The following description was taken from the R01 version of this FOA.
The placenta is critically important for the health of both mother and developing fetus. Abnormalities of placental development and function are known to underlie many major pathologies of pregnancy including spontaneous preterm birth, fetal growth restriction, and preeclampsia. The assessment of the placenta across pregnancy presents special challenges due to the need to avoid risk to the mother and developing fetus. Thus, most information on human placental biology is obtained by studying placental tissue obtained after delivery from pathological pregnancies, such as preterm deliveries occurring predominately in the third trimester, from term deliveries in which placental development has already crested, or from in vitro model systems. There is a paucity of information obtained earlier in gestation when many of the pregnancy pathologies are believed to have their origins, and limited information gleaned throughout gestation from normal pregnancies.
The Human Placenta Project (HPP) is an initiative aimed at revolutionizing our understanding of the human placenta. By accelerating the development and application of innovative technologies, development of novel biomarkers which reflect placental status, and application of in-depth analysis of existing data and sample collections, researchers will be able to produce a new dynamic picture of placental structure and function in real time, one that assesses key developmental trajectories of placental formation and functional cues that are critical for successful human pregnancy. It is expected that the insights resulting from these approaches will ultimately lead to new ways to treat, cure, and even prevent placental dysfunction disorders such as preeclampsia, fetal growth restriction, spontaneous preterm birth, and stillbirth. Given the requirements for these developments, it is likely that the methods developed will also be applicable to assessment of other internal organs, thus the impact may be far reaching.
The goal of this initiative is to stimulate development of novel tools and approaches to assess human placental structure and function in vivo across pregnancy. This will provide valuable clinical and research tools to enhance our understanding of placental biology and improve our clinical management of pregnant women.
Scope of Research to be Performed
This FOA is for the development of novel methods for studying the placenta in vivo with the ultimate goal of human use across pregnancy. Special consideration will be given to applications that develop methods that are applicable throughout pregnancy, preferably starting in early gestation during the period of trophoblast invasion and remodeling of the uterine spiral arteries, and which also establish reference values.The placenta is a dynamic organ which changes over the course of pregnancy. To be helpful, assessments need to yield results within a time frame that reflects the current structural/functional status. However, real-time is not meant to imply instantaneous results.
All proposed research teams must include at least one obstetric clinician to provide insights into current or potential clinical functional or safety limitations of the chosen technology. They should have sufficient involvement to ensure that the proposed technology would be feasible in a clinical setting. It is strongly recommended that the team also include a member with specific expertise in placental biology. The range of additional disciplines included may be either broad or relatively narrow (e.g., various subspecialties within a given field) as appropriate to the scientific goals of the application. The application should reflect the expertise of the proposed team. Strong academic-industrial partnerships are welcomed.
The rapid advancement of research in this area through data sharing is a priority for the HPP. Applicants are encouraged to share their data in real time to magnify the potential impact of their work through dissemination to the scientific community. NIH data sharing guidance is provided at this link: http://grants.nih.gov/policy/sharing.htm
General Technology Characteristics
This FOA promotes the development of breakthrough tools and technologies to enable real-time measurement of human placental processes that are currently relatively inaccessible during pregnancy and to assess changes in these processes as development progresses, including but not limited to:
- Anatomic and structural changes of the placenta across development.
- Villous cell structure and function.
- Blood flow, oxygenation, diffusion and perfusion within the placenta.
- Maternal-fetal nutrient transfer across the placenta.
- Metabolic changes within the placenta including, but not limited to, oxygenation, oxidative stress, choline, lipids and lactate, and including measures of placental proteins and gene expression.
- Placental barrier (targeted, regional) permeability and function in the human placenta.
- Regulation of maternal and fetal immunologic function involved in placental processes.
There is high interest in applications focused on the development of biosensors and devices capable of multiplex analysis of molecules that reflect placental status from small samples of non-blood sources including saliva, breath, urine or vaginal secretions.
For purposes of validating novel technologies for measurement of circulating factors, any placental molecules utilized do not need to be predictive of abnormal placental function, but there should at least be potential for adding novel predictive biomarkers. Applications proposing discovery of biomarkers as a byproduct of technology development and testing are allowed. However, applications whose primary focus is on biomarker discovery will be given low priority. Investigators interested in focusing on placental biomarker discovery should consider other funding opportunities.
Solutions describing existing, well-established and/or currently supported approaches, especially commonly used strategies, are not of interest unless a compelling case is made that significant, quantifiable advances are proposed, and/or the methods and measures are used in unique combinations not previously tested together for the real-time assessment of human placental structure, development, and function.
Projects that are considered low priority for this FOA include:
- Development of technologies that can only be applied in the third trimester of pregnancy or postpartum.
- Projects that only focus on data collection, data processing, data analysis, and computational modeling and simulation without technology development.
- Basic research and studies of disease mechanisms that are not part of technology validation.
- Projects directed at understanding placental biology without the development of novel technology to assess placental structure or function in real-time.
- Development of technology that has little potential for utility in late first trimester-early second trimester unless the conditions listed below are met.
- Development of projects whose primary focus is on the collection and analysis of imaging or omics data for biomarker identification or validation.
- Development of methods for isolation of placental vesicles or other circulating factors unless done in association with transformative assessment approaches.
- Development of methodologies or technologies that are contraindicated for use in human pregnancy.
- Projects in non-mammalian systems that have little potential to be applied to human placenta imaging or assessment.
This funding opportunity is to facilitate development of novel technology that may be used across pregnancy for assessment of placental structure and/or function. Achievement of this goal may require the use of multiple approaches and some may not be able to be utilized within the first trimester at this time. Projects which are directed at development of technologies with little potential for use in the first trimester will be considered, provided:
- The reason(s) it cannot be used in the first trimester is detailed.
- The potential for use in the first trimester is addressed.
- The value of the technology to the goals of the Human Placenta Project is justified.
It is recognized that development of these novel technologies may require use of animal models. Studies carried out exclusively in animals may be proposed; however, the pathway for translation into humans and potential safety and technical issues associated with human application of the technology/tools must be clear.
As the goal of this FOA is to support research-driven technology development to meet the objectives of the HPP, program priority will be given to applications that are exceptional in the following aspects: 1) potential for safe in-vivo placental assessment during gestation, 2) the level of innovation, 3) the uniqueness within the portfolio of currently supported HPP projects, 4) the expected timeline for human applicability. Funds requested must be used primarily to support technology development and validation.
Potential applicants are advised to consult with the Scientific/Research contact listed in Section VII for appropriateness of submission to this FOA.
Deadlines: December 4, 2018, December 4, 2019, December 4, 2020
- R01 –
- R21 –
Filed Under: Funding Opportunities