Placental malaria: The role of inflammation at the maternal-fetal interface

胎盘疟疾：母胎界面炎症的作用

基本信息

批准号：
10524011
负责人：
Stephanie Lina Gaw
金额：
$ 19万
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：
2018-12-04 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10524011
关键词：
Adverse effects Affect Africa South of the Sahara Anemia Antigens Area Award Basement membrane Bathing Bioinformatics Biopsy Birth Weight Blood Blood Vessels Blood specimen California Cells Childhood Chorionic villi Chronic Circulation Clinical Complement Data Developing Countries Embryo Equilibrium Erythrocytes Falciparum Malaria Fetal Growth Fetal Growth Retardation Fetus Gene Expression Profiling Genes Goals Gravidity Growth Hormones Human Hypertension Immune Immune response Immunity Infection Infection Control Inflammation Inflammatory Inflammatory Response Innate Immune Response Interferon Type I Interferon Type II Interferons International Invaded Life Cycle Stages Liver Low Birth Weight Infant Macrophage Malaria Maternal Mortality Maternal-Fetal Exchange Maternal-fetal medicine Mediating Mentors Mesenchymal Modeling Molecular Morbidity - disease rate Mothers Myometrial Nature Nutrient Organ Outcome Parasites Pathologic Pathway interactions Penetration Perinatal mortality demographics Placenta Placental Biology Placentation Plasmodium falciparum Play Population Positioning Attribute Pre-Eclampsia Predisposition Pregnancy Pregnancy Complications Pregnancy Histories Pregnancy Outcome Pregnant Women Premature Birth Prevention strategy Process Regulation Research Personnel Resource-limited setting Risk Role Sampling San Francisco Small for Gestational Age Infant Spontaneous abortion Stromal Cells Structure Surface Syncytiotrophoblast Testing Therapeutic Intervention Time Training Trees Uganda Universities Uterus Villous Villus Vulnerable Populations Work angiogenesis cell type cytotrophoblast design differential expression embryo/fetus experimental study fetal genetic signature hormone regulation immunoregulation in vitro Model individual response innovation interstitial laser capture microdissection malaria infection migration mortality multidisciplinary neonatal death neonate new therapeutic target perinatal outcomes placental malaria pregnancy disorder professor programs response skills stem cells theories therapeutic target transcriptome transcriptome sequencing translational immunology translational study transmission process uptake wasting

项目摘要

PROJECT SUMMARY This is an application for a K08 for Dr. Stephanie Gaw Valderramos, an Assistant Professor in Maternal- Fetal Medicine at the University of California at San Francisco who is establishing herself as a young investigator in multidisciplinary translational studies of placental malaria. This award will provide Dr. Valderramos with the support necessary to test the theory that placental malaria causes local inflammatory changes in the placenta, leading to dysregulation of placental function and consequently fetal growth restriction. To achieve this goal, Dr. Valderramos has assembled a mentoring team comprised of Dr. Susan Fisher, an expert in placental biology; Dr. Philip Rosenthal, an international expert in translational studies of malaria; and Dr. Margaret Feeney, an expert in pediatric immune responses to malaria. Little is known about placental development in the setting of malaria, despite fact that maternal infection is responsible for up to 35% of low birth weight infants, and that in high transmission areas, up to 70% of fetal growth restriction cases and 36% of preterm deliveries are attributable to malaria in pregnancy. In placental malaria, P. falciparum-infected red blood cells accumulate in the maternal intervillous spaces of the placenta. It is believed that the inflammatory response to infection underlies the mechanisms by which placental malaria leads to fetal growth restriction; however, the consequences of the differential inflammatory signatures in remain unexplored. Dr. Valderramos’ recent work has shown that maternal and fetal macrophages have distinct gene responses to placental malaria. These differences correlate with birth weight, and depend on the mother’s pregnancy history, suggesting a new explanation for the increased susceptibility to pregnancy complications seen in first-time mothers. She will test the hypothesis that the type I interferon pathway plays an important role regulating the balance between inflammation and immunity in placental malaria, and that more severe dysregulation of this inflammatory response may have a greater negative impact on placental development and pregnancy outcome. Specifically, she will 1) apply a combination of laser capture microdissection and RNAseq approaches to placental biopsies (malaria cases vs. controls) she collected in Uganda, which will enable global transcriptional profiling of immune and other responses of individual placental cell types; and 2) test the effects of differentially expressed molecules that could impact placental development using in vitro models of this process. These studies will identify new targets for therapeutic intervention. Through a focused program of mentored training and coursework, the she will develop advanced skills in placental biology, bioinformatic analysis, translational immunology, and the design and conduct of translational studies of malaria in resource-limited settings. At the completion of this award, Dr. Valderramos will be well positioned to develop an R01 application to further define correlates and mechanisms of pathologic inflammatory responses to placental malaria.

