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