Network-based analysis of disease-associated epigenetic changes in youth electronic cigarette users

基于网络的青少年电子烟使用者疾病相关表观遗传变化分析

• 批准号: 10680306
• 负责人: AHMAD BESARATINIA
• 金额: $ 24.84万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680306
• 关键词: Address; Algorithms; Area; Biochemical; Biological; Biological Markers; Biological Specimen Banks; California; Carcinogens; Cells; Characteristics; Collaborations; Collection; Computer Models; Data; Data Set; Development; Devices; Diet; Disease; Dose; Electronic cigarette; Epidemic; Epigenetic Process; Funding; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Generations; Genes; Genetic Transcription; Health; Laboratories; Leukocytes; Life Style; Link; Marketing; Measurement; Measures; Mediating; Methods; Modeling; Molecular; National Institute of Dental and Craniofacial Research; Network-based; Nicotine; Oral; Pathway Analysis; Population; Process; Public Health; Regulation; Regulator Genes; Risk; Risk Assessment; Sampling; Smoking Status; Source; Special Population; Specimen; Study Subject; Systems Biology; Tissue-Specific Gene Expression; Tissues; Untranslated RNA; Vulnerable Populations; Walking; Youth; demographics; disorder risk; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; health assessment; innovation; interest; manufacture; novel marker; peripheral blood; preservation; public health relevance; public repository; recruit; tobacco products; tobacco regulation; toxicant; transcriptome sequencing; vaper; vaping

The widespread use of electronic cigarettes (e-cigs) by youth is a significant public health problem in the US and many parts of the world. To date, the long-term health effects of e-cig use in this vulnerable population are largely unknown. Many toxicants and carcinogens present in e-cig vapor exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) are key epigenetic regulators of gene expression in health and disease states. Approach: To investigate lncRNA-mediated gene regulation and its association with disease development in youth vapers, we will perform RNA-seq and network-based analyses on cells and tissues of youth e-cig users as compared to non-users. Aim 1a: Using a systems biology approach, we will detect aberrant lncRNAs and their interaction networks that drive gene dysregulation in youth e-cig users. The detected lncRNAs that govern gene dysregulation in youth e-cig users can serve as novel biomarkers of exposure and effects for vaping. Aim 1b: Applying advanced prediction methods, we will identify which diseases are associated with the aberrant lncRNAs detected in youth e-cig users. Aberrant lncRNAs in youth e-cig users that are associated with specific diseases can be used for risk assessment of vaping. Aim 2: Using computational modeling, we will find the associations between aberrant lncRNAs and the intensity and duration of vaping (i.e., dose) and the characteristics of vaping products used by youth. Identifying product characteristics that influence the lncRNA- mediated gene dysregulation in youth e-cig users can inform the FDA’s regulation of tobacco products to protect youth and promote public health. Responsiveness to RFA-OD-21-004: This proposal will maximize the use of existing biospecimens from our recently completed NIDCR-funded project whose study subjects were recruited through collaboration with USC- TCORS, which is sponsored by the FDA|CTP. This is a unique collection of biospecimens from a representative sample of population in Southern California. No publicly available repository in the US offers similar specimens needed for this proposal. We will generate scientific evidence on the health risks of e-cig use in youth, thus informing the FDA’s regulation of tobacco products to protect this vulnerable population and promote public health. We will use an innovative approach to address two scientific interest areas in this RFA, including assessment of (1) exposure; and (2) potential harm from vaping in youth, who are a population of special relevance. By elucidating the molecular changes that underlie the biological consequences of e-cig use in youth, we will develop novel biomarkers of exposure and effects. These biomarkers will have significant utility for assessing the health risks of e-cig use in this vulnerable population. By determining how vaping dose and product characteristics can modulate the induced biological effects in youth e-cig users, we will provide urgently needed data to inform the FDA’s regulation of tobacco products to protect youth and promote public health.

在美国和英国，青少年广泛使用电子烟（e-cigs）是一个重大的公共卫生问题