| Program Faculty
The University of Minnesota encourages transdisciplinary cooperation in graduate education. Thus, a member of the faculty who has a primary academic appointment in one department may be a member of the graduate faculty of another unit, with full faculty privileges. There are 15 preceptors in this training program Ten preceptors hold primary appointments in the Division of Environmental Health, but several hold primary appointments in other academic units within the Academic Health Center. These are Dr. Hanna, Medicinal Chemistry, Drs. Holtzman and Sparber, Pharmacology; Dr. Hecht, Lab Medicine and Pathology, and Dr. Thompson, Epidemiology. All preceptors are, however, members of the Graduate Faculty in Environmental Health, and participate actively in training graduate students in Environmental Health. Preceptors are in one of four specialty tracks. These include Toxicology, Epidemiology, Exposure Assessment, and Policy. All preceptors have funded research programs and are active members of the Environmental Health Graduate program. The research interests of each preceptor are described briefly (beginning with the program director, and co-director then arranged alphabetically).
William A. Toscano, Jr., Ph.D.: Research focuses on environmental signals and sensors (ecotransanology). The goal is to develop a detailed understanding of the actions of chemicals in the environment that disrupt cellular signal and information systems, and their impact on human health. We study receptor-mediated toxicity, with particular interest in the mechanism of dioxin action. Recent work has focused on interactions of the dioxin receptor and intracellular receptors that modulate growth, differentiation, and development. Studies on transgenic in situ sensors of dioxins in the environment are ongoing. Another newresearch theme is the study Ah receptor action on hox genes during zebrafish development.
Lisa A. Peterson, Ph.D.: Research focuses on genotoxic and nongenotoxic mechanisms by which chemicals initiate cancer. The projects apply organic, biological and analytical chemical methods to this problem. Dr. Peterson is interested in the events occurring after DNA alkylation that contribute to the carcinogenic properties of chemicals. One project in the laboratory explores the interaction between two different DNA alkylation pathways derived from one parent carcinogenic compound. She has been investigating this question with the tobacco-specific nitrosamine, 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK). NNK is a lung-specific carcinogen and likely contributes to human lung cancer induced by the use of tobacco products. Another project in her laboratory investigates the mechanism by which a nongenotoxic carcinogen, furan, induces liver tumors. A third project explores the modulation of mitogen-activated protein kinase pathways (MAPKs) by genotoxic alkylating agents. The central hypothesis is that activation of MAPKs by genotoxic agents aids in the fixation of mutations and the clonal expansion of initiated cells. Trainees will participate in these research projects by designing and performing experiments.
John Adgate, Ph.D.: Research interests focus on understanding the role of science, especially the exposure assessment process, in environmental decision-making and improving the assessment, management, and communication of environmental health risks. He has published papers on lead poisoning prevention, indoor air pollution, pesticide exposure assessment, and the use of risk assessment in environmental health policy. His current research focuses on: 1) children's multi-pathway exposures to pesticides; 2) personal exposure to airborne particulate matter, transition metals, and volatile organic chemicals; and 3) improved methods for lead poisoning prevention.
Bruce H. Alexander, Ph.D.: Research interests are in applied occupational and environmental epidemiology and epidemiologic methods. Current research includes occupational exposure to fluorochemicals and cancer mortality; pesticide exposure assessment in farm families; determinants of agriculture related injuries in children; occupational and environmental determinants of prostate cancer and the molecular epidemiology of prostate cancer; cancer risks associated with long-term low dose ionizing radiation exposure. Other research interests include effects of occupational exposures on fertility and pregnancy abnormalities, epidemiologic methods for studying environmental influences on reproductive health, and the use of biological markers in epidemiologic research.
Timothy R. Church, Ph.D.: Research interests are in mass screening for cancer and other chronic diseases; clinical trial and case-control methods; methods for estimating screening test performance; and identification and treatment of cardiac arrhythmia with implantable devices. He is currently conducting the Colon Cancer Control Study, the Prostate, Lung, Ovarian, and Prostate cancer screening trial, the pilot study for the National Colonoscopy Trial, the Case-control Study for Risk Factors in Prostate Cancer, two trials chemo-prevention of polyps, and the Wright County Study of Fecal Occult Blood-Screening. He also collaborates on the School-based Study of Complex Environmental Exposures, the Nurses' Assault Study, the Risk of Injury Study II, and the Farm Family Exposure Study.
Patrick Hanna, Ph.D.: Research focuses on the role N-Acetyltransferases play in metabolic detoxification and bioactivation of a diverse group of drugs, carcinogens, and environmentally important chemicals. Acetylation is a major metabolic pathway for hydrazines, hydrazides and arylamines. N-Acetyltransferases also catalyzes the conversion of carcinogenic arylhydroxylamines and arylhydroxamic acids to reactive metabolites which form covalent adducts with proteins and DNA. One research objective is to gain insight into differences in the substrate specificities and active site topologies of N-acetyltransferase isozymes by identifying critical peptide and amino acid residues and elucidating their contributions to substrate binding and catalysis. A second major objective is to identify and characterize the arylamine-protein adducts formed because of N-acetyltransferase-catalyzed bioactivation of carcinogens. The results of the research will provide a basis for understanding the functions and catalytic mechanisms of N-acetyltransferases and will contribute to defining the chemical mechanisms through which the bioactivated carcinogens form adducts with their macromolecular targets.
