The role of human milk miRNA at the intersection between maternal health and child growth and immune development - PROJECT SUMMARY/ABSTRACT MicroRNA (miRNA) are short, non-coding RNA that act as post-transcriptional regulators of gene expression and have been implicated in many pathways in infant development. Milk is one of the richest sources of miRNA in the human body, yet we know very little about how the maternal environment impacts miRNA profiles, and how this influences infant development. The overall objectives of this project are to a) characterize variations in the human milk miRNA profile of mothers who are underweight or harbor a helminth infection, and b) examine the relationship between miRNA profile and both infant weight gain and immune system maturation. To test this hypothesis, we will leverage a well-characterized longitudinal study of 400 pregnant women and their infants residing in The Philippines. Hence, this proposal requires no additional subject recruitment or sample collection. In Aim 1 we will determine the human milk miRNA profile in states of maternal disease including a) underweight mothers, with the hypothesis that mothers who are underweight will have decreases in miRNA related to growth, and b) mothers infected with the helminth Schistosoma japonicum, with the hypothesis that immunomodulatory miRNA will be down regulated. In Aim 2 we will then examine the impact of human milk miRNA on infants, including a) impaired weight gain, with the hypothesis that mother’s milk with low levels of growth-related miRNA will be associated with infant wasting, and b) immune system maturity, with the hypothesis that infants receiving milk with higher levels of immunoregulatory miRNA will have a more mature immune system. The candidate is firmly committed to a career in investigating the impact of human milk composition on infant growth and immune development and is strongly supported in her career and research goals by her mentors and her division at the Warren Alpert Medical School of Brown University, where she is an Assistant Professor of Emergency Medicine. The current proposal includes a comprehensive career development plan including hands-on training, coursework, and structured mentorship, to 1) acquire the conceptual frameworks and specific knowledge to understand human milk science in relation to maternal and child health, 2) strengthen skills in clinical epidemiology and biostatistics, with a focus on analysis of genomic data in relation to health outcomes, 3) develop expertise in the conduct of miRNA science, and 4) further career development as an independent physician scientist in global maternal child health research. The candidate’s primary mentor, Dr. Jeffrey Bailey, and her co-mentors, Dr. Jennifer Friedman, Dr. Ann Moormann, Dr. Sarbattama Sen, and Dr. Zhijin Wu all are NIH-funded career scientists with extensive experience in mentorship of early stage investigators to research independence. Completion of this comprehensive training plan will provide the candidate with the skills and experience necessary to become a successful independent investigator specializing in the impact of human milk profiles in infant growth and immune development.
