Maternal alcohol exposure: impact on genetic control of craniofacial phenotype

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DESCRIPTION (provided by applicant): I am a postdoctoral fellow in the Division of Craniofacial Medicine, Department of Pediatrics, University of Washington in Seattle. My research interests lie in understanding the mechanisms (i.e. contributions of genes and environmental factors) responsible for human malformations, specifically craniofacial disorders, and normal phenotypic variation. With this in mind, my goal is to exploit tomographic imaging techniques as well as geometrics morphometrics as a means to quantitatively assess craniofacial phenotypes. I apply to this K99/R00 Pathways to Independence Award with the long-term goal becoming an independent researcher in the field of craniofacial dysmorphology. I have developed a research program to augment my background in quantitative morphology and 3D digital imaging with quantitative genetics and embryology to transition myself into an independent investigator in biomedical sciences. As the first step towards this goal, I will explore the effect of gestational alcohol exposure on the embryonic and post-natal craniofacial development of mice using: (1) state-of-the-art high-resolution in-vivo microCT and optical projection tomography, (2) traditional 3D shape quantification methods and a new 3D grid deformation methodology to characterize phenotypic differences, and (3) the use of a novel mouse model of moderate dose chronic ethanol exposure that produces FAS related measurable phenotypes in adults Long-term goals of this proposal are to (1) investigate the role of epigenetic programming in the presentation of alcohol-related malformations through detailed quantification of the craniofacial phenotype and (2) correlate genomic differences with these features to find epigenetically modified genes responsible for the phenotypic differences . In the future, these genes and the mechanism(s) by which they are modified in this model can be translated into clinical research and can offer the potential to find ways to better diagnose or even prevent or circumvent the negative effects of alcohol on fetal development. The role for epigenetic programming in alcohol-related phenotypes will be addressed through these specific aims: K1. To explore the effect of gestational alcohol exposure on embryonic craniofacial development: K2. To assess the impact of genetic variation on craniofacial development. R1. To characterize fetal craniofacial gene expression changes in response to gestational ethanol exposure R2. To explore the longitudinal effects of maternal alcohol consumption on post-natal craniofacial development R3. To develop a bioinformatics model infrastructure for making data and results from this proposal available. The University of Washington Schools of Medicine and Dentistry have over 1,800 full-time faculty members in 38 Departments, including 8 Nobel laureates. This year the UW Department of Pediatrics was ranked 6th by the US News and World Report among its peers.