This Core provides cutting edge tools that allow investigators 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 hematopoietic 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 Association of Biomolecular Resource Facilities, and interacts regularly with core directors on a national 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 hematopoietic cell biology, including lineage commitment (either from embryonic stem (ES) cells or more differentiated progenitors), survival, proliferation or maturation 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 cooperative efforts by different investigators with complementary interests and expertise. Our goal is to provide significant labor-intensive service and guidance at very competitive pricing, supported in part by efficiency of utilization and by UPENN financial support.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK090969-05
Application #
8698737
Study Section
Special Emphasis Panel (ZDK1-GRB-G)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
$198,837
Indirect Cost
$79,322
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Cheng, Ying; Chikwava, Kudakwashe; Wu, Chao et al. (2016) LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors. J Clin Invest 126:1267-81
Dingal, P C Dave P; Bradshaw, Andrew M; Cho, Sangkyun et al. (2015) Fractal heterogeneity in minimal matrix models of scars modulates stiff-niche stem-cell responses via nuclear exit of a mechanorepressor. Nat Mater 14:951-60
Reeves, D A; Gu, B W; Bessler, M et al. (2015) Variations in reactive oxygen species between mouse strains. Blood Cells Mol Dis 55:189-90
Byrska-Bishop, Marta; VanDorn, Daniel; Campbell, Amy E et al. (2015) Pluripotent stem cells reveal erythroid-specific activities of the GATA1 N-terminus. J Clin Invest 125:993-1005
Sosale, Nisha G; Rouhiparkouhi, Tahereh; Bradshaw, Andrew M et al. (2015) Cell rigidity and shape override CD47's "self"-signaling in phagocytosis by hyperactivating myosin-II. Blood 125:542-52
Rozenova, Krasimira; Jiang, Jing; Donaghy, Ryan et al. (2015) MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling. Blood 125:1730-8
Jain, Deepti; Mishra, Tejaswini; Giardine, Belinda M et al. (2015) Dynamics of GATA1 binding and expression response in a GATA1-induced erythroid differentiation system. Genom Data 4:1-7
Ivanovska, Irena L; Shin, Jae-Won; Swift, Joe et al. (2015) Stem cell mechanobiology: diverse lessons from bone marrow. Trends Cell Biol 25:523-32
Sosale, Nisha G; Spinler, Kyle R; Alvey, Cory et al. (2015) Macrophage engulfment of a cell or nanoparticle is regulated by unavoidable opsonization, a species-specific 'Marker of Self' CD47, and target physical properties. Curr Opin Immunol 35:107-12
Spinler, Kyle R; Shin, Jae-Won; Lambert, Michele P et al. (2015) Myosin-II repression favors pre/proplatelets but shear activation generates platelets and fails in macrothrombocytopenia. Blood 125:525-33

Showing the most recent 10 out of 45 publications