Existing health disparities are at least partially rooted in the impact of experiences of chronic psychosocial and environmental stress (cPSES) over the life course and its subsequent effects on human biology. Activation of the hypothalamus-pituitary-adrenal and sympathetic nervous system axes by cPSES leads to increases in catecholamines and subsequent sustained release of inflammatory cytokines, both modulating immune cells, including Natural Killer (NK) cells. The hypothesis is that NK cell function is modulated during chronic stress through the sustained impact of catecholamines and inflammatory cytokines.
Dr. Saurabh’s team aims to evaluate the impact of catecholamines, cytokines, and their combination on NK cells utilizing in vitro studies and samples from a community-engaged cohort of Black/African American women who are at disproportionally high risk for obesity and cardiovascular disease. Long-term exposure of NK-92 cells to catecholamines and/or cytokines will be performed, mimicking the impact of chronic stress in cell culture. Subsequently, assays determining NK cell function and analysis of involved pathways will be performed using degranulation assays as well as RNA sequencing, proteome analysis, flow cytometry, and ELISA-based techniques.
Additionally, Dr. Saurabh’s team will evaluate associations between NK cell function, levels of catecholamines/cytokines, and measures of cPSES using data and samples from a community-engaged pilot study among Black/African American women from socioeconomically under-resourced neighborhoods in Washington, D.C.
In accordance with the NIMHD framework, Dr. Saurabh’s team hopes to gain valuable insight into the biological vulnerability and the mechanisms involved in health disparities on an individual level, potentially leading to new targets for multi-level interventions that reduce the impact of cPSES on individuals disproportionally affected by obesity and cardiovascular disease.