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The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.
Daria Gaykalova Lab
The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova... and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice. view more
Katherine Wilson Lab
Research in the Wilson Lab focuses on three components of nuclear lamina structure: lamins, LEM-domain proteins (emerin), and BAF.
These three proteins all bind each other directly, and are collectively required to organize and regulate chromatin, efficiently segregate chromosomes and rebuild nuclear structure after mitosis. Mutations in one or more of these proteins cause a variety of diseases including Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathy, lipodystrophy and diabetes, and accelerated aging.
We are examining emerin's role in mechanotransduction, how emerin and lamin A are regulated, and whether misregulation contributes to disease.
Sean Taverna Laboratory
The Taverna Laboratory studies histone marks, such as lysine methylation and acetylation, and how they contribute to an epigenetic/histone code that dictates chromatin-templated functions like transcriptional activation and gene silencing. Our lab uses biochemistry and cell biology in a variety of model organisms to explore connections between gene regulation and proteins that write and read histone marks, many of which have clear links to human diseases like leukemia and other cancers. We also investigate links between small RNAs and histone marks involved in gene silencing.