Our Six Areas of Research Emphasis
The 81 researchers affiliated with the Center study a very broad range of topics related to ecogenetics and environmental health. For simplicity's sake we have assigned each member to one of six Areas of Research Emphasis or AREs. Many of our investigators work across 2 or more of these, but still identify primarily with their designated ARE.
Genomics of Xenobiotic Disposition
Mammals are equipped with an extraordinarily versatile system of metabolic enzymes and transport proteins that act on drugs and other xenobiotics, converting them either to benign, inactive metabolites, or transferring them across biological membranes against a concentration gradient and promoting net excretion from the body. A major emphasis of research from GXD investigators is focused on understanding the source of variability in biotransformation and transporter processes and how this defines individual susceptibility to the adverse effects of directly toxic or pro-toxic molecules. Factors that influence individual susceptibility to xenobiotic toxicity by modulating biotransformation or transporter activity include genetic determinants, previous exposure to enzyme/transporter inducing, inhibiting or activating substances, and tissue- and developmental-specific expression. (Core Leader: Dr. Evan Gallagher, UW DEOHS, email@example.com)
Environmental Mutagenesis & Carcinogenesis
Cancer continues to be a major health problem in the U.S, with an annual age-adjusted incidence rate of ~470 per 100,000 and an annual mortality rate of ~200 per 100,000 over the past decade. During 2010 it is estimated that more than 1.5 million persons in the US will develop the disease and over 560,000 will die as a consequence. Cancer develops through a complex multistage process in which cells change in ways that lead them to continuously multiply, increasing the likelihood of genetic mutations and eventually causing cancer. During each stage of this process, a number of genetic and environmental factors can influence whether the affected cells develop into cancer cells. Researchers are working to understand the environmental causes of human cancer, the underlying mechanisms by which these environmental causes act, and the genetic factors that help determine how an individual reacts to various environmental exposures. (Acting Core Leader: Dr. Christopher Kemp, Fred Hutchinson Cancer Research Center, firstname.lastname@example.org).
When it comes to environmental exposures and their effects on human health, some groups of people are more vulnerable to harm than others. Age, gender, health status, and genetics can all influence how likely an individual is to be harmed by any given exposure. Researchers associated with this Area of Research Emphasis focus on susceptible periods of development, which may include preconception impacts on fertility (reproductive toxicology), effects on early embryonic and fetal development (i.e., teratology), infant and childhood development, as well as the unique susceptibilities introduced by the process of aging. Investigators in the SSP ARE are interested in how environmental factors impact human development and reproduction and furthermore, how these impacts underlie developmental ontogeny of disease, and contribute to the onset of adult disease. Accordingly, investigators in this core use both in vitro and in vivo animal models as well as human epidemiology and clinical findings to identify potential gene-environment interactions of relevance. (Core Leader: Dr. Elaine Faustman, UW DEOHS, email@example.com)
Neurotoxicology & Neurodegenerative Disease
There is a continuous concern about the potential effects of neurotoxic chemicals, due in part to the lack of information on the overall magnitude of the problem of environmental neurotoxicity. Indeed, the number of people with neurotoxic disorders and the extent of neurologic disease and dysfunction that result from exposure to toxic chemicals in the environment are not known. Until a few years ago, only a few of the several thousand chemicals in commercial use had been tested for neurotoxicity, though the recent implementation of new guidelines for neurotoxicity and developmental neurotoxicity will, hopefully, help reduce these data gaps. Exposure to neurotoxic substances either in the workplace or through consumption of contaminated food has led to several outbreaks of neurotoxicity. Classical examples are the pesticides leptophos and kepone, triorthotolylphosphate, methylmercury and domoic acid. Occupational and/or environmental exposure to several chemicals such as solvents (e.g., toluene, styrene), metals (e.g., lead, manganese) and pesticides (e.g., organophosphates) are also associated with neurotoxic effects involving the central and/or peripheral nervous systems. Investigators in the neurotoxicology ARE are working in one or more of the following sub-areas: developmental neurotoxicity, role of neurotoxicants in neurodegenerative diseases, role of genetic polymorphisms in determining susceptibility to neurotoxicants, and cellular, biochemical and molecular mechanisms of neurotoxicity. (Core Leader: Dr. Lucio Costa, UW DEOHS, firstname.lastname@example.org)
Research Core focused on 'Respiratory Susceptibility' was established in the CEEH in the first application in 1995, with a primary focus on air pollution and asthma during the first 8 years. In 2003 the Core expanded its interest to include the area of environmental risk factors for cardiopulmonary and cardiovascular diseases, with Dr. Joel Kaufman as Director, and the Core also changed its name to reflect the direction of the research. The transition to an increased focus on atherosclerotic cardiovascular disease reflects the large public health impact of these disorders, and the increased understanding that modifiable environmental factors play a major role in risk. A very important issue in understanding cardiovascular toxicology remains that of identifying potential mechanisms of toxicity. For particulate matter air pollution this has remained a major challenge; despite relatively consistent epidemiologic studies, a compelling and coherent mechanism remains elusive. Several CVT investigators are exploring this, including the use of engineered susceptible animal models to explore mechanisms of cardiovascular toxicity. Several ongoing and proposed studies in the CVT ARE are actively pursuing projects that explore the roles of genetic susceptibility and gene expression in cardiovascular and pulmonary diseases to elucidate mechanisms in the entire population. (Core Leader: Dr. Michael Rosenfeld, UW DEOHS, email@example.com)
Proper characterization of human exposures is an essential component of epidemiologic studies and risk assessments, and provides biomedical researchers with information needed to develop realistic dosing studies. When considering gene-environment interactions, characterizing exposures is essential to quantifying the likely dose, and thus the estimation of such interactions. Results from exposure science studies are also vital for evaluating environmental justice concerns, and for developing interventions to prevent or minimize health hazards. This relatively new ARE draws upon the expertise and experience of the Exposure Sciences Program faculty within the Department of Environmental and Occupational Health Sciences, and includes two faculty members from Environmental Engineering and Biostatistics, both of whom have either adjunct or joint appointments in the department, as well as two from the School of Pharmacy. These faculty members have worked collaboratively with colleagues in several of the other CEEH cores to provide state-of-the-art methods in the use of biomarkers and other exposure assessment tools. (Core Leader: Dr. Mike Yost, UW DEOHS, firstname.lastname@example.org)