The focus of our research is to identify mechanisms underpinning the biological embedding of stress, or ‘how stress gets under the skin’, and its effect on health and aging. Our research integrates the disciplines of molecular genetics, endocrinology, neurobiology and psychology. We employ multiple behavioral, physiological and molecular measurements to describe the stress response and its sequelae by using longitudinal observational studies and laboratory-based experiments. The goal of our research is to pinpoint behavioral and molecular targets for public health observation and clinical treatments aimed at understanding and mitigating the consequences of stress on health and aging.
Funded projects and collaborations of note include:
1) A recently funded NIH P50 grant, NIH CAPSTONE Center for Multidisciplinary Research and Training in Child Abuse and Neglect (P50HD089922) (Noll PI, Shalev Co-I, and in partnership with Pennsylvania’s Department of Human Services). A main goal of this center grant is to recruit a prospective cohort of 1,200 maltreated and comparison children, aimed at elucidating the multiple etiological processes believed to play a role in the onset and maintenance of adverse health outcomes for victims. Our lab receives blood, urine and saliva samples for processing and analysis. We are testing telomere length, telomerase activity, mitochondria-related markers, inflammatory cytokines and urine levels of catecholamine (epinephrine and norepinephrine), as well as omics measures of metabolomics and RNA sequencing.
(2) A recently funded NIH R21 grant, Temporal Genomics Mechanisms Underlying Disease and Aging (AG055621) (Shalev PI, Ram and Albert Co-Is). The goal of this project is to identify genomic mechanisms involved in young adults’ response to stress, as moderated by early adversity. Specifically, we are testing whether individuals exposed to early-life adversity show dysregulated changes in gene expression (via RNA sequencing) in response to a well-established laboratory stressor, compared with a no-stress condition, and compared with individuals without exposure to early adversity.
(3) An SSRI-funded project, Intergenerational Transmission of Trauma? Testing Cellular Aging in Mothers Exposed to Sexual Abuse and Their Children (Shalev PI, Noll Co-I). The overarching goal is to test the hypothesis of intergenerational transmission of trauma by measuring cellular aging in both mothers and children, members of the Female Growth and Development Study. Specifically, we are testing telomere length in mothers exposed to sexual abuse and their children.
(4) A CTSI-funded project, Complex interactions of behavior, genes, and environment in the multi-system characterization of the effects of sleep loss on health, cardio-metabolic disease risk, cognition, and the epigenome (Chang PI, Shalev Co-I). Its aim is to comprehensively characterize cardio-metabolic, cognitive, genomic, and epigenetic effects of sleep insufficiency in a controlled laboratory setting. Our role is to assist with the collection and sorting of blood samples for epigenetic methylation and whole-genome expression analysis. For this study, we are further investigating specific type of cells including monocytes and lymphocytes.
(5) A project funded by the Sara van Dam Foundation, Biological embedding of early-life experiences: How early-life experiences impact childhood development and can accelerate aging (Beijers, Radboud University, Netherlands PI, Shalev Co-I). Its aim is to test early-life factors associated with children’s socio-emotional development, cognition, and pubertal development. This includes biological-embedding mechanisms underlying this link. These research questions are being investigated in the Dutch BIBO-study (Basal Influences on the Baby Development): a prospective study in which 193 mothers and their children are followed from pregnancy until the last assessment at age 10. We are conducting all telomere length testing in children at both age 6 and 10 (N=170).
(6) A new BBH-funded project Integrating Dynamic Cellular Mechanisms with Momentary Assessments of Emotions (Shalev PI, Smyth and Lanza Co-Is). Day-to-day life affects biological processes, and vice versa, which in turn can influence health and aging processes over time. This research is being done to find out how morning gene expression in midlife adults affect how negative and positive emotions vary throughout the day using ecological momentary assessments. We further collect indicators of perceived stress levels to test whether past, present and anticipatory stress moderate the association between gene expression and emotions.