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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：
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
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/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

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.

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