2019 Fiscal Year Final Research Report

Identification of abnormal cellular signals and clinical targets rerated to the various pathology of neurofibromatosis

Research Project

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Project/Area Number	16H05440
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Neurosurgery
Research Institution	Kumamoto University
Principal Investigator	araki norie 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
Co-Investigator(Kenkyū-buntansha)	尹浩信熊本大学, 大学院生命科学研究部(医), 教授 (20282634) 中村英夫久留米大学, 医学部, 准教授 (30359963)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	神経線維腫症 / NF1 / NF2 / 融合オミクス / シグナルトランスダクション
Outline of Final Research Achievements	Neurofibromatosis (NF) is an autosomal dominant disease that predisposes individuals to developing various phenotypes including neural tumors with unknown mechanism being difficult to cure. In this study, to elucidate the mechanism of development of various tumor pathologies related to this disease and to develop therapeutic targets, we established NF model cells from NF gene-deficient patient tumors and NF-KD tumor (stem) cells, and subjected to a unique integrated-omics system using our original software iPEACH/ MANGO plus. As the results of extracting specific networks using these cells, novel NF specific signal networks related to the anti-apoptosis, complex molecules of the protein translation extension, and growth regulation signalings were identified. After several validations, we demonstrate that these signal molecules could be novel therapeutic targets and useful for the development of curatives against NF related tumors.
Free Research Field	腫瘍医学
Academic Significance and Societal Importance of the Research Achievements	神経線維腫症(NF)は、1991-1994年に原因遺伝子NF1/2が同定された。NF1は頻度の高さ(1/3000)から、NF２は脳神経系病態の深刻さから、これらの多彩な発病機構の解明とその治療法・治療薬の開発が大きく望まれているが、現在まで成功していない。ユニークに構築されたNF遺伝子変異／欠失病態モデル細胞を用いて、これらの細胞内で特異的に活性化するシグナル分子群の同定を目的として、独自開発による融合オミクスによって大規模分子解析を行い、特異的な治療標的となる候補分子群を世界で初めて同定した。この成果は根治療不可能である本疾患の治療法・薬剤開発に重要な基礎情報として貢献できる可能性が高い。