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，是良性平滑肌肿瘤细胞外基质蛋白的去固化。 UL是全球一个主要的健康问题，因为它几乎影响在所有妇女中，有70-80％的非裔美国人和不成比例的非洲裔美国人，但仍然很少了解。长我们团队的术语目标是系统地发现调节关键分子事件的新型机制有助于平滑肌瘤。该R01应用的直接目标是测试改变的假设表观基因组信号定义了正常的肌层组织和平滑肌瘤，以及治疗治疗的人体组织。使用与生物信息学和其他分析集成的全基因组研究，我们将确定表观基因组学子宫纤维化中的特征是第一次。这项无偏见的研究将确定表观基因组分化正常组织和患病的组织的特征，可能允许发展接受（靶向表观基因组）用于平滑肌瘤拟议的工作在科学，翻译和临床上是显着且高度创新的因为它代表了平滑肌瘤中表观基因组的第一个系统探索。从中获得的结果该分析将用于生成新的假设，以更好地了解平滑肌瘤。