2018 — 2021 |
Borders, Ann E.b. Miller, Gregory Evan |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Understanding Socioeconomic Disparities in Perinatal Risk: the Role of Epigenetic and Transcriptional Regulation in the Placenta @ Northwestern University
This application is a response to PAR #16-355 ?Social Epigenomics Research Focused on Minority Health and Health Disparities.? In the contemporary United States, children's outcomes vary substantially by their family's socioeconomic status (SES). These disparities are present in multiple domains, including cognitive development, psychiatric disorders, and physical health. As low-SES youth mature into adulthood, they continue to have disproportionately poor outcomes, as reflected in poverty rates, mental health problems, and morbidity and mortality from chronic diseases associated with aging. Social science has identified a variety of structural, contextual, and psychological factors that contribute to these disparities. But we have only a superficial understanding of how these factors ?get under the skin? to influence biological processes that are proximally involved in brain maturation, health problems, and other outcomes that pattern by SES. Recently, theorists have addressed this question by posting that socioeconomic disadvantage gets biologically embedded during gestation, a sensitive period when multiple organ systems are developing. Animal models show that gestational influences of this sort are possible, and mediated in significant part through modulation of epigenetic and transcriptional processes in the placenta. Nevertheless, studies have yet to comprehensively examine the plausibility of the embedding hypothesis in human subjects. We seek to fill this gap here by recruiting an economically diverse sample of 700 women during pregnancy, and characterizing multiple dimensions of their lifecourse socioeconomic conditions. At delivery, we will biopsy women's placentas, and measure gene regulation in a biologically integrated fashion by assaying patterns of DNA methylation (DNAm), and expression of microRNA (miRNA) and messenger RNA (mRNA). We hypothesize that to the extent that women are lower in SES, their placental biopsies will show epigenetic and transcriptional patterns indicative of lower fetal tolerance, greater immune activation, and slower organ maturation. Using data from geocoding, interviews, and questionnaires, we also will develop a multilevel framework. It will specify connections between features of neighborhoods (economic deprivation, violent crime, residential segregation, social capital), families (job instability, financial duress, relationship qualities), and individuals (depressive symptoms, pregnancy anxiety, lifestyle factors), and characterize the strength and nature of their associations with dimensions of placental gene regulation, i.e., DNAm, miRNA, and mRNA. Finally, we will clarify the clinical implications of these patterns by examining their connections to preterm birth and growth restriction. We hypothesize that lower SES women will experience higher incidences of both conditions relative to higher SES women. Using mediation analyses, we will attempt to identify molecular pathways that contribute to these disparities, with an emphasis on chronic inflammatory lesions in the placenta, and epigenetic and transcriptional modifications that initiate and/or maintain them.
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1 |
2020 — 2021 |
Miller, Gregory Evan |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Research Support Core
PROJECT SUMMARY: Research Support Core We propose a Research Support Core (RSC) in the context of a P50 Research Center of Excellence: The Center for Translational and Prevention Science (CTAPS). The RSC?s overarching goal is to facilitate a new generation of research focused on (a) stress-induced alterations in brain-immune signaling that create vulnerabilities to substance misuse and cardiometabolic disease, (b) the identification of malleable protective processes that can prevent or mitigate the downstream health consequences of stress, and (c) the development of interventions for African Americans that prevent substance misuse and cardiometabolic disease. To this end, the Research Support Core (RSC) will: (a) oversee and execute analyses of neurocognitive, inflammatory, cardiometabolic, and biostatistical data collected by Center Research Projects (RPs) and Pilot Studies; (b) provide intellectual consultation to Center scientists regarding design protocols, promising targets for research and intervention, and interpretation of results; and (c) sponsor educational and training experiences for CTAPS scientists and the broader scientific community. This Core represents a continuation of a highly productive collaboration between scientists at the University of Georgia and Northwestern University, who together have established pipelines for generating inflammatory, cardiometabolic, and neuroimaging data relevant to African Americans? substance use and overall health. The RSC comprises substantial intellectual capital and state-of-the science facilities for analysis of neuroimaging data and assaying biomarkers of inflammatory and cardiometabolic functioning. It is composed of three subscores: Neurocognitive (NCO), Inflammatory (INF), and Biostatistical (BSC). The RSC?s aims are to: (1) provide intellectual consultation to RP directors, transdisciplinary work groups, and pilot project investigators, (2) help develop protocols for collecting high-quality neuroimaging, inflammatory, and cardiometabolic data, (3) assay biospecimens for inflammatory and cardiometabolic biomarkers, (4) process and analyze data collected in neuroimaging paradigms, and (5) provide educational experiences to CTAPS scientists, mentees, and affiliates, as well as serving as a resource for the scientific community by providing education through online seminars and preconference workshops.
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0.948 |