Placental and breastmilk microRNAs in relation to early-life growth and metabolism

Project Summary The work outlined in this proposal is meant to provide the training and skills necessary to begin my independent academic career as a molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. My doctoral research focused on the mechanistic relationship of DNA methylation and gene transcription, which paved the way for the analysis and interpretation of more complicated population studies of the molecular mechanisms that underlie gestational exposures. My experience has led to my primary research interest in how early-life exposures influence children's health. I will accomplish my goals through training, mentorship and a rigorous research project that integrates genetic, epigenetic and transcriptomic measures to assess the role of placenta- and breastmilk-mediated exposures in relation to early-life growth and metabolism. Through my research and training plan, I will gain expertise in epidemiologic methods and study design; childhood growth, nutrition and obesity; and microRNA biology. I will receive personalized training from my co-mentors, Dr. Carmen Marsit, an expert in molecular epidemiology, and Dr. Usha Ramakrishnan, an expert in children's growth and nutrition. I will receive additional guidance from a transdisciplinary advisory committee composed of Drs. Margaret Karagas, Michael Epstein, and Scott Langevin. This team has expertise in integrative genomics, bioinformatics, statistical genetics, early-life epidemiology and microRNA biology. Emory University is home to Rollins School of Public Health, ranked 5th in the US, as well as to world leaders in epidemiology and human genetics research. The formal training and expert guidance I will receive here will enable me to achieve my long-term career goal of becoming an independent, early-life molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. The research proposed here will address the following gaps in knowledge: 1) the role of placental microRNAs in early-childhood growth and metabolism; 2) the genetic and epigenetic dynamics that underlie microRNA expression in placenta; and 3) the role of placental and extracellular breastmilk microRNAs as mediators of maternal metabolic status influence on early childhood metabolic status. My research will provide insight into the contribution of gestational and early-life exposures in the development of early growth and metabolic status. More broadly, the knowledge gained through this research study has the potential to contribute to microRNA biology, placental biology, obesity and to the Developmental Origins of Health and Disease (DOHaD). Finally, my proposed training and research will prepare me for an independent research career, in which I utilize cutting-edge `omics methods in population-studies to assess the molecular mechanisms that underlie children's health and develop biomarkers that inform recommendations for disease prevention.