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

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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.