An investigation of Radial Glia as the source of Ependymoma Stem Cells

Information

  • Research Project
  • 9069142
  • ApplicationId
    9069142
  • Core Project Number
    R01CA129541
  • Full Project Number
    7R01CA129541-10
  • Serial Number
    129541
  • FOA Number
    PA-14-078
  • Sub Project Id
  • Project Start Date
    8/1/2015 - 9 years ago
  • Project End Date
    3/31/2017 - 7 years ago
  • Program Officer Name
    MIETZ, JUDY
  • Budget Start Date
    8/1/2015 - 9 years ago
  • Budget End Date
    3/31/2016 - 8 years ago
  • Fiscal Year
    2015
  • Support Year
    10
  • Suffix
  • Award Notice Date
    7/7/2015 - 9 years ago
Organizations

An investigation of Radial Glia as the source of Ependymoma Stem Cells

DESCRIPTION (provided by applicant): Ependymomas are tumors of the brain and spinal cord. Treatment approaches and mortality rates for this disease have changed little over the last twenty years, highlighting the great need for new therapies. Histologic similarities among ependymomas have led investigators to treat these tumors as a single entity; but we have shown that ependymomas from different regions of the central nervous system include discrete clinical and molecular subtypes, suggesting they are different diseases. Thus, contemporary efforts to cure all patients with ependymoma must be concerned with understanding the biological basis of these disease subtypes, and where necessary, developing subtype-specific therapies. During the last funding cycle we developed a cross- species genomics approach that characterized genomic subtypes of human ependymoma and matched these with neural stem cells in the mouse to generate accurate models of the disease. We will build on this work to complete three Specific Aims designed to test the central hypothesis that 'Ependymoma subtypes are driven by distinct cell signals that can be targeted for therapeutic gain.' Aim 1 will employ new 'virus-pool' screens to test the in vivo oncogenic role of the top 90 candidate oncogenes and 40 tumor suppressor genes that we previously identified in ependymoma. We will thereby generate a 'clinic' of mice that recapitulate the full spectrum on human ependymoma subtypes. Aim 2 will interrogate the models developed in Aim 1 using high- throughput drug screens, kinome-wide binding and cell biology assays to pinpoint the key cell signals that maintain each ependymoma subtype that might therefore serve as therapeutic targets. Integration of these data with genetic analyses of human and mouse tumors will further validate candidate drug targets. Future clinical trials of therapies that target signals identified in Aim 2 will demand the selection of patients with the appropriate disease subtype. Therefore, Aim 3 will develop a robust Affymetrix Quantigene assay to reliably and rapidly diagnose ependymoma subtypes using formalin fixed paraffin embedded tissue.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    R01
  • Administering IC
    CA
  • Application Type
    7
  • Direct Cost Amount
    147816
  • Indirect Cost Amount
    11825
  • Total Cost
    159641
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    393
  • Ed Inst. Type
  • Funding ICs
    NCI:159641\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    CNBT
  • Study Section Name
    Clinical Neuroimmunology and Brain Tumors Study Section
  • Organization Name
    UNIVERSITY OF CAMBRIDGE
  • Organization Department
  • Organization DUNS
    226552610
  • Organization City
    CAMBRIDGE
  • Organization State
  • Organization Country
    UNITED KINGDOM
  • Organization Zip Code
    CB2 1TN
  • Organization District
    UNITED KINGDOM