This goal of this short-term mentored senior career development award is to add to PI's research areas an understanding of the concepts, methods, and current research in epigenetics to his on-going work on biodevelopmental mechanisms that underlie observed social disparities and inequalities in health and development outcomes for children and through the life course. The particular focus will be on acquiring core knowledge on the current status of work on environmental influences expressed through epigenetic mechanisms, and laying the groundwork for extending that work to investigate epigenetic mechanisms in population samples that result from differential social influences. The training component of the award includes six components: interactions with the primary mentor, Dr. Hu, throughout the training period, in individual meetings and in research groups;participation in the primary research group focusing on these topics at the University of Michigan;participation in the core graduate course in Environmental Health Sciences that focuses on genomics and epigenomics in environmental health;execution of a research project to explore the impacts of social disparities, and possible epigenetic mediation, in an existing longitudinal database, a birth cohort that has been used to study toxicity and epigenetic effects;participation in a meeting of an international research network that involves the work of two leading figures in the study of socially driven epigenetic effects;extending PI's current familiarity with the ethical conduct of research into the areas of genomics and epigenomics, through review of current IRB protocols in this area and discussions with key researchers and IRB members.
The specific aim of the research to be conducted during this short-term career development award is to investigate the possible role of epigenetic mechanisms on the relationship between socioeconomic position (SEP) of the mother and child health outcomes of the offspring, through follow-up analyses of a longitudinal birth cohort. Although there has been extensive research on the effect of SEP on child developmental health (reviewed by Keating, 2009;Keating, in press b), there remain many questions about the mechanisms through which these effects operate. Second, there is a substantial body of research that indicates the role of epigenetic mechanisms on health outcomes arising from differential exposures in the physical environment, such as lead (Pilsner, Hu, et al., 2009;Wright et al., 2010). Third, there is an emerging research literature that suggests the probability that social environment exposures may also lead to epigenetic changes, which may in turn be linked to longitudinal health and development outcomes, in both animal and a few human studies (Szyf, McGowan, &Meaney, 2008). The current proposal aims to test the hyphothesis that variations in social status, which are putatively markers of maternal stress and stress buffers, are associated with epigenetic markers, which have been identified as being linked to the stress response system. Maternal social status will also be analyzed as a predictor of child health and development outcomes. If the direct relationships are observed as predicted, the epigenetic markers can be investigated as possible mediators of the SEP prediction of child outcomes.
The primary goal of this career development application and the included research component is to investigate epigenetic mechanisms underlying social disparities in life course health and development. Environmental effects on how genes function and are regulated have been found for a range of exposures, and these modifications of gene function can have substantial effects on subsequent health and development. Recent work has shown that the social environment can have similar epigenetic and health effects. The proposed work investigates the possible role of epigenetics in the production of social disparities in health and development. Understanding these mechanisms would provide important insights into, and possible remediation, the social determinants of population health.
