Humans receive significant ambient daily exposures to multiple environmental contaminants, including by-products of combustion (polycyclic aromatic hydrocarbons) and plastics (phthalates and organotins). The goal of these studies is to determine the molecular mechanisms by which individual and complex mixtures of contaminants impair the development and function of the mammalian immune system. The immune system requires ongoing development in the face of constant pathogen exposures throughout life. The bone marrow is a multifunctional organ that supports life-long B lymphocyte development, along with bone homeostasis, and these two functions are interconnected. Research in laboratories of Drs. Sherr and Schlezinger have demonstrated that B cells developing in the bone marrow are highly susceptible to contaminant-induced apoptosis. These laboratories continue to examine mechanisms contributing to activation of cell death, with a particular focus on how interaction with nuclear receptors (Dr. Sherr: aryl hydrocarbon receptor and Dr. Schlezinger: peroxisome proliferator activated receptor g (PPARg)) contributes to contaminant-induced effects. A novel direction of this research also addresses the hypothesis that contaminant-induced alterations in bone development and the bone marrow microenvironment contribute to suppression of lymphopoiesis. Further, as real-world exposures typically involve complex chemical mixtures, the Schlezinger laboratory investigates how chemicals within the mixtures may interact to enhance deleterious effects. Understanding these pathways is important because loss of B lymphocytes could potentially impair the ability to mount an immune response to infections. On the other side of the coin, understanding of death pathways and mixture interactions potentially may be put to use in the development of new chemotherapeutics.
Faculty involved in this research are: