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Role of LncRNAs in diabetic livers

LncRNA 在糖尿病肝脏中的作用

基本信息

批准号：
9211319
负责人：
AMY Y LEUNG
金额：
$ 15.36万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9211319
关键词：
Affect Affinity Animal Model Applications Grants Atherosclerosis Award Biological Biological Assay Cardiovascular Diseases Cell Line Cells Chromatin Chromatin Structure Clinical Code Complex Data Development Diabetes Mellitus Diabetic Nephropathy Diabetic mouse Diet Disease Educational process of instructing Educational workshop Enhancers Epidemic Funding Future Gene Expression Gene Targeting Genes Genetic Genetic Models Gluconeogenesis Glucose Goals Grant Healthcare Systems Hepatic Hepatocyte High Fat Diet Human Hyperglycemia Immunoprecipitation In Vitro Incidence Individual Insulin Insulin Resistance Insulin Signaling Pathway K-Series Research Career Programs Kidney Diseases Knowledge Laboratories Liver Medical Mentors Metabolism Methods Molecular Molecular Biology Mus Neuropathy Non-Insulin-Dependent Diabetes Mellitus Overnutrition Pathogenesis Pathway interactions Physiological Physiology Population Process Proteins RNA Regulation Regulator Genes Regulatory Element Reporter Research Research Activity Research Personnel Research Training Role Scientist Severities Small Interfering RNA Structure System Testing Training Training Activity Training Programs Transcript Untranslated RNA Writing base blood glucose regulation career career development chromatin protein diabetic differential expression effective therapy experience genome-wide glucose production hepatoma cell improved in vivo innovation insight insulin mediators insulin sensitivity insulin signaling knock-down mouse model new therapeutic target non-genetic novel novel strategies overexpression public health relevance sedentary lifestyle skills success therapeutic target transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) is already placing a major burden on the US healthcare system and projections indicate the problem will get worse. It is therefore of great importance to further our understanding of the molecular mechanisms that contribute to the onset and establishment of T2D and its complications. This application proposes research and training plans for Dr. Leung to become a leading independent investigator in the field of diabetes. While the applicant has had extensive training in molecular biology and simple model organisms, her development and future success as an investigator will require additional practical skills and knowledge regarding advanced mouse models, mouse physiology and metabolism. To attain the necessary skills and knowledge, she has assembled a strong mentoring team comprising of a group of expert senior investigators and proposed a detailed list of career development and training activities. The mentors: Drs. Natarajan, Tontonoz, Rossi, and Lusis, represent a diverse set of investigators with a track record of successful mentoring and diabetes related research. They will provide guidance and assistance with Dr. Leung's research and training in the development of Dr. Leung's academic career as she transitions to an independently funded investigator. Over the course of this award, she will also engage in additional training activities including structured postgraduate courses intended to increase knowledge and skills in mouse metabolism and physiology, grant-writing workshops, laboratory management workshops, and teaching. The research activities proposed in this application will investigate the role of long non-coding RNAs (lncRNAs) in the development of insulin resistance, dysregulation of gluconeogenesis, and ultimately, T2D. This project is based on extensive preliminary data demonstrating that specific lncRNAs are dysregulated in livers of insulin resistant mice. The overarching hypothesis of this application is that lncRNAs are involved in modulating key genes that regulate insulin signaling pathways and hepatic glucose production, and that dysregulation of these lncRNAs can contribute to the development of insulin resistance and dysregulation of hepatic glucose production. The Specific Aims are: 1) to identify lncRNAs that are dysregulated in livers of diabetic mice, including both genetic and non-genetic mouse models, 2) to determine the functional consequences of altered expression of lncRNAs in the livers of diabetic mice, and 3) to characterize the mechanism of action and regulation of candidate lncRNAs in livers under diabetic conditions. The results from the proposed studies will provide significant new insights into the molecular mechanisms that accompany the development of hepatic insulin resistance and T2D and will form the basis of future grant applications from the applicant. This project will furthermore provide Dr. Leung with the necessary experience for her development into an independent scientist.