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Integrative Genomics, Epigenomics and Bioinformatics Analyses of Human Uterine Fibroids

人类子宫肌瘤的综合基因组学、表观基因组学和生物信息学分析

基本信息

批准号：
9975635
负责人：
Grant D Barish
金额：
$ 67.11万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-16 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975635
关键词：
3-Dimensional Affect African American Architecture Benign Bioinformatics Biological Biological Assay ChIP-seq Chromatin Chromatin Loop Complex Cytoskeleton DNA DNA Methylation Data Deoxyribonucleases Deposition Development Disease Enhancers Epigenetic Process Estrogens Event Extracellular Matrix Extracellular Matrix Proteins Family Fibroid Tumor Fibrosis Future Gene Expression Regulation Genes Genetic Genetic Transcription Genomics Goals Gonadotropin-Releasing Hormone Analog Health Health Care Costs Hemorrhage High Prevalence Histones Human Hypersensitivity Hysterectomy Infertility Knowledge Lead Leiomyoma Maps Medical Molecular Morbidity - disease rate Myometrial Nuclear Receptors Nucleic Acid Regulatory Sequences Pelvic Pain Play Progesterone Proteins RNA Polymerase II Recurrence Resolution Role Sampling Signal Pathway Signal Transduction Site Smooth Muscle Myocytes Smooth Muscle Tumor Testing Therapeutic Therapeutic Intervention Time Tissues Transforming Growth Factor beta Uterine Fibroids Uterus Woman Work base bisulfite sequencing cell type clinically significant epigenome epigenomics genome-wide genome-wide analysis hormone therapy human disease human tissue innovation malignant breast neoplasm methylation pattern myometrium new therapeutic target novel pre-clinical promoter reproductive response side effect steroid hormone transcription factor treatment response tumor tumorigenesis whole genome

项目摘要

Uterine leiomyomas (UL), also known as uterine fibroids, are benign smooth muscle tumors with excessive depostition of extracellular matrix proteins. UL is a major health problem worldwide, because it affects almost 70-80% of all women and disproportionally African Americans, but still remains poorly understood. The long term goal of our team is to systematically discover novel mechanisms regulating key molecular events that contribute to leiomyoma. The immediate goal of this R01 application is to test the hypothesis that altered epigenomic signatures define normal myometrial tissues and leiomyomas, and therapy treated human tissues. Using genome-wide studies integrated with bioinformatic and other analyses, we will determine the epigenomic signatures in uterine fibrosis for the first time. This unbiased study will identify epigenomic differentiating features of normal and diseased tissues and may allow for development of Epitherapy (targeting the epigenome) for leiomyomas The proposed work is scientifically, translationally, and clinically significant and highly innovative because it represents the first systematic exploration of the epigenome in leiomyomas. Results obtained from this analysis will be used to generate new hypotheses to better understand the molecular underpinning of leiomyomas.

子宫平滑肌瘤（UL），也称为子宫肌瘤，是一种良性平滑肌肿瘤，细胞外基质蛋白沉积。UL是全球范围内的一个主要健康问题，因为它几乎影响 70-80%的女性和非裔美国人，但仍然知之甚少。长我们团队的长期目标是系统地发现调节关键分子事件的新机制，有助于平滑肌瘤。此R 01应用程序的直接目标是测试改变了表观基因组标记定义了正常子宫肌层组织和平滑肌瘤以及治疗处理的人类组织。使用全基因组研究与生物信息学和其他分析相结合，我们将确定表观基因组子宫纤维化的特征。这项无偏倚的研究将确定表观基因组分化特征的正常和患病组织，并可能允许发展Epitherapy（针对表观基因组）用于平滑肌瘤所提出的工作具有科学性、实用性和临床意义，具有很强的创新性因为它代表了对平滑肌瘤表观基因组的首次系统性探索。所得结果这一分析将用于产生新的假设，以更好地理解平滑肌瘤