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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：
8916640
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/8916640
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.

项目总结/文摘