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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

基本信息

批准号：
10326827
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
项目类别：
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/10326827
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 Hypertension 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

项目摘要

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.

摘要-- 本项目的目标是在基因组分析中使用系统的和综合的计算方法寻找新的基因，生物网络和途径重叠先兆子痫（PE）和产前母亲哮喘是PE和儿童哮喘的危险因素。在这种方法中，我们将整合两个来自下一代测序（mRNA-miRNA seq）的基因组学数据类型，以发现新的导致儿童哮喘风险的生物学途径。具体目标依赖于纵向高吞吐量对妊娠10-18周和32-38周哮喘患者的母体外周血RNA进行测序，维生素D孕妇哮喘减轻试验（VDAART）中分娩时的PE和脐带血。我们将在第二组妊娠中复制疾病模块和生物候选物（LifeCodes）。本项目目标的成功实现将有助于确定生物标志物，用于早期诊断 PE，以及导致妊娠期PE和母体哮喘的基因组因素以及未来计划将这些发现转化为预防PE和儿童哮喘的临床实践。该项目将由Hooman Mirzakhani，MD，PhD，MMSC领导，他是一名医学讲师，布里格姆妇女医院（BWH）网络医学部（CDNM）的钱宁部。期间在他的训练中，他获得了哈佛生物医学信息学医学科学硕士学位莱顿医学院，药物遗传学和药物基因组学博士荷兰大学医学中心。在CDNM，他一直在追求流行病学和 PE早期起源的基因组研究，妊娠期哮喘，维生素D在哮喘中的作用和PE，特别关注哮喘和维生素D对PE发展的继发性影响，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涯，生物医学科学成功完成本提案将导致系统生物学的高级培训作为一名科学家，阐明儿童哮喘的早期起源，其产前危险因素包括导致母儿发病的妊娠期高血压疾病并影响母亲和新生儿的长期健康。米尔扎哈尼博士将使用VDAART的样本发现阶段的研究和用于复制的额外受试者样本将由Dr. McElrath，BWH母胎医学部LifeCodes队列的PI。他会得到指导由Scott T.韦斯，医学博士，理学硕士，和约瑟夫Loscalzo，医学博士，哲学博士，硕士，托马斯F。McElrath，医学博士，博士，Albert-Laszlo Barabasi博士和Vincent J. Carey博士，一个多学科专家团队，临床、生物医学、生物统计学和转化研究领域的领导者，指导年轻的研究人员走向独立的研究生涯。