Integrated Transporter Elucidation Center

项目概要/摘要 鉴于其理化性质，药物和膳食补充剂通常需要使用 溶质载体（SLC）和ATP结合盒（ABC）转运蛋白跨越滋养层屏障。这些相同 转运蛋白也参与向胎儿输送营养物质， 怀孕期间的治疗可能会破坏这些共享系统。因此，了解 SLC和ABC转运蛋白在胎盘药物和营养物质配置中的相互作用是优化 改善围产期保健的治疗干预措施。我们的研究团队一直致力于 研究胎盘中SLC和ABC转运蛋白的新方法。为了扩大这些努力，我们创建了 综合转运蛋白阐明中心（InTEC），利用跨4个领域的转化研究专业知识， 学术机构我们的中心假设是胎盘转运蛋白的新调节和功能 可以使用综合实验，流行病学和建模方法来阐明。在一起， 所产生的数据和模型可以预测治疗剂和营养物的胎盘处置及其 对胎儿发育的后续影响。为了实现这一目标，我们将1）确定调节的关键因素 胎盘转运蛋白，使用最先进的定量靶向绝对蛋白质组学和遗传学，在美国的 出生队列; 2）开发一种新的计算建模框架，预测母胎化学处置 根据胎盘转运蛋白的功能和调节;和3）评估SLC和ABC转运在新的 胎盘芯片微生理系统我们将测试营养素，补充剂，药物和有毒物质， 胎盘转运蛋白的底物和抑制剂。InTEC将实现胎盘转运蛋白的快速加速 研究和建立转运生物学的最佳做法。资源和数据集将通过 CIIPro门户网站创建于2017年。将为早期职业科学家提供独特的培训机会 （本科生，MS/MPH/博士生和博士后研究员）和临床医生（产科住院医师和 研究员）在药理学，计算生物学，公共卫生，母胎医学， 生物医学工程通过创新的研究和培训，InTEC将导致创新的突破， 在胎盘运输领域，确保有一支训练有素的劳动力队伍，以改善孕产妇和围产期健康。

PROJECT SUMMARY/ABSTRACT Given their physiochemical properties, medications and dietary supplements often require active transport using solute carriers (SLC) and ATP-binding cassette (ABC) transporters to cross trophoblast barriers. These same transporters are also involved in the delivery of nutrients to the fetus and one unintentional consequence of drug therapy during pregnancy can be disruption of these shared systems. Therefore, understanding the interplay between SLC and ABC transporters in the placental disposition of drugs and nutrients is one key step to optimizing therapeutic interventions that improve perinatal healthcare. Our research team has championed the advancement of novel approaches to study SLC and ABC transporters in the placenta. To expand these efforts, we have created the Integrated Transporter Elucidation Center (InTEC) which leverages translational research expertise across 4 academic institutions. Our central hypothesis is that novel regulation and functions of placental transporters can be elucidated using integrated experimental, epidemiological, and modeling approaches. Together, data and models generated can predict the placental disposition of therapeutics and nutrients and their subsequent effects on fetal development. To accomplish this goal, we will 1) identify critical factors that regulate placental transporters using state-of-the-art quantitative targeted absolute proteomics and genetics in a US-based birth cohort; 2) develop a novel computational modeling framework that predicts maternal-fetal chemical disposition according to placental transporter functions and regulation; and 3) evaluate SLC and ABC transport in novel placenta-on-a-chip microphysiological systems. We will test nutrients, supplements, drugs, and toxicants as substrates and inhibitors of placental transporters. InTEC will enable rapid acceleration of placenta transporter research and establish best practices for transporter biology. Resources and datasets will be disseminated via our CIIPro webportal created in 2017. Unique training opportunities will be provided to early career scientists (undergraduate students, MS/MPH/PhD students, and postdoc fellows) and clinicians (obstetrics residents and fellows) at the intersections of pharmacology, computational biology, public health, maternal-fetal medicine, and biomedical engineering. Through innovative research and training, InTEC will lead to novel breakthroughs in the field of placental transport and ensure a well-trained workforce to improve maternal and perinatal health.