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TUESDAY, MARCH 16, 2010
7:00 am Conference Registration
7:30 Breakfast Presentation (Sponsorship Opportunity) or Morning Coffee
8:30 Chairperson’s Remarks
Kenneth P. Nephew, Ph.D., Professor of Medical Sciences; Cellular and Integrative Physiology; Obstetrics and Gynecology; Co-Director, Center for Integrated Cancer Biology; Assistant Director, Basic Science Research, Indiana University Simon Cancer Center
8:35 Application of Epigenetics in Discovery of Cancer Biomarkers and Clinics
Zdenko Herceg, Ph.D., Head, Epigenetics, International Agency for Research on Cancer
Tumor DNA and plasma DNA from individuals with tumors harbors epigenetic changes and these changes are tumor specific with the potential to serve as highly specific biomarkers. Importantly, DNA methylation changes appear early in tumor development and can be found in virtually every type of human cancer, thus they can provide particularly attractive markers with broad application in diagnostics and risk assessment. The development of epigenetic biomarkers for cancer-bearing individuals could similarly enhance the management of their disease. Conceptual advances and remarkable technological advances in Epigenetics and Epigenomics that allow powerful screening of large series of samples with unprecedented resolution and application of novel approaches to reveal highly specific epigenetic biomarkers will be discussed.
9:05 Epigenetic Regulation of Inflammation in Diabetes and Nutritional Strategies
Sridevi Devaraj, Ph.D., Professor, Pathology & Laboratory Medicine, University of California Davis Medical Center
This presentation will discuss work on epigenetic regulation of inflammation in diabetes, which is a major cause of diabetic complications, such as heart disease. Also, we will discuss how these can be reversed with anti-inflammatory and nutritional strategies.
9:35 Whole-Genome Bisulfite Sequencing Reveals Widespread DNA Methylation Differences Between Tumor and Matched Normal Tissues
Benjamin P. Berman, Ph.D., Senior Research Associate, USC Epigenome Center, Keck School of Medicine, University of Southern California
We have used a powerful new technology, whole-genome bisulfite sequencing (BS-seq or MethylC-seq), to determine the complete single base-pair resolution DNA methylome of a colon tumor and matched normal mucosa from the same patient. The two tissues show strikingly divergent methylation patterns, revealing a high-resolution epigenomic landscape that both illuminates a large amount of prior work regarding cancer-specific DNA methylation, but also opens up whole new areas of investigation. We will characterize the relationship between methylation changes and gene expression in well-studied genomic contexts such as CpG islands and known genes, then move on to discuss how this global dataset expands our understanding of epigenetics in poorly studied contexts such as long-range enhancers and large, multi-gene chromatin domains.
10:05 Life Does Not Have to be Complicated: Simplify DNA Methylation Analysis 
Larry Jia, MD., Director of Research & Development, Zymo Research Corporation
As importance of DNA methylation in gene regulation and epigenetic control becomes more evidence, there is increased demand for simpler and reliable platforms for DNA methylation analysis tools. An innovative method is developed to increase the throughput of loci specific DNA methylation analysis and dramatically simplified the complicated work flow of DNA methylation detection by using existing common laboratory instruments. In addition, simplified genome wide DNA methylation analysis platform is developed to display genome wide DNA methylation pattern uniformly. These new platforms will be useful in DNA methylation research in complement existing tools.
10:20 Networking Coffee Break, Exhibit & Poster Viewing
11:00 DNA Methylation in Cell Differentiation and Reprogramming
Guoping Fan, Ph.D., Associate Professor, Human Genetics, University of California, Los Angeles
We profile DNA methylation in gene promoters in human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and differentiated cells. Whereas genes with decreased methylation in iPSCs are primarily developmental genes, genes exhibiting increased methylation in iPSCs encode proteins for specialized differentiation pathways. Supervised clustering analysis identified unique methylation sites in iPSCs, which effectively serve as a biomarker for iPSCs. Our data indicates that selective demethylation and de novo methylation are equally important for stem cell differentiation and reprogramming.
