Pediatric astrocytomas are the most common form of brain cancer in children. This POI is designed to improve our understanding ofthe pathways that regulate these tumor cells and the environment in which such cells reside, and thereby to develop new therapeufic approaches. The Innovative Neuropathology (INP) Core seeks to facilitate this research through the following specific aims: 1. To generate and characterize primary pediatric astrocytoma cell lines and fissue resources. 2. To provide expert neuropathologic and molecular pathologic analysis of human and mouse astrocytoma models. 3. To develop innovative technologies for cellular and molecular characterizafion of pediatric astrocytomas and cell lines. 4. To ensure that tumor samples are used and analyzed in a stafisfically rigorous and efficient fashion. Given that the research of each project is heavily based upon the in vivo biology of human and mouse astrocytomas, the INP Core services focus on development and delivery of in vivo technologies such as immunohistochemistry, in situ hybridization, fluorescent in situ hybridization (FISH) for genomic aberrations, and genome wide technologies for studies in human tumors. In addition, the INP Core will work to improve emerging fissue technologies to enable analysis of small tumor samples and so conserve these rare tissue resources. In time these innovafions can lead to clinical tests that identify pafients who might benefit from particular targeted therapies (e.g. BRAF expression signatures that allow rapid screening for tumor samples likely to have BRAF mutafions). The centralized nature ofthe INP Core will foster intellectual resource sharing and allow investigators to accurately compare and interpret their findings within the spectrum of research performed across all the projects. The INP Core has the requisite neuropathologic expertise, biostatisfical knowledge, sophisticated resources, and experienced staff to carry out these aims and ensure that the POI meets its overall goals to improve our understanding of pediatric astrocytomas.
Pediatric brain tumors are one of the most common solid tumors in children. Targeted therapies are needed to both control the tumor and avoid the long term effects of current treatments. The Innovative Neuropathology Core seeks to support the Projects in discovery of the pathways that control growth of pediatric astrocytomas and in development of innovafive genefic technologies that can identify particular patients who might benefit from therapies against these pathways.
|Bechet, Denise; Gielen, Gerrit G H; Korshunov, Andrey et al. (2014) Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas. Acta Neuropathol 128:733-41|
|Francis, Joshua M; Zhang, Cheng-Zhong; Maire, Cecile L et al. (2014) EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov 4:956-71|
|Fontebasso, Adam M; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy et al. (2014) Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet 46:462-6|
|Chudnovsky, Yakov; Kim, Dohoon; Zheng, Siyuan et al. (2014) ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell Rep 6:313-24|
|Bergthold, Guillaume; Bandopadhayay, Pratiti; Bi, Wenya Linda et al. (2014) Pediatric low-grade gliomas: how modern biology reshapes the clinical field. Biochim Biophys Acta 1845:294-307|
|Sevenich, Lisa; Bowman, Robert L; Mason, Steven D et al. (2014) Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat Cell Biol 16:876-88|
|Liu, Xiaohui; Ide, Jennifer L; Norton, Isaiah et al. (2013) Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci Rep 3:2859|
|Stevens, Michael; Cheng, Jeffrey B; Li, Daofeng et al. (2013) Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods. Genome Res 23:1541-53|
|Ramkissoon, Lori A; Horowitz, Peleg M; Craig, Justin M et al. (2013) Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. Proc Natl Acad Sci U S A 110:8188-93|
|Katz, S G; Fisher, J K; Correll, M et al. (2013) Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK. Oncogene 32:4078-85|
Showing the most recent 10 out of 13 publications