Stephen S. Hecht, Ph.D.: Research in the Hecht laboratory focuses on carcinogens that occur in tobacco products and the diet. The carcinogens being investigated are N-nitrosamines and polycyclic aromatic hydrocarbons. We carry out chemically oriented studies to understand mechanisms of metabolic activation and detoxication of these compounds, and to determine the structures of DNA adducts that they form. These investigations are performed in vitro and in vivo in laboratory animals. The goal is to understand fundamental mechanisms involved in DNA adduct formation and initiation of tumorigenesis by these compounds. We apply the knowledge gained from the above studies to develop methods to detect biomarkers, including metabolites, protein adducts, and DNA adducts in humans who may have been exposed to these compounds, or in whom endogenous formation is expected.
Jordan L. Holtzman, M.D., Ph.D.: Areas of research interest related to toxicology include investigation of the activation of drugs and environmental compounds by the cytochrome P450 system to form toxic metabolites, and the role of oxidant damage in cell toxicity. Thee focus is on the role of the thiol:protein disulfide oxidoreductases in the repair of protein damage secondary to oxidant stress. Currently the role of apoptosis in the initiation of cell death by menadione in a lymphoblast cell line is under investigation.
George Maldonado, Ph.D.: Dr. Maldonado is a methodologist with a Ph.D. in Epidemiology, extensive training and experience in Biostatistics, and a special interest in methods for quantifying all sources of error in health studies. He has published a number of articles on the topic of validity, primarily in the areas of confounding and specification bias--most of these in collaboration with Dr. Sander Greenland, an internationally recognized expert in the validity of health studies. Currently he is principal investigator on a five-year methodological study funded by NIH. The objective of this study is to develop formal methods for evaluating the magnitude of bias in environmental epidemiology studies, so that uncertainty about the role of bias will be minimized. More specifically, he is developing methods for evaluating bias using sensitivity analysis, a technique that can be used to examine how the magnitude of bias varies under different scenarios.
Gurumurthy Ramachandran, Ph.D.: Areas of interest include occupational and ambient exposure assessment, Bayesian methods in retrospective exposure assessment, inhalation dosimetry for mixed exposures, aerosol measurements, theoretical and experimental studies on design of aerosol samplers, and inversion methodology). Dr. Ramachandran is part of a collaborative study with Dr. E. V. Wattenberg focusing on the toxicology of metal mixtures on cultured lung cells.
Leslie L. Robison, Ph.D.: Research is focused on topics directly relating to pediatric cancer. He is actively involved in a number of analytic epidemiologic studies designed to identify risks associated with specific forms of childhood cancer; with the study of acute leukemia being a particular interest. In addition, he has an active research program directed toward the long-term health effects resulting from cancer treatment among survivors of childhood cancer. This research includes outcomes such as second malignancies, late mortality, fertility and offspring, cardiac and pulmonary complications and health-related behaviors.
Sheldon B. Sparber, Ph.D.: Research focuses on neurotoxicology and behavioral toxicology is the mainstay of this laboratory. Effects of organo heavy metals upon neurochemical and behavioral function, including measures of learning and memory, has been the focus of a program designed to study both the toxicology of this class of agents, as well as their utility as tools for inducing models of neuropathological and/or age-related cognitive dysfunction. Additionally, they have been used successfully to "unmask" subtle neurodevelopmental effects of other insults to specific areas of the CNS or generally. The second major thrust of this laboratory is the study of neurobehavioral toxicology associated with drugs of abuse, withdrawal from them, and the mechanisms for long-term consequences of exposure during development. These include stressors, such as hypoxia/hypercapnia, undernutrition and early-experience behavioral factors, which result from exposure to the agent itself or withdrawal from it, as in severe neonatal or in utero withdrawal. Studies include effects upon the CNS, endocrine, cardiovascular and immune system.
Deborah Swackhamer, Ph.D.: Dr. Swackhamer studies the behavior and fate of persistent organic pollutants, and the exposures to these chemicals. Her research includes the study of bioaccumulation of persistent organics in fish and aquatic foodwebs, pollutant dynamics in the Great Lakes, and the identification and effects of endocrine disrupting chemicals in water and wastewater. She is Director of the Midwest Ecological Risk Assessment Center (MERAC), which coordinates research on ecological risks among faculty at the University, and helps provide research expertise in this area to the state regulatory agencies.
Elizabeth V. Wattenberg, Ph.D.: Research focuses on the molecular mechanisms of chemical carcinogenesis. Most recently, the research in my laboratory has focused on mechanisms by which non-genotoxic carcinogenic agents, classified as tumor promoters, modulate carcinogenesis through their interaction with mitogen-activated protein kinase signaling pathways. Tumor promotion is one of the longest phases in carcinogenesis, and is potentially reversible. Therefore, understanding the molecular mechanisms of tumor promotion is critical for developing methods to prevent and treat cancer. Classic EPA risk assessment methods have largely ignored the contribution of environmental tumor promoters to carcinogenesis. Understanding the molecular mechanisms of tumor promotion is critical for refining cancer risk assessment methods.
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