7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
8:45 KEYNOTE PRESENTATIONPersonalized Medicine and Public Health: Can GWAS be Brought to Standard of Care in Type 2 Diabetes? Eric P. Hoffman, Ph.D., Director, Research Center for Genetic Medicine, Children's National Medical Center
Genome-wide association studies (GWAS) have identified polymorphisms that confer risk for type 2 diabetes. The CDC has published that 45% of children born in 2000, will develop type 2 DM and lose 20 years of life. This is a rapidly emerging health crisis, and is at the interface of lifestyle (diet, exercise), genetic predispositions, and personalized health. This presentation addresses both the potential advantages of included genotyping with lifestyle modification, and the challenges facing implementation on a public health scale.
9:30 Genome-Wide Profiling of the Estrogen Response in Breast Cancer Through a Cistrome Integrative ApproachMathieu Lupien, Ph.D., Department of Medical Oncology, Harvard Medical SchoolEstrogen signaling through the estrogen receptor alpha (ERa) is fundamental to the development and progression of over two-thirds of breast cancers. Using a genome-wide ChIP-on-chip approach, we report the integrative analysis of the cistromes for ERa as well as other components of the transcriptional response to estrogens, namely the pioneer factor FoxA1, the coactivator CARM1 and RNA Polymerase II. This reveals the functional implication of coactivator activity in defining the active ERa cistrome.
10:00 Morning Coffee
10:20 Tiling Array Analysis of DNA Copy Number VariationHerbert Auer, M.S., Director of the Functional Genomics Core, Institute for Research in Biomedicine
New research has shown that a significant portion of the genome can vary in the number of copies of DNA elements and that this copy number variation (CNV) contributes substantially to genotypic and phenotypic variation between individuals. The presentation describes the first-time usage of tiling arrays to measure CNVs at an unprecedented 35 base pair resolution across the entire genome. Comparison of normal individuals provides information about CNVs at a resolution two orders of magnitude better than any of the currently used microarray platforms. This method can be applied to a broad range of organisms, including human, mouse, rat, arabidopsis etc., where tiling arrays are commercially available.
10:50 Common Gene Copy Number Variations in Health and DiseaseYee Ling Wu, The Research Institute at the Nationwide Children’s Hospital, Ohio State UniversityResults of microarray experiments reveal that many genomic loci in mammals manifest frequent copy number variations (CNVs) among different individuals. Some of these CNV loci appear to be modular or segmental and involve multiple contiguous genes, with discrete and continuous variation in copy numbers. Gene copy number variation is an important mechanism contributing to quantitative traits and phenotypic diversities. Accurate and sensitive detection of CNV is essential for genetic and mechanistic studies of complex diseases. This talk will present specific examples to elucidate complex CNVs and their associations with human autoimmune diseases.
11:20 A Musical Score for DiseaseGil Alterovitz, Ph.D., Research Fellow, Harvard Medical School
11:50 Close of Session
INTEGRATIVE GENOMIC APPROACHES
2:00 Chairperson’s RemarksShelley Ann Des Etages, Ph.D., Senior Principal Scientist, Genetic Technologies, Pfizer Inc.
2:05 Harnessing Epigenomics for Personalized Diagnosis and Therapy of Acute LeukemiasMaria Eugenia Figueroa, M.D., Research Associate, Department of Hematology and Oncology, Weill Cornell Medical College
We propose the use of an integrative genomic and epigenomic approach for the study of acute myeloid leukemias. We have developed an integrative platform using high density oligonucleotide microarrays and have optimized the techniques for their use in routine human bone marrow samples obtained within the context of clinical trials. By combining epigenomic information (DNA methylation and histone modifications) we are capable of enhancing the biological information captured, thus revealing clinically relevant leukemia subtypes that were missed by the use of gene expression profiling alone.
2:35 Prognostic Multigene Expression Classification of Neuroblastoma Patients: a Route for SuccessJo Vandesompele, Ph.D., Professor, Center for Medical Genetics, Ghent University HospitalKey components of the strategy are the testing of many more patients than genes, rigorous RNA quality control, thorough evaluation of qPCR gene expression assays, use of absolute standards for cross-laboratory comparison, and application of a pre-amplification procedure enabling the profiling using only 20 ng of total RNA as starting material. Following the outlined strategy, we established a robust and accurate prognostic multigene expression predictor, suitable for routine lab tests and ready to be evaluated in prospective studies.3:05 Use of Genomic Platforms to Identify and Verify Modulation of Biomarkers in a Preclinical ModelStephen Tirrell, Ph.D., Director of Molecular Technology, Millennium Pharmaceuticals Inc.We have utilized microarrays and RT-PCR platforms to measure changes in gene transcript expression in model systems pre and post treatment. These platforms have been effective in identifying biomarkers using an in-vitro system. The in-vitro observations also have been verified with genomic and protein based assay in an in-vivo model system. This study will review the results and technologies used to select biomarkers with potential clinical applications.
3:35 Refreshment Break
4:00 Validation of Rat Reference Genes for Improved Quantitative Gene Expression Analysis using Low Density ArraysJenny Hon Cai, M.D., Infectious Disease, Pfizer Global Research & Development
Real-time PCR has become increasingly important in gene expression profiling research, and it is widely agreed that normalized data are required for accurate estimates of messenger RNA (mRNA) expression. With increased gene expression profiling in preclinical research and toxicogenomics, a need for reference genes in the rat has emerged. This presentation will describe an evaluation of commonly used housekeeping genes among various rat tissues for gene expression analysis in quantitative real-time RT-PCR using Low Density Arrays. The work will provide the useful tools for researchers to considerably enhance their research abilities to simply and efficiently identify appropriate reference genes for given experiments.
4:30 Study the Effects of Prenatal Factors on the Fetus Using MicroarraysNaveed Hussain, M.D., Associate Professor of Pediatrics, University of Connecticut School of Medicine
This presentation will examine the effects of prenatal tobacco exposure on mRNA expression in umbilical cord tissue using gene microarrrays. Tobacco smoke contains more than 4,000 chemicals, including carcinogens and mutagens, which either alone or in combination may influence gene expression. Since the umbilical cord is exclusively fetal tissue, it provides a unique opportunity to examine effects of prenatal (tobacco) exposure on the fetal biological system. Based on the magnitude of up-regulation or down-regulation of messenger RNA expression, the most differentially regulated genes in fetal tissue in relation to maternal smoking were identified. These findings provide insight into potential processes by which the fetus adapts to the adverse effects of maternal smoking and may help to understand how smoking during pregnancy may be responsible for changes that predispose to adult diseases.
5:00 Panel Discussion with Afternoon SpeakersModerator: Shelley Ann Des Etages, Ph.D., Pfizer Inc.
5:30 Grand Opening of Exhibit Hall
7:00 Close of Day
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