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Dissect regulation of RNA translation in human cancers

Dissect regulation of RNA translation in human cancers
剖析人类癌症中 RNA 翻译的调控
批准号:
9307739
负责人:
Zhe Ji
金额:
$9.99万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2017-12-31

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中文摘要
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英文摘要
PROJECT SUMMARY Studies have shown that RNA translation plays important regulatory roles during oncogenic transformation, cancer progression and metastasis. Targeting RNA translation for cancer therapy has enormous potential. However, translational regulation during oncogenesis in the genome-wide basis remains largely unexplored, as most current cancer research still focuses on transcriptome. Here I propose to use an integrated experimental and computational genomics approach to systematically dissect the regulation of RNA translation and the functional roles of translation factors in human cancers. Aim 1 will examine genome-wide regulation of mRNA translation during oncogenic transformation mediated by various oncogenes and tumor suppressor genes. The result will reveal novel mechanisms and functional targets of translational regulation underlying oncogenic transformation and cancer heterogeneity. Aim 2 will study the functional roles of translation factors and their genome-wide targets during oncogenic transformation. The study will provide mechanistic insights for targeting translation factors for cancer therapy. Aim 3 will characterize the regulation of RNA translation and gene co- expression networks of translation factors in human cancer patient samples using proteomics and transcriptomics data from the Cancer Genome Atlas (TCGA) database. This analysis will show how the regulatory mechanisms discovered using the cancer cell line models in Aims 1 and 2 contribute to in vivo cancer progression and heterogeneity. Taken together, the proposed experiments will systematically dissect the functional roles and genome-wide targets of translational regulation and translation factors in human cancers. The results will provide a novel mechanistic basis for targeting RNA translation in cancer therapy. While I have received extensive interdisciplinary training in computational genomics, cancer biology and molecular biology, the K99/R00 award will help me develop experimental skills, including implementing next- generation sequencing technologies based and molecular biology techniques. The research will take advantage of the unique and complementary expertise of the principal investigator, my mentors (Dr. Kevin Struhl at Harvard Medical School and Dr. Aviv Regev at the Broad Institute of MIT and Harvard) and my collaborator (Dr. Jean Zhao at Dana Farber Cancer Institute). Harvard Medical School and the Broad Institute provide me with an exceptional training environment. The proposed research will facilitate my career development to be an independent scientific investigator working at the forefront of cancer systems biology and developing novel therapeutic strategies for human cancers.
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会议论文
An ultra-low-input RNase footprinting assay to quantify cytosolic and mitochondrial translation simultaneously
An ultra-low-input RNase footprinting assay to quantify cytosolic and mitochondrial translation simultaneously
Characterizing functional translation in putative 'noncoding' regions of a genome
Characterizing functional translation in putative 'noncoding' regions of a genome
国内基金
海外基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号:
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  • 项目类别:
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  • 依托单位:
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  • 项目类别:
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  • 资助金额:
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  • 批准年份:
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  • 项目类别:
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  • 资助金额:
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  • 批准年份:
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  • 负责人:
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  • 依托单位: