1:45 Epigenetic Programming of Cell Differentiation
Shilpa Kadam, Ph.D., Research Investigator, Epigenetics, Novartis Institutes for BioMedical Research, Inc.
Within the eukaryotic nucleus, packaging of DNA into chromatin is an essential regulatory feature of many critical processes such as replication, repair, recombination and transcription. The ability of a cell to program our genome through modifications in chromatin structure determines which genes are expressed at a given time and under appropriate environmental signals. This process is extremely essential for normal cellular function, tissue differentiation and development. The significance of this process is underscored by the fact that specific errors in the transcriptional pattern of cells are correlated with chronic and acute human diseases such as cancer, Alzheimer’s and Parkinson’s disease. To insure the integrity of genomic expression, cells have evolved sophisticated mechanisms to regulate DNA accessibility through chromatin. This remarkable plasticity is governed by diverse family of multi-protein complexes that enzymatically regulate chromatin structure and activity. Using stem cells as a model system we have been interested in understanding how cells are epigenetically programmed during proliferation and tissue specific differentiation. Towards this goal we carried out genome wide analysis to identify key epigenetic factors that would play a role in tissue specific differentiation. In this regard implication of histone deacetyl complexes in stem cell regulation will be presented.
2:15 Chromatin Landmarks in Embryonic Stem Cells
Matthew G. Guenther, Ph.D., Whitehead Institute for Biomedical Research
Cell-type specific patterns of gene expression within an organism are maintained, at least in part, through epigenetic inheritance of chromatin states. These chromatin states are established and propagated through specific chemical modifications of nucleosomal histones that are often associated with a distinct transcriptional outcome (Gene activation or inactivation). We have undertaken a genome-wide analysis of histone modifications associated with gene activation in human embryonic stem (ES) cells and find a much greater role for their usage than previously appreciated. We discuss a surprising role for histone H3 lysine-4 trimethylation (H3K4me3) and other chromatin landmarks in the context of global regulation of gene transcription.
2:45 Prognostic DNA Methylation Biomarkers in Ovarian Cancer
Kenneth P. Nephew, Ph.D., Associate Professor, Assistant Director, Basic Science Research, Indiana University School of Medicine
Aberrant DNA methylation, now recognized as a contributing factor to
neoplasia, often shows definitive gene/sequence preferences unique to specific cancer types. Correspondingly, distinct combinations of methylated loci can function as biomarkers for numerous clinical correlates of ovarian and other cancers. We used a microarray approach to identify methylated loci prognostic for reduced progression-free survival
(PFS) in advanced ovarian cancer patients. We successfully identified 220 candidate
PFS-discriminatory methylated loci. Of those, 112 were found capable of predicting PFS with 95% accuracy. Such ovarian cancer biomarkers represent a promising approach for the assessment and management of this devastating disease.
3:15 Spotlight Presentation (Sponsorship Available)
3:45 Blood Based Screening for Colorectal Cancer and Preneoplastic
Disease
Drs. Matthias Ebert, Gastroenterologist, Medizinische Klinik des Klinikum Rechts der Isar, Germany and Cathy Lofton-Day, Ph.D., Vice President Molecular Biology, Diagnostics, Epigenomics,
Inc.
The use of DNA methylation alterations as biomarkers in oncology is a rapidly growing field. Utilization of these biomarkers in blood requires highly sensitive and highly specific assays that detect their methylated targets in an overwhelming background of unmethylated DNA. We have identified a number of biomarkers for colorectal cancer through a systematic approach beginning with discovery and verification of markers on target cancer and preneoplastic tissues to optimize sensitivity and on control tissues to optimize specificity, followed by validation of surviving candidates on plasma samples from similar sample types. These studies have resulted in a number of biomarker assays that can discriminate colorectal cancer plasma samples from healthy controls and biomarker panels with potential to identify early neoplastic changes.
4:00 Refreshment Break, Poster and Exhibit Viewing
4:45 Panel Dicussion
with Speakers
5:15-7:00 Networking Reception in Exhibit Area
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