Dissecting gene dysregulation at the maternal-fetal interface in preeclampsia

剖析先兆子痫母胎界面的基因失调

基本信息

批准号：
10329277
负责人：
SUSAN J. FISHER
金额：
$ 2.51万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10329277
关键词：
Affect Award Bioinformatics Biology California Cancer Biology Career Mobility Cell Differentiation process Cells Communication Data Data Analyses Data Set Development Dimensions Disease Elderly Ensure Faculty Formulation Funding Future Gene Expression Profiling Genes Goals Grant Human Infertility Institution Laboratories Learning Location Mass Spectrum Analysis Maternal-Fetal Exchange Medical Research Medicine Mentors Mentorship Messenger RNA Mus Patients Physicians Placenta Placental Biology Placentation Play Pre-Eclampsia Principal Investigator Proteins Proteome Records Reproductive Biology Research Role San Francisco Scientist Syndrome Technology Testing Training Training Programs Translating Universities Uterus Woman Work Writing career career development college cytotrophoblast design differential expression endometriosis experience experimental study graduate student instrumentation meetings member novel outreach research and development responsible research conduct senior faculty single cell sequencing skills statistics success transcriptome tumor immunology

项目摘要

Abstract. The goal of the proposed research is for Dr. Alejandra Elder Ontiveros to obtain additional training in reproductive biology at the postdoctoral level. She received her MD degree from Escuela de Medicina Ignacio A. Santos, Instituto Tecnologico y de Estudios Superiores de Monterrey. Under the mentorship of Dr. Richard Behringer (Baylor College of Medicine), she recently completed her doctoral work studying uterine development in mice. Then she moved to the laboratory of Dr. Susan Fisher (University of California San Francisco, UCSF) where she is learning human placental biology and a powerful -omics technology—mass spectrometry (MS). In the award to which this supplement is appended, the Fisher group is testing the hypothesis that global gene expression profiling of cytotrophoblasts (CTBs) from placentas of preeclampsia (PE) patients will lead to the identification of novel molecules that play important roles in this syndrome. The impetus for this strategy is the finding that PE is consistently associated with aberrant differentiation of these cells, which translates into shallow placentation and the maternal signs of this syndrome. During the current segment of this R37 award, the group is using single cell sequencing to reveal disease-associated alterations in the developmental trajectories of differentiating CTBs. The goal of the experiments proposed in this application is to characterize the proteomes of CTBs isolated from the placentas of PE patients and control women, the same cells that are being subjecting to single-cell sequencing. The results will enable the addition of significant new dimensions to the latter work. First, the data will extend the findings from the mRNA to the protein level, important given the frequent lack of concordance between the two. Second, immunolocalization of the differentially expressed molecules in both datasets will pinpoint the exact location where the affected cells reside. This information will enable formulation of strategies for future experiments designed to test their functions. To further her career development, she will take classes (e.g., MS, bioinformatics, statistics, grant writing, mentorship and career advancement) and seek additional training experiences (e.g., responsible conduct of research, diversity and outreach). To hone her communication skills, she will regularly give presentations at UCSF and national meetings. Her research and career development will be overseen by an outstanding team of senior faculty with the relevant expertise indicated: Dr. Linda Giudice (human uterine biology, endometriosis, infertility), Dr. Robert Blelloch (cancer biology and immunology, mouse placental biology) and Dr. Steven Hall (mass spectrometry, including instrumentation and data analysis). All have distinguished mentoring and training records; two are physician scientists (Drs. Giudice and Blelloch). Their commitment to the candidate and the enthusiastic support of her primary mentor, Dr. Fisher, ensure the success of the training plan and the eventual launch of the candidate’s independent career as a faculty member and principal investigator at a top-tier medical research institution.

抽象的。拟议的研究的目的是让亚历杭德拉（Alejandra Elder Ontiveros）博士获得额外的培训博士后一级生殖生物学。她获得了Med Medicina Ignacio的MD学位 A. Santos，Instituto tecnologico y de esudios exporeses de Monterrey。在理查德博士的心态下 Behringer（贝勒医学院），她最近完成了学习子宫的博士学位工作小鼠的发展。然后她搬到了苏珊·费舍尔（Susan Fisher）博士（加利福尼亚大学圣San）弗朗西斯科（UCSF），她正在学习人类的生物学和强大的 - 质量技术 - 质量光谱法（MS）。在附加该补充剂的奖励中，Fisher Group正在测试假设来自先兆子痫的plecetas的全球基因表达分析（CTBS）（PE）患者将导致鉴定在该综合征中起重要作用的新分子。该策略的推动力是PE与这些策略的异常分化一致细胞，转化为浅的放置和该综合征的母体迹象。在电流期间该R37奖的部分，该组正在使用单细胞测序来揭示与疾病相关的改变在区分CTB的发展轨迹中。在此提出的实验的目标应用是为了表征从PE患者的plecetas分离的CTB的蛋白质组织和对照女性，正在接受单细胞测序的相同细胞。结果将使增加后来的工作有重要的新维度。首先，数据将从mRNA扩展到蛋白质水平，鉴于两者之间经常缺乏一致性，蛋白质水平很重要。其次，免疫定位两个数据集中不同表达的分子的不同细胞驻留。该信息将启用策略公式，以供未来的实验旨在测试其功能。为了进一步发展自己的职业发展，她将参加课程（例如MS，生物信息学，统计学写作，精神训练和职业发展）并寻求额外的培训经验（例如负责任进行研究，多样性和外展的进行）。为了亲爱的她的沟通技巧，她会定期给予在UCSF和国家会议上的演讲。她的研究和职业发展将由相关专家的高级教师团队表明：琳达·朱迪斯（Linda Giudice）博士（人子宫）生物学，子宫内膜异位症，不育症），罗伯特·布莱洛（Robert Blelloch）博士（癌症生物学和免疫学，小鼠斑点生物学）和史蒂文·霍尔（Steven Hall）博士（质谱，包括仪器和数据分析）。所有人都有杰出的心理和训练记录；两个是物理科学家（Giudice和Blelloch博士）。他们的对候选人的承诺和主要导师费舍尔博士的热情支持，确保培训计划的成功和候选人独立职业的活动启动的成功顶级医学研究机构的成员兼首席研究员。