Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable brain tumor that arises in children. My laboratory is one of very few laboratories around the world that is studying DIPG biology using genetically engineered mouse modeling. This Independent Scientist Award will give me the opportunity to focus on research to dissect the mechanisms by which K27M histone mutations contribute to DIPG pathogenesis. Ultimately, this information will lay the groundwork for the identification of effective therapeutic agents to treat this incurable cancer.

Public Health Relevance

This Independent Scientist (K02) award will support Dr. Becher to use mouse genetics to study the mechanism by which K27M histone mutations contribute to diffuse intrinsic pontine glioma (DIPG) pathogenesis. These in vitro and vivo studies will provide a mechanistic foundation for the design of safe and effective therapies to treat this incurable brain cancer that arises in children.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02NS086917-02
Application #
8826199
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fountain, Jane W
Project Start
2014-09-01
Project End
2019-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
2
Fiscal Year
2015
Total Cost
$194,907
Indirect Cost
$14,438

  Institution

Name
Duke University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Hoeman, Christine; Shen, Chen; Becher, Oren J (2018) CDK4/6 and PDGFRA Signaling as Therapeutic Targets in Diffuse Intrinsic Pontine Glioma. Front Oncol 8:191
Hennika, Tammy; Hu, Guo; Olaciregui, Nagore G et al. (2017) Pre-Clinical Study of Panobinostat in Xenograft and Genetically Engineered Murine Diffuse Intrinsic Pontine Glioma Models. PLoS One 12:e0169485
Cordero, Francisco J; Huang, Zhiqing; Grenier, Carole et al. (2017) Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG. Mol Cancer Res 15:1243-1254
Hennika, Tammy; Becher, Oren J (2016) Diffuse Intrinsic Pontine Glioma: Time for Cautious Optimism. J Child Neurol 31:1377-85
Misuraca, Katherine L; Hu, Guo; Barton, Kelly L et al. (2016) A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells. Neoplasia 18:60-70
Subashi, Ergys; Cordero, Francisco J; Halvorson, Kyle G et al. (2016) Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma. J Neurooncol 126:243-51