The focus of our research is to understand the mechanistic linkage between early developmental and environmental factors, stress-related biological systems, and health outcomes. We employ multiple behavioral, physiological and molecular measurements to describe the stress response and its sequelae by using longitudinal observational studies, deep phenotyping techniques and laboratory-based experiments. The goal of this research is to pinpoint behavioral and molecular targets for public health observation and clinical treatments.
Selected projects and collaborations of note include:
(1) A National Institute of Child Health and Human Development (NICHD) Specialized Center Grant (2 P50 HD089922; 06/05/2023 – 03/31/2028; Noll PI, Shalev Co-I). Through a large-scale partnership with the State of Pennsylvania’s Department of Human Services, a main goal of this center grant, NIH CAPSTONE Center for Multidisciplinary Research and Training in Child Abuse and Neglect, is to recruit a large prospective cohort of 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 in victims. To investigate the biological embedding of child maltreatment, our lab processes and analyzes blood, urine and saliva samples to determine telomere length, telomerase activity, mitochondria-related markers, as well as omics measures of DNA methylation, metabolomics and RNA sequencing. This renewal (Phase 2) will capitalize on the successes of Phase 1 by providing continuity in the cutting-edge, observational cohort study (Project 1) to, in turn, fill a critical gap in child maltreatment research—namely, variable pathways into and through the transition to adulthood.
(2) A National Institute on Aging (NIA) Small Grant Program (R03 AG081719; 04/15/2023 – 03/31/2025; Graham-Engeland PI, Shalev Co-I). The aim of the project, The role of loneliness in cognitive decline and risk for dementia, is to examine the longitudinal relationships of loneliness and biomarkers of Alzheimer’s disease, neurodegeneration, and brain-derived neurotrophic factor in humans, to identify neurobiological mechanisms contributing to increased cognitive decline and dementia risk of lonely individuals.
(3) A National Institute on Aging (NIA) Small Grant Program (R03 AG071549; 02/01/2022-06/30/2024; Shalev PI). The aim of the project, Telomere Length Analysis in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) Study, is to conduct new telomere length assays of stored biospecimens from the CALERIE™ trial, the first ever randomized human trial of long-term caloric restriction. We will use new telomere length data to test if caloric restriction slows the rate of cellular aging in humans and explore putative biological mechanisms. Overall, the project will advance efforts to improve mechanistic understanding of how caloric restriction influence telomere length in humans, which could pinpoint new targets for anti-aging therapies.
(4) A National Institute of Nursing Research (NINR) Research Project Grant (R01 NR019610; 09/09/2021 – 06/30/2026; Garrett-Peters & Shalev MPI). The project, Early Life Adversity and the Developmental Programming of Early Childhood Telomere Biology: A Longitudinal Study of Developmental Context and Behavioral Mediators, proposes an interdisciplinary examination of the effects of prenatal and postnatal early life adversity on accelerated biological aging via telomere erosion and DNA methylation across infancy and toddlerhood. In addition, the project aims to explore how proximal developmental experience (parenting) and child behavior (self-regulation) may mediate these associations.
(5) A National Institute on Aging (NIA) Research Project Cooperative Agreement (U01 AG073204; 09/05/2021-08/31/2024; Martin & Redman MPIs, Shalev Co-I). The aim of the project, A Planning Project to Pilot Test and Optimize Dietary Approaches to Slow Aging and Design a Long-Term Trial, is to determine the feasibility and preliminary efficacy of two caloric restriction and two time-restricted eating interventions to modulate healthspan and biomarkers of aging in young (25-45 years) individuals.
(6) A National Institute on Aging (NIA) Research Program Project Grants (P01 AG003949; 2/15/2022-3/31/2027; Engeland & Graham-Engeland MPIs, Shalev Co-I). This longitudinal study (5 annual data waves), Depression, Inflammation, Biological Age and Cognitive Function will examine how depression, inflammation, and biological aging (telomere length, DNA methylation) interact to predict cognitive decline, mild cognitive impairment, and dementia (e.g., Alzheimer’s disease) in 767 participants 60+ years of age in the Bronx, NY.
Recently completed projects:
(7) A National Institute of Environmental Health Sciences (NIEHS) Research Project Cooperative Agreement (U01 ES030949; Shalev PI). The aim of the project, The Comparability and Reproducibility of Telomere Length Measurements for Population-based Studies, is to improve methodological understandings by investigating how different tissues and processing techniques contribute to variation in determined telomere length from birth to old age. This proposal will fill critical gaps in the field by testing salient methodological aspects to help reveal optimal tissue cells for population-based research, clarify technical laboratory procedures, enable comparison between measurement methods, and advance a set of guidelines for measuring telomere length as part of the Telomere Research Network consortium.
(8) A National Institute on Aging (NIA) Exploratory/Developmental Research Grant Award (R21 AG05562; Shalev PI). The aim of the project, Temporal Genomics Mechanisms Underlying Disease and Aging, is to identify genomic mechanisms involved in young adults’ response to stress, as moderated by early adversity. We are testing whether individuals exposed to early-life adversity show dysregulated changes in gene expression in response to a well-established laboratory stressor, compared with a no-stress control condition, and compared with individuals without exposure to early adversity.
(9) A project funded through the Sara van Dam Foundation (Beijers, Radboud University, Netherlands PI, Shalev Co-I), Basal Influences on the Baby Development. This prospective study followed 193 mothers and their children from pregnancy until the last assessment at age 10. Its aim is to test early-life factors associated with children’s socio-emotional development, cognition, and pubertal development, including molecular mechanisms underlying this link such as telomere length and epigenetics.