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Molecular and Genomic Mechanisms in the Biology of Pregnancy and Parturition

妊娠和分娩生物学中的分子和基因组机制

基本信息

批准号：
10063444
负责人：
Maria Florian-Rodriguez
金额：
$ 131.62万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
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：
2016-12-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063444
关键词：
Acetylation Advisory Committees Binding Sites Biochemical Biological Biological Assay Biology Birth Budgets Cell Differentiation process Cells Cervical Cervical Ripening Cervix Uteri ChIP-seq Collaborations Competence Consent Forms Data Analyses Databases Discipline of obstetrics Enhancers Epigenetic Process Epithelial Epithelial Cells Equipment and Supplies Estrogen Receptor alpha Estrogen Receptor beta Estrogen Receptors Estrogens Experimental Designs Female Gene Expression Gene Expression Regulation Genes Genetic Transcription Genome Genomic Library Genomic approach Genomics Goals Grant Gynecologic Surgical Procedures HAS2 gene Hormones Hospitals Human Human Resources Hyaluronan IACUC Immune Impairment Incidence Infection Inflammatory Infrastructure Institutional Review Boards Invaded Laboratories Length Liquid substance Maintenance Manuscripts Mediating Molecular Molecular Probes Myometrial Nuclear Pathway interactions Physiological Pregnancy Premature Birth Premature Labor Preparation Procedures Process Progesterone Progesterone Receptors Program Research Project Grants Protein Isoforms Proteins Receptor Activation Records Regulation Reporting Research Research Personnel Research Project Grants Role Schedule Services Signal Pathway Signal Transduction Site Stromal Cells Structure Techniques Technology Teleconferences Term Birth Testing Time Tissue Banks Tissue Sample Tissues Training Uterus archive data base biological systems chromatin modification clinically relevant computerized tools cost data archive epigenetic regulation epigenomics global run on sequencing human tissue in vivo inflammatory modulation meeting abstracts meetings microorganism myometrium next generation sequencing pregnant premature prevent progesterone receptor A progesterone receptor B programs receptor function reproductive reproductive tract tool transcription factor transcriptome sequencing

项目摘要

PROJECT SUMMARY/ABSTRACT In this new program project, we will utilize comprehensive global genomic approaches (RNA sequencing [RNA-seq], global run-on sequencing [GRO-seq], and chromatin immunoprecipitation sequencing [ChIP-seq]) to understand the biological mechanisms for term and preterm birth. This application is timely, because of the huge advances in genomic technologies combined with cutting-edge computational tools, which have dramatically advanced our understanding of signal-regulated gene transcription in a wide variety of biological systems. The global views generated by these assays provide a uniquely informative biological perspective that cannot be achieved by analyzing one or even a few genes at a time. We propose to utilize these state-of-the-art techniques to develop an in-depth understanding of the genomic and epigenomic mechanisms that underlie the regulation of myometrial quiescence-contractility, cervical competency-dilation, and that maintain barrier function of the cervix to protect the pregnancy against invading microorganisms and prevent prematurity. The P01 includes four interrelated projects: Project 1: Epigenetic Regulation of Myometrial Contractility in Pregnancy and Labor (Carole R. Mendelson); Project 2: Functional Roles of Estrogen Receptor α Acetylation in the Uterus (W. Lee Kraus); Project 3: Genomic Consequences of Estrogen Receptor Activation in the Cervix (R. Ann Word); Project 4: Mechanisms of Cervical Epithelial Barrier Protection Against Ascending Infection and Preterm Birth (Mala S. Mahendroo), supported by three cores: Administrative Core (Mendelson); Genomics and Computational Core (Kraus); Human Tissue and Biological Fluid Acquisition Laboratory Core (Word). The goals of these projects are: Project 1 - to define the genes and mechanisms that underlie the actions of progesterone (P4), via progesterone receptor isoforms, PR-A and PR-B, on inflammatory and `contractile' gene expression, and to characterize the chromatin modifications that mediate myometrial quiescence and accompany enhanced contractile gene expression leading to term and preterm labor; Project 2 - to achieve a better understanding of the biology of estrogen signaling through estrogen receptor α (ERα) in the female reproductive tract during pregnancy and parturition by elucidating the role of ERα acetylation in the function of the uterus and cervix of pregnant females and the molecular mechanisms by which ERα acetylation controls ERα-dependent gene regulation in these tissues; Project 3 - to understand the mechanisms by which PRs and ERs interact to alter gene expression, gestational length, and structural integrity of the cervix during pregnancy, cervical ripening and parturition, and; Project 4 – to utilize genomic, cell biological and biochemical approaches to advance our understanding of the mechanisms by which hyaluronan (HA) provides immune- protection and epithelial barrier function in the pregnant cervix, as well as the molecular mechanisms whereby HA synthase 2 is regulated. We propose that these interrelated projects, carried out by a highly interactive research team, will achieve our long-range goal of reducing the incidence of preterm birth.

