Candidate: The PI is a Research Assistant Professor and nutritional epidemiologist whose primary career goal is to apply epigenetic approaches to improve the understanding of the interplay of sleep/circadian rhythms and nutrition on long-term cardiometabolic health risk. The proposed award includes a 5-year plan of training and research centered on circadian rhythms, epigenetics, study design, and skills required to lead a research team. Research context: Insufficient and mistimed sleep is recognized as a risk for adverse cardiometabolic outcomes. Adolescents are especially vulnerable as they have high prevalence of both short sleep duration and misaligned sleep timing. Yet, the unique contributions of sleep duration and circadian misalignment to cardiometabolic risk is unclear. Uncovering the epigenetic mechanisms behind these relationships is a highly promising avenue for this public health issue. Recent cross-sectional evidence shows that epigenetic alterations of metabolic and circadian genes might play an intermediary role in the relationships between sleep/circadian rhythms and cardiometabolic health, yet longitudinal investigations are scarce. The application of epigenetic approaches to identify potential mechanisms that link sleep to cardiometabolic health is novel. Research Objectives:
The aims are two-fold: 1) to evaluate the independent associations of sleep duration and timing with cardiometabolic health among adolescents and 2) to examine epigenetic associations between insufficient/mistimed sleep and cardiometabolic health. Research Plan: The PI will analyze existing data from an NIH-funded established cohort study of adolescents in Mexico City with highly variable sleep patterns (some participants' sleep patterns are constrained by morning school shifts while others have more flexibility due to an afternoon school shift). Associations between objectively collected sleep data (7-days of actigraphy) and cardiometabolic biomarkers (adiposity, blood pressure, and insulin resistance collected at two time points 24 months apart) will be analyzed. Stored leukocytes will be used to measure gene expression and epigenome-wide DNA methylation. Longitudinal and epigenome-wide statistical analyses will be conducted. Career Goals and Development: The PI will gain expertise in assessment of circadian rhythms, epigenetics laboratory investigation, and epidemiological study design through didactic and hands-on experiences. She will also advance in her leadership, mentorship, and grantsmanship skills, and by the end of the training period will apply for an R01 centered on sleep/circadian rhythms, nutrition, and epigenetics. Environment: Resources available to the PI include a well-rounded and supportive team of mentors representing the fields of sleep/circadian rhythms, epigenetics, nutrition and cardiometabolic health; and the excellent research infrastructure at the University of Michigan School of Public Health where the PI has been guaranteed 80% of time devoted to the research goals delineated in the proposal.
Adolescence is a vulnerable time period when insufficient and mistimed sleep may affect cardiometabolic risk factors including adiposity, high blood pressure, and insulin resistance. To understand which aspects of sleep to intervene on, there is an urgent need to disentangle the independent contributions of short sleep duration and delayed sleep timing (proxy for circadian rhythm misalignment) to cardiometabolic risk. Examining the epigenetic pathways that link sleep duration and timing with prospective cardiometabolic risk provides a novel way to distinguish these relationships and to gain mechanistic insights.
