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（由申请人提供）：该 K24 提案有两个主要目标。首先是为候选人 Jennifer Friedman（医学博士、哲学博士）提供时间，为初级教师提供以患者为导向的研究 (POR) 的指导，解决孕妇和儿童寄生虫病相关的发病机制。第二个目标是为弗里德曼博士提供时间，让她能够学习与职业目标相关的高级课程，以进一步发展自己的职业生涯。 布朗大学附属医院提供了来自多个部门/部门的丰富的潜在学员来源，为有兴趣在全球卫生领域开展 POR 的初级教师提供住宿。院系和机构为初级教师开展 POR 提供重要的直接支持。此外，尽管还有许多其他培训补助金，但还有三项 T32 奖、两项生物医学研究卓越中心 (COBRE) 奖和一项 T37 奖，该奖项可以专门为弗里德曼博士感兴趣的研究领域（例如被忽视的热带病、传染病发病机制和围产期生物学）进行 POR 的初级教师提供资金。 该提案的总体科学目标是推进研究，阐明母胎界面的免疫反应最终导致子宫内生长不良、早产和新生儿铁不足的机制。学员将能够利用 NIH 资助的、在菲律宾莱特岛妊娠 12 - 16 周时进行的大规模吡喹酮随机对照试验的特征良好的样本和结果。试验于 2012 年 12 月结束，所有样品均可立即使用。我们将专门研究寄生抗原和微生物易位的作用，微生物产物从肠道进入体循环的过程，以及随之而来的炎症在 IUGR、早产和新生儿铁不足的发病机制中的作用。尚无研究评估人类妊娠疾病中的微生物易位（MT）。具体来说，我们将使用该模型来确定这些区室中的 MT 和炎症影响胎盘和新生儿 IGF 途径和铁转移的途径，以及这最终如何影响胎儿生长和铁禀赋。虽然这些科学目标非常详细地提供，以提供候选人感兴趣的领域和专业知识的示例，但受训者还将参与菲律宾的直接受试者注册、评估和长期随访，作为 1) 我们的热带医学和 研究中心向菲律宾提供资助，2) 我们的 R01（PI Kurtis，Co-I Friedman）将在 2015-16 年招募和跟踪受试者，或 3) 作为他们自己的全球卫生 POR 项目的一部分，该项目得到上述培训拨款的支持，并在菲律宾莱特岛一个资金充足的地点进行，PI 在那里进行了长期且富有成效的合作。因此，她将能够模拟这种协作方法。