项目摘要这是针对Stephanie Gaw Valderramos博士的K08的申请，母亲的助理教授加利福尼亚大学旧金山分校的胎儿医学正在建立自己的年轻胎盘疟疾多学科翻译研究研究者。该奖项将为博士提供。瓦尔德拉摩斯（Valderramos plapeta的变化，导致位置功能失调，从而导致胎儿生长限制。为了实现这一目标，Valderramos博士召集了一支由Susan博士完成的心理团队费舍尔（Fisher），专家占地生物学；菲利普·罗森塔尔（Philip Rosenthal）博士，国际翻译研究专家疟疾;儿科免疫反应的专家玛格丽特·费尼（Margaret Feeney）博士。鲜为人知关于疟疾环境中的位置发展，遗产感染负责的使命事实低出生体重婴儿的35％，而在高传输区域中，胎儿生长的70％限制病例和早产的36％归因于怀孕的疟疾。到位疟疾，恶性疟原虫感染的红细胞积聚在孕妇的介化空间中胎盘。据信，对感染的炎症反应是基于其机制的胎盘疟疾导致胎儿生长限制；但是，差异的后果炎症签名仍然出乎意料。 Valderramos博士最近的工作表明，胎儿巨噬细胞对疟疾的基因反应不同。这些差异与出生有关体重，并取决于母亲的怀孕史，这暗示了增加的解释在初次母亲中看到的对怀孕并发症的敏感性。她将检验以下假设 I型干扰素途径在调节注射和之间的平衡方面起着重要作用斑点疟疾的免疫力，这种炎症反应的更严重失调可能具有对胎盘发育和妊娠结局的负面影响更大。具体来说，她将1）申请激光捕获显微解剖和RNASEQ的组合，用于放置活检（疟疾）她在乌干达收集的案件与控制），这将使全球免疫转录分析和单个位置细胞类型的其他反应； 2）测试不同表达的效果可能会使用此过程的体外模型影响斑点发育的分子。这些研究会确定治疗干预的新目标。通过专注的指导培训计划和课程工作，她将发展占地生物学的高级技能，生物信息学分析，翻译免疫学，以及在资源有限的环境中疟疾翻译研究的设计和行为。该奖项的完成，Valderramos博士将有能力开发R01申请进一步定义的病理炎症反应对斑点疟疾的相关性和机制。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vaginal birth after cesarean: Does accuracy of predicted success change from prenatal intake to admission?

DOI：
10.1016/j.ajogmf.2020.100094
发表时间：
2020-05-01
期刊：
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
影响因子：
6.3
作者：
Ha, Thoa K.;Rao, Rashmi R.;Gaw, Stephanie L.
通讯作者：
Gaw, Stephanie L.

Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants.

人类胎盘外植体中对 COVID-19 mRNA 疫苗暴露的最小 mRNA 摄取和炎症反应。

DOI：
10.1101/2023.02.01.23285349
发表时间：
2023
期刊：
medRxiv : the preprint server for health sciences
影响因子：
0
作者：
Gonzalez,Veronica;Li,Lin;Buarpung,Sirirak;Prahl,Mary;Robinson,JoshuaF;Gaw,StephanieL
通讯作者：
Gaw,StephanieL

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy.

DOI：
10.1038/s41467-022-32188-1
发表时间：
2022-07-30
期刊：
Nature communications
影响因子：
16.6
作者：
通讯作者：

Analysis of placental pathology after COVID-19 by timing and severity of infection.

DOI：
10.1016/j.ajogmf.2023.100981
发表时间：
2023-07
期刊：
American journal of obstetrics & gynecology MFM
影响因子：
6.3
作者：
通讯作者：

Nirmatrelvir-Ritonavir (Paxlovid) for Mild Coronavirus Disease 2019 (COVID-19) in Pregnancy and Lactation.

Nirmatrelvir-Ritonavir (Paxlovid) 用于治疗妊娠期和哺乳期轻度冠状病毒病 2019 (COVID-19)。

DOI：
10.1097/aog.0000000000005152
发表时间：
2023
期刊：
Obstetrics and gynecology
影响因子：
7.2
作者：
Lin,ChristineY;Cassidy,AriannaG;Li,Lin;Prahl,MaryK;Golan,Yarden;Gaw,StephanieL
通讯作者：
Gaw,StephanieL