Microbial translocation, inflammation, and adverse pregnancy outcomes in humans

人类微生物易位、炎症和不良妊娠结局

• 批准号: 9207123
• 负责人: JENNIFER F FRIEDMAN
• 金额: $ 15.83万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9207123
• 关键词: Address; Affect; Age; Albumins; Anemia; Antigens; Apoptosis; Area; Award; Binding; Biological Assay; Biology; Birth; Birth Weight; Blood; Blood Circulation; Cachexia; Carrier Proteins; Centers of Research Excellence; Child; Childhood; Collaborations; Communicable Diseases; Data; Detection; Disease; Doctor of Philosophy; Endotoxins; Endowment; Enrollment; Faculty; Fetal Growth; Fetal Growth Retardation; Formalin; Funding; Goals; Grant; Growth; Health; Hospitals; Housing; Human; IL8 gene; Immune response; Immunologist; Individual; Infection; Inflammation; Inflammatory; Institution; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Insulin-Like-Growth Factor I Receptor; Interdisciplinary Study; Interferon Type II; Interleukin-1 beta; Interleukin-6; Iron; Letters; Low Birth Weight Infant; Maternal-Fetal Exchange; Measures; Mediating; Mentors; Mentorship; Messenger RNA; Methods; Modeling; Morbidity - disease rate; Newborn Infant; Outcome; Parasitic Diseases; Pathogenesis; Pathway Analysis; Pathway interactions; Perinatal; Philippines; Physicians; Placebos; Placenta; Praziquantel; Pregnancy; Pregnant Women; Process; Proteins; Publications; Publishing; Randomized; Randomized Controlled Trials; Regulation; Research; Research Support; Risk; Role; Sampling; Schistosoma; Schistosoma japonicum; Schistosomiasis; Scientist; Serum; Site; Source; Stream; Syncytiotrophoblast; TNF gene; TdT-Mediated dUTP Nick End Labeling Assay; Techniques; Time; Tissues; Training; Tropical Medicine; Umbilical Cord Blood; United States National Institutes of Health; Universities; Western Blotting; Woman; Work; adverse outcome; adverse pregnancy outcome; career; career development; collaborative approach; egg; fetal; follow-up; global health; hepcidin; hormone regulation; human disease; immunogenic; in utero; inflammatory marker; inflammatory milieu; interdisciplinary approach; interest; low and middle-income countries; metal transporting protein 1; microbial; neglected tropical diseases; neonatal death; novel; patient oriented research; premature; preterm newborn; protein transport; public health relevance; reproductive; skills; treatment effect; uptake

 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.

 描述（由适用提供）：该K24提案有两个主要目标。首先是为候选人詹妮弗·弗里德曼（Jennifer Friedman，MD）博士提供时间，以在孕妇和儿童中与寄生虫疾病有关的发病率的机制提供针对患者研究（POR）的初级教师的心态。第二个目标是通过允许她购买与职业目标相关的高级课程工作来为弗里德曼博士提供进一步发展自己的职业发展的时间。布朗大学分支机构医院提供了来自有兴趣在全球卫生领域进行POR的各个部门/部门的潜在指导的丰富来源。部门和机构为初级教职员工提供了大量直接支持。此外，尽管还有许多其他培训补助金，但仍有三项T32奖项，两个生物医学研究中心（Cobre）奖项（Cobre）奖项和一项T37，可以为弗里德曼（Friedman E.G.该提案的总体科学目标是提高研究阐明机制的研究，通过这种机制，母亲界面的免疫反应最终导致子宫，早产和新生儿铁不足的不良生长。受训者将能够利用大规模的特征性样本和结果，NIH资助的Praziquantel的随机对照试验，在菲律宾莱特（Leyte）妊娠12-16周妊娠。该试验于2012年12月结束，所有样品均可立即使用。我们将特别检查寄生抗原和微生物易位的作用，肠道中的微生物产物的过程进入了系统圆圈，因此在IUGR的发病机理，早产和新生儿铁不足的发病机理中引起了炎症。在人类疾病的背景下，尚无研究评估微生物转移（MT）。 Specifically, we will use this model to identify pathways through which MT and infection in these compartments affect placenal 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, menace 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研究中心与菲律宾的赠款，2）我们的R01（Pi Kurtis，Co-i Friedman）将在2015 - 16年度入学并关注主题，或3）作为他们自己在POR中的POR项目的一部分，并由Priore Training培训赠款和在菲律宾资助的现场，PI协作，PI曾与PI的良好现场进行了指导，在PI，PI的合作中，PI的成果很长一段。因此，她将能够对这种协作方法进行建模。