项目总结/摘要在这个新的计划项目中，我们将利用全面的全球基因组方法（RNA测序[RNA-seq]，全球运行测序[GRO-seq]和染色质免疫沉淀测序[ChIP-seq]），了解足月和早产的生物学机制。这个应用程序是及时的，因为基因组技术的巨大进步与尖端的计算工具相结合，极大地促进了我们对各种生物系统中信号调节基因转录的理解。这些检测产生的全局视图提供了一个独特的信息丰富的生物学视角，通过一次分析一个甚至几个基因来实现。我们建议利用这些最先进的技术，以深入了解基因组和表观基因组机制，调节子宫肌层静止-收缩、宫颈功能-扩张和维持屏障子宫颈的功能，以保护怀孕免受微生物入侵，防止早产。的 P01包括四个相互关联的项目：项目1：怀孕和分娩（Carole R。项目2：雌激素受体α乙酰化的功能作用在子宫（W. Lee Kraus）;项目3：子宫颈中雌激素受体激活的基因组后果（R. Ann Word）;项目4：宫颈上皮屏障对上行感染的保护机制，早产（Mala S. Mahendroo），由三个核心支持：行政核心（Mendelson）;基因组学和计算核心（克劳斯）;人体组织和生物流体采集实验室核心（Word）。的这些项目的目标是：项目1 -确定基因和机制，这些行动的基础孕酮（P4），通过孕酮受体亚型，PR-A和PR-B，对炎症和“收缩”基因表达，并表征介导子宫肌层静止的染色质修饰，伴随着增强的收缩基因表达，导致足月和早产;项目2 -实现一个更好地了解女性通过雌激素受体α（ERα）的雌激素信号传导的生物学通过阐明ERα乙酰化在妊娠和分娩过程中生殖道功能中的作用，妊娠女性的子宫和宫颈以及ERα乙酰化控制的分子机制这些组织中的ERα依赖性基因调控;项目3 -了解PR和ER α依赖性基因调控的机制。 ER相互作用，改变基因表达，妊娠期长度和子宫颈的结构完整性，妊娠、宫颈成熟和分娩;项目4 -利用基因组、细胞生物学和生物化学方法，以促进我们的机制，透明质酸（HA）提供免疫- 保护和上皮屏障功能，以及分子机制， HA合成酶2受到调节。我们建议，这些相互关联的项目，由一个高度互动的研究团队的努力，将实现我们降低早产发生率的长期目标。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Collagen Type 1 Accelerates Healing of Ruptured Fetal Membranes.

胶原蛋白 1 型可加速胎膜破裂的愈合

DOI：
10.1038/s41598-017-18787-9
发表时间：
2018-01-12
期刊：
Scientific reports
影响因子：
4.6
作者：
Mogami H;Kishore AH;Word RA
通讯作者：
Word RA

Protocol to dissociate epithelia from non-pregnant and pregnant mouse cervical tissue for single-cell RNA-sequencing.

DOI：
10.1016/j.xpro.2023.102631
发表时间：
2023-12-15
期刊：
STAR PROTOCOLS
影响因子：
0
作者：
Madhukaran, Shanmugapriyaa;Hon, Gary C.;Mahendroo, Mala
通讯作者：
Mahendroo, Mala

Dysregulation of fibulin-5 and matrix metalloproteases in epithelial ovarian cancer.

DOI：
10.18632/oncotarget.24484
发表时间：
2018-03-06
期刊：
Oncotarget
影响因子：
0
作者：
Manders DB;Kishore HA;Gazdar AF;Keller PW;Tsunezumi J;Yanagisawa H;Lea J;Word RA
通讯作者：
Word RA

Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity.