Integrative Longitudinal Genomics of Maternal Asthma-Preeclampsia Overlap and Risk of Childhood Asthma

母亲哮喘-先兆子痫重叠和儿童哮喘风险的综合纵向基因组学

• 批准号: 10079504
• 负责人: Hooman Mirzakhani
• 金额: $ 17.5万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-03 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10079504
• 关键词: 25-hydroxyvitamin D; Academic Medical Centers; Achievement; Address; Affect; Age; Asthma; Biological; Biological Markers; Biometry; Blood; Blood specimen; Body mass index; Child; Childhood Asthma; Clinical; Clinical Research; Code; Comparative Genomic Analysis; Complex; Data; Development; Disease; Doctor of Philosophy; Early Diagnosis; Epidemiology; Essential Genes; Future; Gene Expression; Genes; Genomics; Goals; Grant; Health; High-Throughput Nucleotide Sequencing; Hospitals; Inflammation; Investigation; Late pregnancy; Lead; Life; Maternal-Fetal Exchange; Maternal-fetal medicine; Measurement; Measures; Medical; Medicine; Mentors; Messenger RNA; MicroRNAs; Molecular; Morbidity - disease rate; Mothers; Multiomic Data; Neonatal Mortality; Netherlands; Pathway interactions; Pharmacogenetics; Pharmacogenomics; Phase; Physiological; Placenta; Pre-Eclampsia; Pregnancy; Pregnant Women; Prevalence; Prevention; Preventive; RNA; Records; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Science; Scientist; Systems Biology; Time; Tissues; Training; Translational Research; Translations; Umbilical Cord Blood; Validation; Vitamin D; Wheezing; Woman; antenatal; asthmatic; base; biomedical informatics; career; circulating microRNA; clinical practice; cohort; developmental plasticity; differential expression; early childhood; early detection biomarkers; early pregnancy; fetal; gene environment interaction; genetic signature; genomic data; genomic signature; high risk; immunoregulation; in utero; insight; instructor; interest; maternal condition; medical schools; miRNA expression profiling; mortality; multidisciplinary; neonatal morbidity; neonate; next generation sequencing; novel; offspring; pathophysiology of preeclampsia; peripheral blood; pre-clinical; preclinical development; pregnancy disorder; prenatal; prenatal risk factor; preservation; protein protein interaction; respiratory; transcriptome; transcriptomics

Abstract- The goal of this project is to use a systematic and integrative computational approach in genomic analysis to find novel genes, biological networks and pathways overlapping preeclampsia (PE) and prenatal maternal asthma as a risk factor for both PE and childhood asthma. In this approach, we will integrate two types of genomics data derived from Next-Generation Sequencing (mRNA-miRNA seq), to discover new biological pathways conferring risk of childhood asthma. Specific aims rely on longitudinal high throughput sequencing of maternal peripheral blood RNA at 10-18 and 32-38 weeks of pregnancies with asthma and PE and cord blood at delivery in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). We will replicate the disease module and biological candidates in a second cohort of pregnancies (LifeCodes). Successful achievement of the objective of this project will help to identify biomarkers for early diagnosis of PE, and genomic factors contributing to both PE and maternal asthma during pregnancy as well as a future plan for translation of these discoveries into clinical practice for prevention of PE and childhood asthma. The project will be led by Hooman Mirzakhani, MD, PhD, MMSc who is an Instructor in Medicine at Channing Division of Network Medicine Division (CDNM) at Brigham and Women’s Hospital (BWH). During his training, he has received a Master of Medical Science degree in Biomedical Informatics from Harvard Medical School and a Doctor of Philosophy in Pharmacogenetics and Pharmacogenomics from Leiden University Medical Center, The Netherlands. At the CDNM, he has been pursing epidemiologic and genomic investigations into the early origins of PE, asthma during pregnancy, role of vitamin D in asthma and PE with a particular interest in secondary influences of asthma and vitamin D on PE development and risk of childhood asthma. Dr. Mirzakhani plans to develop his career in the academic field of translational biomedical science. Successful completion of this proposal will result in advanced training in systems biology required for a future independent career as a scientist to elucidate the early origins of childhood asthma and its prenatal risk factors including hypertensive disorders of pregnancy that cause maternal-fetal morbidity and affect mother and neonates’ long-term health. Dr. Mirzakhani will use samples from the VDAART study for the discovery phase and additional subjects’ samples for replication will be provided by Dr. McElrath, PI of the LifeCodes cohort at Division of Maternal-Fetal Medicine at BWH. He will be mentored and advised by Scott T. Weiss, MD, MS, and Joseph Loscalzo, MD, PhD, MA, Thomas F. McElrath, MD, PhD, Albert-Laszlo Barabasi, PhD, and Vincent J. Carey, PhD, a multidisciplinary team of experts and leaders in clinical, biomedical, biostatistical and translational research with excellent track records of mentoring young investigators towards independent research careers.

抽象的- 该项目的目的是在基因组分析中使用系统和集成的计算方法 要找到新的基因，生物网络和途径重叠的先兆子痫（PE）和产前重叠 母体哮喘是PE和儿童哮喘的危险因素。在这种方法中，我们将整合两个 从下一代测序（mRNA-MIRNA SEQ）得出的基因组学数据类型，以发现新的 生物途径会议会议的童年哮喘风险。具体目标依赖纵向高通量 在10-18和32-38周的哮喘和哮喘和32-38周的主要外周血RNA测序 在维生素D产前减少哮喘试验（VDAART）中，PE和脐带血分娩时。我们将 复制第二个妊娠（生命周期）中的疾病模块和生物候选物。 成功实现该项目的目标将有助于确定生物标志物的早期诊断 PE和基因组因素在怀孕期间以及未来都导致PE和母体哮喘 计划将这些发现翻译成预防PE和儿童哮喘的临床实践。 该项目将由医学博士Hooman Mirzakhani领导，MMSC，他是医学的教练 Brigham和妇女医院（BWH）网络医学部（CDNM）的Channing部门。期间 他的培训，他获得了哈佛大学的生物医学信息学硕士学位 医学院和莱顿的药物遗传学和药物基因组学哲学博士 荷兰大学医学中心。在CDNM，他一直在追求流行病学和 对PE的早期起源，妊娠期间哮喘，维生素D在哮喘中的作用的基因组研究 PE对哮喘和维生素D对PE发育的次要影响特别感兴趣 儿童哮喘的风险。 Mirzakhani博士计划在翻译学术领域发展自己的职业 生物医学科学。该提案的成功完成将导致系统生物学的高级培训 作为科学家将来独立职业所必需的，以阐明儿童哮喘的早期起源和 其产前危险因素，包括引起母亲发病率的高血压疾病 并影响母亲和新生儿的长期健康。 Mirzakhani博士将使用Vdaart的样品 研究阶段的研究和其他主题的复制样本将由博士提供。 McElrath，BWH的孕产妇医学司的生命系数队列的PI。他会被考虑 并由医学博士Scott T. Weiss和医学博士Joseph Loscalzo，MA，MA，Thomas F. McElrath，MD， 博士，Albert-Laszlo Barabasi博士和博士和Vincent J. Carey，Phd，多学科专家团队， 临床，生物医学，生物统计学和翻译研究的领导者，具有出色的记录 指导年轻的研究人员致力于独立的研究职业。