Systemic Toxicology

 

The broad goal of the Systemic Toxicology Research Program is to increase our understanding of health-related responses resulting from exposure to airborne environmental chemicals, the mechanisms underlying these effects, and the relationships between such effects and the pathogenesis of human disease. An important aspect of many studies within the Systemic Program is the evaluation of exposure factors that modulate biological responses. While high concentrations of toxicants in occupational settings are clearly associated with overt disease, the impacts of exposure to lower ambient concentrations in the exacerbation of preexisting disease states, or in the induction of new ones, is less clear. Many projects within the Program are, thus, characterized by the use of relatively low levels of exposure, so as to better model the ambient situation and avoid the need to extrapolate toxicology information from very high experimental exposure levels. A critical factor in our ability to develop experimental atmospheres appropriate to “real” human exposure situations is the availability of specific Facility Cores in the Department.

The research approaches within the Systemic Toxicology Program are quite broad, extending from exposure characterization to responses at the molecular, cellular, and whole animal levels. While most of our in vivo studies employ experimental animals, human exposure studies are also performed to better define the relationships between exposure to ambient and occupational air pollution and their health effects. The Program’s research has a particular emphasis on the physical and chemical components of exposure atmospheres and their specific influences on health-related indices, and we have developed technologies and procedures to characterize the temporal day-to-day variations in ambient aerosol composition over extended periods of time. One goal is to correlate such changes with the temporal variations in health-related responses being observed in epidemiology studies and in animals exposed to concentrated ambient particulate matter (CAPs).

The problems inherent in the characterization of environmental health effects are complex, and their study clearly requires interdisciplinary assessments. The ability to examine effects of pollutant chemical exposures at multiple investigatory levels and using both in vivo and in vitro exposure methodologies allows for the development of an integrated, mechanistic evaluation of toxicant action and disease pathogenesis. Almost all studies within the Systemic Toxicology Program are interdisciplinary in nature, and they cross traditional discipline boundaries both within this Program and between this Program and other Research Programs in the Department. This is clearly reflected by the extent of research collaborations within individual projects and is illustrated with jointly-authored publications. In particular, the Systemic Toxicology Program interacts extensively with Environmental Epidemiology researchers in cross-discipline studies that examine the role of individual components and sources of ambient particulate matter in adverse health effects. These collaborations examine air pollution-related health effects in the NYC metropolitan area as well as in urban centers throughout the U.S., Europe, and Asia.

While the focus of this Research Program is on pulmonary toxicology, current and recent research projects examine environmental influences related to air pollution exposures upon not only the respiratory, but also the immune, hepatic, nervous, and cardiovascular systems. Studies involving exposures via the respiratory system make up the largest component of the research portfolio. This has been a traditional focus of Systemic Toxicology at NYU, and is consistent with the long history of the Department of Environmental Medicine in the areas of inhalation toxicology and aerosol physiology, and its reputation for outstanding research accomplishments in the field of air pollution over the past 50 years.

Core Leadership

Dr. Terry Gordon, the Program Director for Systemic Toxicology, received a PhD from MIT in 1981. His research program focuses on areas: host susceptibility and particulate matter (PM). The lab utilizes both human and animal experimental models to study the genetic susceptibility underlying the adverse pulmonary and cardiac effects of environmental and occupational air pollutants. The key aim of the susceptibility work examines the contribution of age and genetic susceptibility to the adverse effects of inhaled pollutants. We examine the role of genetic host factors in murine models of disease using both classic mouse genetic and computational genomics approaches. Ongoing genetic studies examine the relative contribution of ozone, age, beryllium, hyperbaric oxygen, and nanoparticles to adverse effects. Because ambient PM produces significant adverse cardiopulmonary effects, our lab examines the role of coarse, fine, and ultrafine PM both in vitro and in vivo. We have collected ambient PM in several cities in the U.S., Germany, and China (the latter both during and after the 2008 Olympics) and ongoing studies focus on the differential toxicity of PM on the basis of particle size, season, composition, and urban/rural location.