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BRIDGING THE GAP: PROBING THE EFFECTS OF DNA METHYLATION ON BINDING DYNAMICS THROUGH NOVEL METHODOLOGY, AND HISTORICAL REVIEW
(Johns Hopkins University, 2015-12-11)
Though more than a decade has passed since the completion of The Human Genome Project, the knowledge derived from it has had little impact on our understanding of human health. The reason for this knowledge gap is that ...
CHARACTERIZATION OF GCN5 HISTONE ACETYLTRANSFERASE ACTIVITY AND BROMODOMAIN ACETYL-LYSINE BINDING FUNCTION
(Johns Hopkins University, 2015-02-12)
In eukaryotes, DNA is packaged into chromatin, which consists of the DNA wrapped around an octameric core of histone proteins (H2A, H2B, H3, and H4) which collectively comprise the nucleosome. Gene activation and silencing ...
Statistical methods for epigenetic data and structural magnetic resonance imaging
(Johns Hopkins University, 2016-04-04)
This dissertation introduces novel statistical methods for the analysis of high-dimensional biomedical data. First, we present a normalization method for DNA methylation microarray data, called Functional normalization ...
Epigenetic basis of stem cell identity in normal and malignant hematopoietic development
(Johns Hopkins University, 2015-07-31)
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by subpopulations of leukemia-initiating or leukemia stem cells (LSC) that give rise to clonally related non-stem leukemic blasts. The ...
ANALYSIS OF CONTEXT-DEPENDENT MODULATION OF EPIGENETIC GENE ACTIVITIES IN CAENORHABDITIS ELEGANS
We initiated a screen for trans-acting factors that modulate expression of a transgene reporter in C. elegans. In the process, we fortuitously generated transgene derivatives that exhibited an imprinting effect. Imprinting ...
Novel Histone Demethylase Inhibitors Synergistically Enhance the Effects of a DNA Hypomethylating Agent in Breast Cancer Cells
DNA methylation and histone methylation function together in the epigenetic regulation of gene expression, but these processes can be altered in cancer. Recently, the H3K4 demethylase, KDM5B, was shown to be amplified and ...
Genomics and Epigenomics of Common Human Metabolic and Heart Disease
(Johns Hopkins University, 2015-02-11)
The field of epigenetics is rapidly becoming recognized as playing an essential part in explaining common human disease. Here we probe DNA methylation in diabetes mellitus and associated metabolic phenotypes and coronary ...
Epigenetic changes during acute oxidative damage and non-small cell lung cancer epigenetic therapy
(Johns Hopkins University, 2014-02-10)
Cancers of virtually all types exhibit not only genetic abnormalities but also epigenetic ones which consist of DNA methylation and chromatin alterations. Among the key cancer specific changes involving interplay of these ...
Perinatal Epigenome Associated with Birth Outcomes and Exposure
(Johns Hopkins University, 2013-12-02)
Birth outcomes such as gestational age, or environmental exposures like mercury, serve either as one of the strongest predictors for neonatal, adolescent, and adult morbidity and mortality or associated with common diseases ...