Research

Functional Tests Of Non-Coding DNA Variants Associated With Risk For Orofacial Clefting

• Genome-wide association studies (GWAS) and linkage studies have identified many DNA variants that are associated with elevated risk for isolated oral facial clefting, a common birth defect. However, it is currently unclear which of these variants are actually pathogenic, and by what mechanism they are pathogenic. We address both these questions with fine-mapping of GWAS data and analysis of whole genome sequence data to prioritize SNPs, medium-throughput tests of such variants in reporter assays in a cell line, zebrafish and mice, and molecular analyses of SNPs that the previous assays reveal to be functional.

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Dissecting The Transcriptional Network Governing Differentiation Of Periderm

• Orofacial is a common disease with a major impact on the affected individual, their family and society. Here, we will determine the gene regulatory network for periderm, an embryonic tissue that is critical for development of the palate. Our new knowledge will identify candidate genes and help identify pathogenic variants located in regulatory elements which will improve risk assessment and provide new targets for rational therapies.

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Regulation Of The Melanocyte Lineage By The AP2 Transcription Factor Family

• Stem cells are subject to differentiation, leading to loss of tissue homeostasis, or unregulated growth, potentially leading to cancer. The balance of pluripotency, proliferation, and differentiation in melanocyte stem cells, a model of other adult stem cells, is regulated by a poorly-understood regulatory pathway including transcription factors MITF and TFAP2A. Our proposed experiments will illuminate this pathway in the context of normal development, and in a syndrome caused my mutations in TFAP2A.

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