understanding of craniofacial and dental disorders over the last three decades. FaceBase will allow these efforts will move forward more rapidly by, for example, making unpublished and prepublication data universally available, facilitating communication between international groups, and by making common resources available to enhance research efforts. Improved educational opportunities fostered by FaceBase will nurture both the lay population in better understanding the nature of craniofacial and dental disorders, and will also encourage students and faculty to develop interests in this rich area of research. The long-term outcome of FaceBase will be a platform that will greatly accelerate the pace of understanding of the causes of craniofacial and dental disorders, and will provide many opportunities for translational components that can be targeted at improvements in clinical care.
Mary L. Marazita, PhD, was born and raised in Michigan. She attended Michigan State University as an undergrad (graduated 1976), and holds a PhD in genetics (with a concentration in biostatistics) from the University of North Carolina, Chapel Hill. Her postdoctoral work was at the University of Southern California and the University of California, Los Angeles, and she is a board-certified PhD Medical Geneticist. Her PhD work was under the mentorship of Dr. Robert Elston, one of the founders of the field of human statistical genetics. Since receiving her PhD in 1980 she has been continuously working in the field of human genetics, utilizing approaches from all aspects of genetic epidemiology (segregation analyses, linkage analyses, association analyses, GxE approaches, case-control, and family-based approaches). Dr. Marazita currently is on the faculty of the University of Pittsburgh, serving as the associate dean for research in the School of Dental Medicine, director of the Center for Craniofacial and Dental Genetics, professor and vice chair of the Department of Oral Biology (School of Dental Medicine). She has secondary appointments in the Department of Human Genetics, the Clinical and Translational Science Institute and the Department of Psychiatry. Dr. Marazita has served on several NIH working groups and steering committees over the years. For example, she currently is a member of two steering committees for the National Human Genome Research Institute (NHGRI): the GENEVA (Gene Environment Association) Studies Steering Committee (guiding several GWAS studies under the NIH Genes and Environment Initiative), and the PhenX Steering Committee (developing standardized phenotypic measures for GWAS studies of complex traits). She has been a keynote speaker at multiple national and international forums including the NIDCR 60th Anniversary Symposium at the 2008 AADR/IADR meeting, keynote speaker for 2008 Annual Meeting of the Colombian Association of Human Genetics, invited speaker for the 2008 ECLAMC Annual Meeting (Latin American Birth Defects Registry, Rio de Janeiro, Brazil), and the keynote speaker for the 2007 International Foundation of Cleft Lip and Palate (Beijing, China). Currently, Dr. Marazita’s research focuses on the human genetics of complex traits, specifically, birth defects (primarily cleft lip, cleft palate, and other craniofacial anomalies), oral health, preterm birth, and other complex phenotypes. She has more than 200 peer-reviewed publications, and substantial grant support, primarily from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health. Dr. Marazita conducts statistical genetic analysis to investigate the familial patterns of complex disorders, with a view to identifying the etiologic genes in both U.S. and international populations. A major current focus is statistical analyses and genetic mapping studies of nonsyndromic cleft lip with or without cleft palate in China, India, Guatemala, Spain, Hungary, and various sites in the U.S. An important aspect of these studies is expanding the phenotype of orofacial clefting to include features such as orbiculoris oris muscle anatomy, VPI, and asymmetry. A second major focus is investigating factors contributing to oral health disparities, for example genetic, microbiological, and epidemiological factors contributing to caries and other oral health phenotypes in Appalachia. Her third major focus has been on the genetics of preterm birth through collaborations with Drs. Jeff Murray and John Dagle (University of Iowa), Dr. Hyagriv Simhan (University of Pittsburgh, Magee-Women's Hospital of UPMC), and Drs. Dawn Misra and Betsy Foxman (University of Michigan). Dr, Marazita’s role in the preterm birth projects is to provide the statistical genetic/genetic epidemiological approaches for analyzing the resulting genetic and environmental data.