Microbial translocation, inflammation, and adverse pregnancy outcomes in humans

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 DESCRIPTION (provided by applicant): There are two primary goals of this K24 proposal. The first is to provide time for the candidate, Jennifer Friedman, MD, PhD, to provide mentorship to junior faculty in patient oriented research (POR) addressing mechanisms of morbidity related to parasitic diseases among pregnant women and children. The second goal is to provide time for Dr. Friedman to further her own career development by allowing her to pursue advanced coursework related to her career goals. Brown University affiliated hospitals provide a rich source of potential mentees from a range of Departments/Divisions housing junior faculty interested in conducting POR in global health. The Departments and Institution provide significant direct support for junior faculty conducting POR. addition, although there are numerous other training grants, there are three T32 awards, two Centers for Biomedical Research Excellence (COBRE) awards, and one T37, which could specifically provide funding for junior faculty conducting POR in research areas of interest to Dr. Friedman e.g., neglected tropical diseases, infectious disease pathogenesis, and perinatal biology. The overarching scientific goal of this proposal is to advance studies elucidating mechanisms through which immune responses at the maternal-fetal interface culminate poor growth in utero, prematurity, and newborn iron insufficiency. Mentees will be able to leverage well-characterized samples and outcomes from a large scale, NIH funded randomized controlled trial of Praziquantel given at 12 - 16 weeks gestation in Leyte, The Philippines. The trial ended in December of 2012 and all samples are available for immediate use. We will specifically examine the role of both parasitic antigens and microbial translocation, the process of microbial products from the gut entering the systemic circulation, with consequent inflammation in the pathogenesis of IUGR, prematurity, and newborn iron insufficiency. No studies have evaluated microbial translocation (MT) in the context of human diseases of pregnancy. Specifically, we will use this model to identify pathways through which MT and inflammation in these compartments affect placental and newborn IGF pathways and iron transfer and how this ultimately influences fetal growth and iron endowment Though these scientific aims are provided in great detail to provide an example of the candidate's areas of interest and expertise, mentees will also be involved with direct subject enrollment, assessments, and long term follow up in The Philippines as part of 1) our Tropical Medicine and Research Centers grant with The Philippines, 2) our R01 (PI Kurtis, Co-I Friedman) that will enroll and follow subjects in 2015-16, or 3) as part of their own projects in POR in global health as supported by the aforementioned training grants and conducted at a well-funded site in Leyte, The Philippines, where the PI has had a longstanding and fruitful collaborations. She will therefore be able to model this collaborative approach.