Investigating microRNA miR-34a in lung cancer development and therapy

研究 microRNA miR-34a 在肺癌发展和治疗中的作用

基本信息

批准号：
8901573
负责人：
Wen Xue
金额：
$ 24.9万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901573
关键词：
Area Award Bioinformatics Biological Biological Process Biology Cancer Model Cancer Prognosis Cell Aging Cell Proliferation Cell Survival Cells Collaborations Communities Data Data Set Databases Development Doxycycline Educational workshop Environment Family Fostering Foundations Gene Expression Profiling Gene Targeting Genes Genetic Goals Human Institutes Intention Laboratories Lung Lung Neoplasms Maintenance Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of lung Mediating Mediator of activation protein Mentors MicroRNAs Modeling Molecular Monitor Mouse Cell Line Mus NF-kappa B Nanotechnology Pathway interactions Patients Phenotype Play Postdoctoral Fellow Protein p53 Publishing Recruitment Activity Research Research Project Grants Sampling Seeds Shapes Small Interfering RNA Solid Staging Students System Technology Therapeutic Agents Therapeutic Effect Training Treatment Efficacy Tumor Suppression Tumor Suppressor Genes Tumor Suppressor Proteins Tumor Volume Untranslated Regions Work abstracting anticancer research cancer cell cancer gene expression cancer therapy career experience human cancer mouse model in vivo in vivo Model inhibitor/antagonist interest medical schools molecular phenotype mouse model nanomaterials nanoparticle neoplastic cell novel novel strategies programs research study restoration skills small hairpin RNA therapy development tumor tumor initiation tumor progression undergraduate student

项目摘要

Project Summary/Abstract My research is focused on elucidating the cellular and molecular mechanisms that microRNAs play in cancer. microRNA (miRNA) molecules have emerged as important regulators of many biological processes, including cancer. It is known that many tumor suppressor miRNAs are lowly-expressed in cancer. However, the ability of these miRNAs to restrain tumor progression and whether miRNAs can be therapeutically delivered to treat cancer is not well established in in vivo models. The project proposed within this K99/R00 award outlines the creation and implementation of novel conditional miRNA expression system, nano-particle delivery system, and miRNA target identification pipelines that allow studying microRNA in mouse and human cancer models. The research proposed within this application has been shaped by my experiences studying p53 tumor- suppressor gene restoration, identifying tumor suppressors in liver cancer, performing in vivo shRNA screen, and by my recent efforts to elucidate the therapeutic effects of NF-kB inhibitors in lung cancer. These research projects solidified my interests in pursuing a career studying the fundamental biology of tumor suppressor miRNA in human cancer progression and therapy because miRNAs like miR-34 are emerging mediators of important tumor suppressive pathways. The systems that we propose herein utilize autochthonous mouse models and genetically defined human cancer cells. This study will integrate genetics, bioinformatics and translational nano-technology to study miR-34's function in lung cancer development and evaluate miR-34 family as a potential therapeutic agent for lung cancer. The facilities at the Koch Institute at MIT, and the expertise that my mentor, Dr. Jacks, can provide will be invaluable for successful implementation of this project. The goals of these experiments outlined within are: · Elucidating the mechanisms by which miR-34a inhibits lung tumor progression · Develop nano-technology to systematically deliver miR-34a in mouse and human lung tumor models · Identify and validate novel miR-34a target genes relevant to human lung cancer The research environment in the Jacks Laboratory, MIT, and the surrounding area offers unmatched opportunities for scientific discussion, collaboration, and training. Currently, I supervise an undergraduate student and a technical assistant that work directly with me on experiments pertaining to my research. This is an incredible experience that will endow me with many of the necessary skills to manage an independent laboratory. The scientific community at MIT, the Broad Institute, and Harvard Medical School offers countless seminars and workshops that will continue to foster my scientific development. My immediate goals are to develop the research platform described in this application and to demonstrate its potential to uncover molecular and cellular mechanisms of miR-34a and other tumor suppressor miRNAs. It is my intention to start an independent research program that will capitalize on these in vivo systems by studying tumor-suppressor miRNAs in a variety of tumor models. For the long-term, I am confident that these experiments will provide a solid foundation on which my research program can be built upon. I look forward to educating and recruiting students and postdocs that share my passion for cancer research.

项目概要/摘要我的研究重点是阐明 microRNA 发挥作用的细胞和分子机制 microRNA (miRNA) 分子已成为许多生物过程的重要调节因子，众所周知，许多肿瘤抑制 miRNA 在癌症中低表达。这些 miRNA 抑制肿瘤进展的能力以及 miRNA 是否可以用于治疗 K99/R00 中提出的用于治疗癌症的项目尚未在体内模型中得到很好的证实。该奖项概述了新型条件 miRNA 表达系统纳米颗粒的创建和实施递送系统和 miRNA 靶标识别管道，可用于研究小鼠和人类的 microRNA 癌症模型。本申请中提出的研究是根据我研究 p53 肿瘤的经验而形成的—— 抑制基因修复，鉴定肝癌中的抑癌基因，进行体内shRNA筛选，我最近努力阐明 NF-kB 抑制剂对肺癌的治疗作用。项目巩固了我从事肿瘤抑制基础生物学研究职业的兴趣 miRNA 在人类癌症进展和治疗中的作用，因为像 miR-34 这样的 miRNA 是新兴的介质我们提出的系统利用了本地小鼠。这项研究将整合遗传学、生物信息学和基因定义的人类癌细胞。转化纳米技术研究 miR-34 在肺癌发展中的功能并评估 miR-34 麻省理工学院科赫研究所的设施和我的导师 Jacks 博士可以提供的专业知识对于成功实施这一计划非常宝贵项目。其中概述的这些实验的目标是： · 阐明miR-34a抑制肺肿瘤进展的机制 · 开发纳米技术在小鼠和人类肺肿瘤中系统地递送 miR-34a 型号 · 鉴定并验证与人类肺癌相关的新型 miR-34a 靶基因麻省理工学院杰克斯实验室及周边地区的研究环境提供了无与伦比的科学讨论、合作和培训的机会目前，我指导一名本科生。这是一名学生和一名技术助理，他们直接与我一起进行与我的研究相关的实验。这是一次令人难以置信的经历，它将赋予我管理独立企业所需的许多技能。麻省理工学院、布罗德研究所和哈佛医学院的科学界提供了无数的机会。研讨会和讲习班将继续促进我的科学发展。我的近期目标是开发本申请中描述的研究平台并证明其揭示 miR-34a 和其他肿瘤的分子和细胞机制的潜力我打算启动一个独立的研究项目来利用这些。通过研究多种肿瘤模型中的肿瘤抑制 miRNA 来开发体内系统从长远来看，我是这样的。相信这些实验将为我的研究计划奠定坚实的基础我期待着教育和招募与我一样对癌症充满热情的学生和博士后。研究。