Carolina Cardiopulmonary Gene Expression Services

Summary

Principal Investigator: C Patterson
Abstract: Over time, the primary determinant of cellular phenotypes is the pattern of genes that are expressed. For the past two decades, gene expression has been analyzed on a gene-by-gene basis in order to explain the cell biology, heredity, and pathophysiology of cardiopulmonary diseases. More recently, the advent of new technologies - especially DNA microarrays - has allowed scientists to shift their focus from single genes to patterns of gene expression that can be analyzed using computation methods. These technologic advances have been enormously instructive over the past 2-3 years, particularly in the field of tumor biology. Although there are, if anything, even more applications for these technologies in the cardiopulmonary sciences, technological and financial barriers have limited the ability of NHLBI-funded investigators to apply these methods. These barriers are particularly acute at UNC, where the NHLBI-funded investigators have limited resources to apply DNA microarrays to the scientific and medical problems they are studying. In this application, we propose to establish the Carolina Cardiopulmonary Gene Expression Services to serve the microarray needs of NHLBI-funded investigators at UNC in the Carolina Cardiovascular Biology Center, the Cystic Fibrosis Center, and the Center for Thrombosis and Hemostasis. These centers encompass the major mission areas of NHLBI. We propose to take advantage of the expertise in microarray technology that has been assembled by the Lineberger Comprehensive Cancer Center at UNC, and apply this same technology to areas of interest to NHLBI. An Internal Operations Committee has been assembled to oversee the establishment and implementation of this service, to determine how access to NHLBI-funded investigators is allocated, and to ensure that issues of experimental design, quality control, and bioinformatic analysis are rigorous. This committee will also be charged to determine that the NHLBI-sponsored gene expression services remain state-of-the-art, by monitoring advances in technologies by other laboratories as well as by supporting technological advances by local scientists. The present proposal has four aims: Aim #1: Capital expansion of microarray services for UNC NHLBI-funded investigators; Aim #2: Technology expansion of UNC microarray services; Aim #3: Bioinformatics services for UNC NHLBI-funded microarray users; and Aim #4: Microarray applications in cardiopulmonary biology. These aims will support our overall goal to provide NHLBI-funded investigators at UNC with comprehensive microarray services that complement their existing research programs; we anticipate that the unified nature of our services will permit scientific and technological advances that will benefit the larger cardiopulmonary community.
Funding Period: 2002-09-30 - 2007-07-31
more information: NIH RePORT

Top Publications

  1. ncbi ERK signaling is a central regulator for BMP-4 dependent capillary sprouting
    Qian Zhou
    Department of Cardiology, University of Freiburg, Freiburg, Germany
    Cardiovasc Res 76:390-9. 2007
  2. pmc SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration
    Xinchun Pi
    Carolina Cardiovascular Biology Center and Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 106:5675-80. 2009
  3. pmc A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling
    Rusty Kelley
    Department of Medicine, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 184:597-609. 2009
  4. pmc Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors
    Xinchun Pi
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 179:1569-82. 2007
  5. pmc Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins
    Hui Hua Li
    Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7126, USA
    J Clin Invest 117:3211-23. 2007
  6. ncbi Gene expression profile signatures indicate a role for Wnt signaling in endothelial commitment from embryonic stem cells
    Hong Wang
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, USA
    Circ Res 98:1331-9. 2006
  7. pmc PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation
    Yaxu Wu
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599 7126, USA
    J Mol Cell Cardiol 44:47-58. 2008
  8. pmc ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism
    James E Ferguson
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
    Mol Cell Biol 27:6407-19. 2007
  9. pmc BMPER is a conserved regulator of hematopoietic and vascular development in zebrafish
    Martin Moser
    University of Freiburg, Internal Medicine III, Hugstetter Strasse 55, 79106 Freiburg, Germany
    J Mol Cell Cardiol 43:243-53. 2007
  10. pmc Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses
    Rongqin Ren
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill 27599 7126, USA
    Blood 109:2847-53. 2007

