The Epitranscriptome as a Novel Mechanism of Arsenic-Induced Diabetes.

表观转录组作为砷诱发糖尿病的新机制。

• 批准号: 10747037
• 负责人: Andrea Baccarelli
• 金额: $ 6.9万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10747037
• 关键词: Address; Adult; Air; American Indians; Arsenic; Biological; Biological Markers; Blood; Cardiometabolic Disease; Career Transition Award; Cell Communication; Cells; Chronic; Clinical; Communication; Communities; Complications of Diabetes Mellitus; Coupled; Data; Diabetes Mellitus; Diagnosis; Disease; Early Diagnosis; Enrollment; Environmental Health; Environmental Risk Factor; Epidemiology; Epigenetic Process; Equation; Exposure to; Faculty; Family Study; Food; Foundations; Funding; Genes; Genetic Transcription; Geography; Glucose Intolerance; Goals; Grant; Health; Health Sciences; Heart; High Prevalence; Human; Hyperglycemia; Indigenous; Insulin Resistance; Intervention; Knowledge; Laboratories; Linear Regressions; Link; Measurement; Mediating; Mentors; Mentorship; Messenger RNA; Metabolic; Metabolic syndrome; Metabolism; MicroRNAs; Modality; Modeling; Modification; Molecular; Molecular Epidemiology; Native Hawaiian; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Outcome; Parents; Participant; Pathogenesis; Pathway interactions; Persons; Phenotype; Physiological; Plasma; Population; Population Research; Postdoctoral Fellow; Prevention; Prognosis; Public Health; RNA; Research; Research Personnel; Research Project Grants; Risk; Role; Safety; Sampling; Small RNA; Soil; Source; Spottings; Structure; Technology; Toxic Environmental Substances; Training; Universities; Untranslated RNA; Urine; Water; Writing; cardiometabolism; career; career development; cohort; drinking water; epitranscriptome; epitranscriptomics; experience; extracellular vesicles; fasting glucose; genetic regulatory protein; ground water; high risk; insight; intercellular communication; member; multidimensional data; next generation; novel; public drinking; research and development; skill acquisition; skills; sociodemographics; targeted sequencing; targeted treatment; training opportunity; transcriptome sequencing

Project Summary The primary goal of this research project is to investigate extracellular vesicle-derived microRNAs (EV- miRNAs) as a potential mechanistic biomarker of arsenic (As)-associated type 2 diabetes mellitus (T2DM), and its related conditions, in American Indians (AIs). The proposed research is a supplement to an ongoing R01 that is investigating the epitranscriptomic RNA modification N6-methyladenosine as a mechanism of As- induced T2DM from AIs participating in the same cohort. The candidate for the diversity supplement is a second year postdoctoral researcher in the Department of Environmental Health Sciences at Columbia University in the Laboratory of Precision Environmental Health. The candidate is of Native Hawaiian descent, and is to our knowledge, the only Native Hawaiian at the postdoctoral level at Columbia University. Throughout the proposed research and career development training, he will have a strong mentorship team composed of co-mentors Dr. Navas-Acien, PI of the parent R01, and Dr. Baccarelli, co-PI of the parent R01, with additional support from a junior faculty member leading the research team of the parent R01, Dr. Kupsco. The candidate is responsible for the completion of the proposed aims of the research project, including 1) characterizing circulating EV-miRNAs that are associated with As exposure and As metabolism using next-generation RNA sequencing targeted to small RNAs in AIs enrolled in the Strong Heart Study (SHS); 2) identify EV-miRNAs that associate with T2DM risk, including insulin resistance, hyperglycemia, and metabolic syndrome, as well as incident/prevalent T2DM; 3) investigate whether EV-miRNAs mediate the relationship between As and As metabolism, and T2DM-related outcomes; and 4) identify biological pathways linking EV-miRNA signatures of As-associated T2DM with changes in epitranscriptomic signatures. Throughout the proposed research, the candidate will have a structured training plan that will facilitate the acquisition of skillsets necessary for his short-term goal of acquiring a K99/R00 career transition award and his long-term career goal as an independent academic researcher, this experience and training include, 1) advanced computational approaches for population-based research, high-dimensional data, and molecular epidemiology; 2) community- based and Indigenous health research approaches for cardiometabolic diseases; 3) grant writing for federal funding; 4) authoring and communicating Indigenous Health Research; and 5) navigating a career in academic research. To facilitate these training goals, the candidate will be involved in several formal training opportunities offered through Columbia University, he will garner experience through involvement on the parent R01, and he will meet weekly with members of his mentorship team.

项目摘要 该研究项目的主要目的是研究细胞外囊泡衍生的microRNA（ev- miRNA）作为砷（AS）相关2型糖尿病（T2DM）的潜在机械生物标志物，并且 它的相关条件，美国印第安人（AIS）。拟议的研究是对正在进行的R01的补充 这是在研究表面参考的RNA修饰N6-甲基二糖苷作为AS-的机制 来自AIS参与同一队列的诱导T2DM。多样性补充的候选人是 哥伦比亚环境卫生科学系的第二年博士后研究员 精确环境健康实验室的大学。候选人是夏威夷本地人的血统， 据我们所知，这是哥伦比亚大学博士后唯一的夏威夷人。自始至终 拟议的研究和职业发展培训，他将拥有一个由强大的指导团队组成 父母R01的PI Navas-Acien博士和父母R01的Co-Pi的Baccarelli博士，还有其他 初级教师领导家长R01研究小组Kupsco博士的支持。候选人 负责完成研究项目的拟议目标，包括1）表征 循环EV-MIRNA与接触和使用下一代RNA相关的代谢相关 在进行强大心脏研究（SHS）的AIS中针对小型RNA的测序； 2）识别EV-MIRNA 与T2DM风险相关的，包括胰岛素抵抗，高血糖和代谢综合征，以及 事件/流行的T2DM; 3）研究EV-MIRNA是否介导AS和AS之间的关系 代谢和与T2DM相关的结果； 4）确定连接EV-MIRNA特征的生物学途径 随着表面转录组特征的变化而相关的T2DM。在整个拟议的研究中， 候选人将制定一个结构化的培训计划，以促进他的技能的获取 获得K99/R00职业过渡奖的短期目标以及他作为一个长期职业目标 独立的学术研究员，这种经验和培训包括，1）高级计算 基于人群的研究，高维数据和分子流行病学的方法； 2）社区 - 基于心脏代谢疾病的基于原住民健康研究方法； 3）联邦的赠款 资金; 4）创作和交流土著健康研究； 5）从事学术职业 研究。为了促进这些培训目标，候选人将参与几项正式培训 通过哥伦比亚大学提供的机会，他将通过参与父母获得经验 R01，他将每周与他的指导团队成员见面。