11:30 Developing of Dual RTK/HDAC Inhibitor with Improved Efficacy for Anti-Cancer Activity
Xian-Ping Lu, Ph.D., Chief Executive Officer & Chief Scientific Officer, Chipscreen Biosciences
Epigenetic modulation by HDACi has a clear advantage in terms of immunosurvillance via activating NK- or T cell-mediated cytotoxicity against tumor cell survival or metastasis. HDACi may also to be a potential inhibitor in modulation of cancer stem cells transition. However, such a favorable biological property associated with HDACi may not be enough to be a treatment regiment by itself unless other anti-cancer property such as inhibition of VEGF or other RTK can be incorporated into treatment. We have developed such single molecule inhibitor that is highly potent against both VEGF/HDAC1, 2 selectively with in vivo efficacy and right biological property listed above.
12:00 pm Close of Morning Session
Sponsored by
12:15 Luncheon Presentation
Complete Next Generation Sequencing Data Analysis Made Easy: Live Demonstration of Transcriptome and ChIP-Seq Analysis From Raw Data to Biology
Martin Seifert, Ph.D., VP of Support Services and Business Development for Genomatix Software, GmbH
Besides genotyping, Genomatix provides very fast workflows for the analysis of transcriptome and ChIP-Seq experiments. These workflows include high efficiency mapping and clustering of raw sequence tags, data integration into up to date genome annotation, and downstream analysis of tag enriched regions. We will demonstrate (live) the possibilities for extending genome annotation, splice variant detection, and the discovery of new transcriptional units. In addition, we will show a workflow for the meta-analysis of data from different experiment types and integration into pathway mining in order to gain new insights into biological mechanisms.
2:00 Chairperson’s Remarks
Victor Levenson, Ph.D., Associate Professor, Radiation Oncology and Pathology, Rush University Medical Center
2:05 Combinatorial Epigenetic Therapy Regiments for Ovarian Cancer
Kenneth P. Nephew, Ph.D., Professor of Medical Sciences; Cellular and Integrative Physiology; Obstetrics and Gynecology; Co-Director, Center for Integrated Cancer Biology; Assistant Director, Basic Science Research, Indiana University Simon Cancer Center
Altered epigenetic states are a hallmark of all cancers, including ovarian, the most lethal gynecologic malignancy. Epigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies, DNA methylation inhibitors, in combination with existing chemotherapeutics, have potential for overcoming acquired drug resistance, laying the foundation for this specific class of epigenetic drug in ovarian cancer clinical trials. Epigenetic drug effects on pharmacodynamic targets are beginning to emerge.
2:35 Development of DNA Methyltransferase Inhibitors for the Treatment of Neoplastic Diseases
Tamer E. Fandy, Ph.D., Research Fellow, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Re-expression of epigenetically silenced tumor suppressor genes is a rational strategy for the treatment of human neoplasms. Epigenetic modifiers like DNA methyltransferase (DNMT) inhibitors induce the re-expression of epigenetically silenced genes in vitro and in vivo.Ongoing clinical trials are attempting to identify tumor suppressor genes that upon re-expression can induce remission and cure in patients.On the other hand, recent reports demonstrate lack of association of methylation reversal and clinical response and suggest a complex mechanism of action.
3:05 ChIP-Seq Accurately Predicts Tissue-specific Activity of Enhancers
R. David Hawkins, Ph.D., Epigenome Center, University of California, San Diego
3:35 Networking Refreshment Break, Exhibit & Poster Viewing
4:15 A Blood-based Diagnostic Test for Pancreatic Cancer
Victor Levenson, Ph.D., Associate Professor, Radiation Oncology and Pathology, Rush University Medical Center
Presented will be the first report of a DNA methylation-based test with over 90% accuracy. This newly developed blood-based test differentiates pancreatic cancer and chronic pancreatitis. The test requires minimal amounts of blood, and can be completed within 24 hours. Further improvement is expected to bring the accuracy to 99%.
4:45 Panel Discussion
5:15 Close of Day