Join Now

Project Details
  • Title: Therapeutic modulation of the methyl-CpG-binding domain protein 2 (MBD2) in glioma
  • Date Proposed: 09/21/2009
  • Amount Requested: $200,000.00
  • Amount we Paid: $0.00
  • Stauts: Approved - Waiting For Funding
  • Research name: Erwin Van Meir
  • Hospital: 200000
  • Grey Ribbon Crusade Participants:
    • Musella Foundation For Brain Tumor Research & Information, Inc
  • Simple Description: The overall purpose of the present project is to explore a new therapy for glioblastoma multiforme (GBM). One of GBM’s most characteristic features is structurally and functionally abnormal angiogenesis. The critical endogenous angiogenesis inhibitors in the brain remain to be identified. Brain angiogenesis inhibitor 1 (BAI1) is a 170-kDa seven transmembrane G protein receptor specifically expressed in the brain. It has a large (120 kDa) extracellular domain (Vasculostatin), which contains an RGD integrin binding motif and five thrombospondin type 1 repeats (TSR), domains known to have anti-angiogenic properties. Our previous results demonstrated that BAI1 may be functioning as an antiangiogenic tumor suppressor gene, which suggests that restoration of BAI1 gene function in brain tumors might be of therapeutic value. BAI1 is specifically expressed in normal brain parenchyma but is absent in most human GBM samples. Our preliminary data indicated that CpG islands in the BAI1 gene promoter were aberrantly methylated in human GBM samples. We found that BAI1 expression could be reactivated by treatment of DNA methylaton inhibitors. Moreover, we found that methyl-CpG-binding domain (MBD) protein 2 (MBD2) specifically binds to the BAI1 gene promoter, and its knockdown by RNA interference or treatment with MBD2 inhibitors (Collaboration with Dr. William G. Nelson, John Hopkins University) reactivates BAI1 expression. Based on our results, we hypothesize that MBD2 mediates the epigenetic silencing of BAI1 and thereby, MBD2 may represent a novel therapeutic target in human gliomas. Request is for $100,000 a year for 2 years.