We investigate how the innate immune system is affected after exposure to environmental pollutants during and after differentiation. During an infection, Dendritic cells and Macrophages acquire defined identities culminating in the generation of an orchestrated immune response. This process is a precise temporal regulation of genes that program developmental decisions as well as the function of antigen presenting cells to regulate T cell differentiation for instance. Of the many factors that influence the function of the cells of the innate immune system, cytokines and chemokines are important regulators in a fine-tuned immune response. Activation of receptors and transcription factors such as Toll like receptors (TLR) and NF-kB is believed to be critical to orchestrating key molecular events in the transcriptional regulation of genes controlling a classical immune response. More recently the physiological role of the Aryl hydrocarbon receptor (AhR), a receptor protein for environmental chemicals and dietary components, has been identified as a transcriptional regulator of lymphoid cell subsets critical to mucosal immunity for instance. We believe that activation of AhR by toxic ligands and the resulting disturbance of TLR and NF-kB signaling pathways are the origin of deregulated immune response mechanisms leading to the devastating consequences of immune disorders.
Research in pulmonary toxicology is facilitated by the unique inhalation facilities that are available to Center for Health and the Environment investigators. These facilities include chambers for study of the health effects of environmental tobacco smoke. Research projects include investigations of the adverse effects of smoke on lung development and immunofunction, as well as on pathogenesis and chemoprevention of lung cancer. Other research projects focus on the adverse health effects of ozone inhalation. The emphasis of pulmonary epidemiology studies is on the hazards of agricultural dusts and chemicals to farmworker health.
The research activities in reproductive toxicology complement and build upon the program in molecular toxicology, and these projects have focused on the interactions between steroid hormones and xenobiotics in the mechanisms of toxicity to reproductive tract cells. Research in genetic toxicology is focused on the heritable effects of paternal irradiation and the mechanisms by which these effects are transmitted through the germ line. Activities in reproductive epidemiology involve the development and clinical validation of biomarkers for population-based studies of female and male reproductive health. These biomarkers are being applied in large-scale epidemiologic studies of the effects of ethnic background, lifestyle factors and environmental agents on reproductive function.
Research in epidemiology and preventive medicine is focused primarily on the agricultural workplace. Farmers, farmworkers and their children are being studied to evaluate the relationships between exposure to pesticides and other agricultural chemicals and adverse outcomes including cancer and neurobehavioral effects. New biomarkers of pesticide exposure are also being developed.
Research in comparative toxicology and wildlife health is facilitated by the unique animal and clinical research facilities which are available to Center for Health and the Environment investigators. These facilities include specialized animal research areas for birds and fish. Clinical research facilities include a survival surgery, recovery room and dedicated necropsy room. Species under investigation in field studies and/or laboratory experiments include non-human primates, terestrial and marine mammals, birds, fish and amphibians. Investigations focus on animal behavior, prevention and treatment of environmental exposures and population control.
Aquatic toxicology includes acute and chronic toxicology regarding individual and population health effects of environmental contaminants on native and non-native invertebrate fish and shellfish populations. Biomarker approaches include development toxicology, histopathology, enzyme-, and immuno-histochemistry of aquatic organisms.
Research in this area is focused on environmental and biological analytical chemistry. This includes plant, invertebrate and fish biochemistry and ecotoxicology, biogeochemistry of pollutants and natural products.