Core C: Genomics and High Throughput Screening Core

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This Core provides cutting edge tools that allow invesfigators to monitor cellular and molecular changes that occur during normal hematopoiesis or in pathological states associated with bone marrow failure (BMF), nonmalignant myelodysplastic syndromes or defects in erythropoiesis/megakaryopoiesis, addressing the three foci of this application as detailed in the OVERALL DESCRIPTION. There is a clear need for services to identify and analyze in a rapid, high throughput fashion drugs that influence hematopoiefic cell commitment to various lineages and to develop miniaturized systems for studies of stromal/niche environments. Dr. Diamond is the director of the University of Pennsylvania (UPENN) PCMD, which he established as a Core Facility in 2005 (see BIOSKETCH). Dr. Diamond has 20 years of experience with numerous projects in endothelial biology, blood biology, and blood systems biology. He already has been working with Drs. Poncz, French and Gadue on niche effects on thrombopoiesis from mature megakaryocytes. He will be overall Director and Director of SubCore C-1. Dr. Baldwin will direct the analysis of RNA and DNA changes in cells during hematopoiesis. He has 11 years of industrial and academic experience in microarray assays, serves on the Neuroscience Microarray Consortium Advisory Panel for the NIH, co-chairs the MicroArray Research Group of the Associafion of Biomolecular Resource Facilifies, and interacts regularly with core directors on a nafional level (see BIOSKETCH). Dr. Baldwin founded the Penn Microarray Facility in 2001, was appointed Director of the Molecular Diagnosis and Genotyping Facility in 2005, and has merged the two laboratories to create the Molecular Profiling Facility. He has conducted previous genomic profiling projects with Drs. Weiss, Blobel, Carroll, Diamond, Discher, Gewirtz, June and Pear on efforts directly relevant to this P30. We have combined components of the two UPENN cores run by Drs. Diamond and Baldwin to develop a single core for this P30 to incorporate state-of-the-art resources on our campus that will unite our abilities to analyze normal, pathologic and manipulated hematopoietic cells. SubCore C-1 offers high-throughput microscale screening for compounds that affect various aspects of hematopoiefic cell biology, including lineage commitment (either from embryonic stem (ES) cells or more differentiated progenitors), survival, proliferation or maturafion into mature blood cells. SubCore C-2 will analyze changes that occur in the RNA expression profiles and epigenetic DNA marks in these cells either de novo or after modifications using Core E. We believe that these two SubCores reflect a common theme of rapidly analyzing cells and cellular changes using complex methodologies with significant investment in rapidly changing equipment and technologies. Core C is committed to bringing the most current and innovative technologies to the P30 investigators, while providing campus-wide standardization of services to support cooperafive efforts by different invesfigators with complementary interests and expertise. Our goal is to provide significant labor-intensive service and guidance at very compefitive pricing, supported in part by efficiency of utilizafion and by UPENN financial support.