Scientific Experts

  • C Patterson
  • Martin Moser
  • Hui Hua Li
  • Yaxu Wu
  • Hong Wang
  • Xinchun Pi
  • Rongqin Ren
  • James E Ferguson
  • Peter C Charles
  • Rusty Kelley
  • Jonathan C Schisler
  • Qian Zhou
  • Chunlian Zhang
  • Liliana Attisano
  • Malcolm Ross
  • Samuel S Wu
  • Isabel Moreno
  • Sabeen Mapara
  • Joel S Parker
  • George A Stouffer
  • Dane Meredith
  • Monte Willis
  • Andrea L Portbury
  • Monika Podkowa
  • Eleanor G Hilliard
  • Brian D Alder
  • Robert E Lineberger
  • Holly McDonough
  • Hengbin Wang
  • James Meeker
  • Da Zhi Wang
  • Richard E Cheney
  • Victoria L Bautch
  • Kyle Powers
  • Alberto Vargas
  • Christoph Bode
  • Aparna B Bohil
  • Jennifer B Gilner
  • Suzanne L Kirby
  • Russell Kelley
  • Tobias Krauss
  • Kevin Smith
  • Stephan Winnik
  • Peter Charles
  • Melinda Divito
  • Brandon J Wainwright
  • Jennifer Heinke
  • Victoria Bautch
  • Charles Perou
  • Jeffrey S Rubin
  • Michal Barshishat-Kupper

Detail Information

Publications12

  1. ncbi ERK signaling is a central regulator for BMP-4 dependent capillary sprouting
    Qian Zhou
    Department of Cardiology, University of Freiburg, Freiburg, Germany
    Cardiovasc Res 76:390-9. 2007
    ....
  2. pmc SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration
    Xinchun Pi
    Carolina Cardiovascular Biology Center and Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 106:5675-80. 2009
    ..In addition, the discovery of this interactive network of pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases...
  3. pmc A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling
    Rusty Kelley
    Department of Medicine, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 184:597-609. 2009
    ..This dosage-dependent molecular switch resolves discordances among studies that examine how Bmper regulates Bmp activity and has broad implications for Bmp signal regulation by secreted mediators...
  4. pmc Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors
    Xinchun Pi
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 179:1569-82. 2007
    ..Our data indicate that Myo10 is required to guide endothelial migration toward BMP6 gradients via the regulation of filopodial function and amplification of BMP signals...
  5. pmc Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins
    Hui Hua Li
    Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7126, USA
    J Clin Invest 117:3211-23. 2007
    ....
  6. ncbi Gene expression profile signatures indicate a role for Wnt signaling in endothelial commitment from embryonic stem cells
    Hong Wang
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, USA
    Circ Res 98:1331-9. 2006
    ..These data indicate a requisite and ongoing role for Wnt activity during vascular development, and the gene expression profiles identify candidate components of this pathway that participate in vascular cell differentiation...
  7. pmc PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation
    Yaxu Wu
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599 7126, USA
    J Mol Cell Cardiol 44:47-58. 2008
    ....
  8. pmc ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism
    James E Ferguson
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA
    Mol Cell Biol 27:6407-19. 2007
    ..We postulate that hydroxylation of ASB4 in normoxia promotes binding to and degradation of substrate protein(s) to modulate vascular differentiation...
  9. pmc BMPER is a conserved regulator of hematopoietic and vascular development in zebrafish
    Martin Moser
    University of Freiburg, Internal Medicine III, Hugstetter Strasse 55, 79106 Freiburg, Germany
    J Mol Cell Cardiol 43:243-53. 2007
    ..The generation of the caudal vein is compromised and the pattern guiding of the intersomitic vessels is disturbed, indicating that zbmper is required for early steps in vascular pattern formation and hematopoiesis in zebrafish...
  10. pmc Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses
    Rongqin Ren
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill 27599 7126, USA
    Blood 109:2847-53. 2007
    ..These data indicate that Cox2 may serve as a unifying component downstream from disparate pathways to modulate angiogenic responses in diseases in which neovascularization plays an underlying pathophysiologic role...
  11. ncbi Wnt2 coordinates the commitment of mesoderm to hematopoietic, endothelial, and cardiac lineages in embryoid bodies
    Hong Wang
    Carolina Cardiovascular Biology Center and Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 282:782-91. 2007
    ....
  12. pmc Stable patterns of gene expression regulating carbohydrate metabolism determined by geographic ancestry
    Jonathan C Schisler
    McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, USA
    PLoS ONE 4:e8183. 2009
    ....