Targeting MACF1 in Glioblastoma

Information

  • Research Project
  • 9977206
  • ApplicationId
    9977206
  • Core Project Number
    SC3GM121178
  • Full Project Number
    5SC3GM121178-04
  • Serial Number
    121178
  • FOA Number
    PAR-14-018
  • Sub Project Id
  • Project Start Date
    8/1/2017 - 7 years ago
  • Project End Date
    7/31/2021 - 3 years ago
  • Program Officer Name
    KRASNEWICH, DONNA M
  • Budget Start Date
    8/1/2020 - 4 years ago
  • Budget End Date
    7/31/2021 - 3 years ago
  • Fiscal Year
    2020
  • Support Year
    04
  • Suffix
  • Award Notice Date
    7/29/2020 - 4 years ago

Targeting MACF1 in Glioblastoma

PROJECT SUMMARY/ABSTRACT The specificity of current chemo- and radiation therapy protocols used to treat clinical glioblastomas while sparing normal cells and tissues has remained a caveat for therapeutic treatments of this disease. This issue is compounded by the subtypes of glioblastoma with varying genetic profiles, making it necessary to identify novel uncharacterized therapeutic targets in these cancers. The utility of a targeted therapy approach therefore offers greater clinical benefit over standard clinical treatment modalities because of its selectivity and specificity. A targeted therapy approach is particularly advantageous for the treatment of malignant brain tumors as a means to circumvent the cellular and molecular heterogeneity of these tumors which contribute to their high rates of recurrence and therapeutic resistance. Like most human cancers the invasive nature and continued propagation of glioblastoma are governed by cytoskeletal proteins. The objective of this study is to assess Microtubule Actin Cross-Linking Factor (MACF1), a cytoskeletal integrator protein, for its role in glioblastoma. Evaluation of MACF1 as a therapeutic target in malignant brain tumors is based on preliminary data from the proposed work that supports the hypothesis that MACF1 contributes to the maintenance and progression of malignant brain tumors and will be addressed with two specific aims: 1) To ascertain MACF1 as an inhibitory target and its tumorigenic role in glioblastoma and 2) To evaluate inhibitory targeting of MACF1 as a chemosensitizer in glioblastoma. Genetic inhibitory and overexpression experiments will be used to assess anti-tumorigenic targeting and tumorigenic properties of MACF1 in glioblastoma, while biomarker expression analysis of MACF1 will be performed on various gliomas from patients. Further the effects of silencing MACF1 function will be evaluated as a sensitizer of the chemotherapeutic agent, temozolomide. The proposed research is both innovative and significant because antagonizing MACF1 function provides a single target that will impair properties of two distinct populations of proliferating and migratory invasive cells that contribute to the perpetuation and recurrence of glioblastoma; as well as identify an uncharacterized target that expands our approach to combating not only glioblastoma but other cancers that will be diagnosed in 1 out 2 persons during their lifetime.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    SC3
  • Administering IC
    GM
  • Application Type
    5
  • Direct Cost Amount
    75000
  • Indirect Cost Amount
    31500
  • Total Cost
    106500
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIGMS:106500\
  • Funding Mechanism
    OTHER RESEARCH-RELATED
  • Study Section
    ZGM1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    TENNESSEE STATE UNIVERSITY
  • Organization Department
    BIOLOGY
  • Organization DUNS
    108814179
  • Organization City
    NASHVILLE
  • Organization State
    TN
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    372091561
  • Organization District
    UNITED STATES