NIEHS Graduate Training Grant

Advanced Training in Environmental Toxicology

This training program aims to produce well-trained and versatile environmental toxicologists with doctoral degrees who will function as researchers, teachers and scientific managers in environmental health science. The scientific infrastructure is highly stimulating due to the presence of an NIEHS Center for Environmental Health Sciences, based in the Department of Environmental Toxicology, and the campus NIEHS Superfund Basic Research Program, to both of which many Training Grant faculty belong. Supported for a maximum of three years, trainees whose goals are compatible with this training program are selected by the Executive Committee by competition among applicants across the campus. Excellent academic preparation in chemistry, biochemistry and biology, research promise, and strong motivation toward a career in environmental health science are major criteria for selection.

Faculty List (†Director, *Executive Committee)

Anne Britt , Professor, Plant Biology, DBS – DNA repair, recombination, and damage tolerance mechanisms in higher plants

*Alan Buckpitt, Professor, Molecular Biosciences, Vet Med – Metabolic and biochemical mechanisms for lung-selective injury by environmental chemicals

Judith Charles, Assistant Professor, Environmental Toxicology, A&ES – Potentially toxic air pollutants, analysis of exposure to PCBs and other organochlorines

*Gary Cherr, Professor, Environmental Toxicology and Nutrition, A&ES – Mechanisms of reproductive and developmental toxicity in marine organisms and mice

Gino Cortopassi, Professor, Molecular Biosciences, Vet Med – Biochemistry, bioenergetics, molecular genetics, aging and toxicology of mitochondria

Michael DeGregorio, Professor, Hematology and Oncology, UCDMC – Pharmacology and metabolism of anti-cancer agents and SERMs focusing on breast cancer

Michael Denison, Professor, Environmental Toxicology, A&ES – Receptor-mediated mechanisms of action of environmental toxicants, especially halogenated aromatic hydrocarbons

Susan Ebeler, Professor, Viticulture and Enology, A&ES – Chemopreventive role of dietary polyphenols on tumor development

Bruce Hammock, Professor, Entomology, A&ES – Mechanisms of action and degradation of xenobiotics of natural and synthetic origin

Dallas Hyde, Professor, Anatomy, Physiology and Cell Biology, Vet Med – Lung-selective injury, especially the roles of chemokines and neutrophils

Carl Keen, Professor, Nutrition, A&ES – Developmental toxicity of environmental toxicants focusing on mineral metabolism and toxicant-nutrient interactions

Bill Lasley, Professor, Population Health and Reproduction, Vet Med – Endocrine aspects of female fertility and early pregnancy and applications to epidemiology

*Jerold Last, Professor, Pulmonary/Critical Care Medicine, School of Med – Mouse models of asthma and influence of air pollutants

Fumio Matsumura, Professor, Environmental Toxicology and Entomology, A&ES – Mechanisms of action of environmental pollutants, particularly pesticides and chlorinated organics

Kim McAllister, Assistant Professor, Neurology, School of Medicine -- Cellular and molecular mechanisms of synapse formation in the developing cerebral cortex

*Marion Miller, Professor, Environmental Toxicology, A&ES – Metabolism and protein targets of male reproductive toxicants, especially chlorinated compounds, nitroaromatics and herbicides

Alyson Mitchell, Assistant Professor, Food Science and Technology, A&ES – Biochemistry and toxicology of food chemicals such as flavonoids

Isaac Pessah, Professor, Molecular Biosciences, Vet Med – Mechanisms of calcium signal regulation and its perturbation by halogenated xenobiotics in neural development

Kent Pinkerton, Professor, Anatomy, Physiology and Cell Biology, Vet Med – Inhalation and respiratory toxicology, especially effects on lung growth, development and metabolism

Charles Plopper, Professor, Anatomy, Physiology and Cell Biology, Vet Med – Lung injury from environmental toxicants (ozone, nitrogen oxides, aromatics), tolerance and repair of the damage

†Robert Rice, Professor, Environmental Toxicology, A&ES – Differentiation of cultured human epidermal cells and its perturbation by metals (arsenic) and chlorinated aromatics (dioxin)

Henry Segall, Professor, Molecular Biosciences, Vet Med – Chemistry, metabolism, cytotoxicity and genotoxicity of pyrrolizidine alkaloids and other natural products

Taka Shibamoto, Professor, Environmental Toxicology, A&ES – Analysis of chemicals in food, including their roles in lipid peroxidation and their antioxidant activities

Ron Tjeerdema, Professor, Environmental Toxicology, A&ES – Fate and toxic actions of pesticides and petroleum products in aquatic organisms and systems

Barry Wilson, Professor, Animal Science and Environmental Toxicology, A&ES – Effects of excitotoxic chemicals (organophosphates) at molecular, cellular, tissue and whole animal levels

Dennis Wilson, Professor, Pathology, Microbiology and Immunology, Vet Med – Lung injury from circulating chemicals, role of metabolism and endothelial cell injury

Areas of Focus

Respiratory Toxicology (Buckpitt, Hyde, Last, Pinkerton, Plopper, D. Wilson).  Mechanisms of action and synergy of oxidants (ozone), combustion particulates (tobacco smoke), minerals and fibers (asbestos, silica), organics (naphthalene), natural products (monocrotaline); cloning and expression of lung cytochrome P450s and chemokines; acute and chronic cell injury from air pollutants and electrophilic metabolites; animal models (including monkey, transgenic and knockout mice) for pollutant effects on lung injury and repair, asthma, perinatal lung development, neutrophil interactions with airway epithelium, endothelial cell injury and pulmonary hypertension; identification of macromolecular targets by proteomic and genomic approaches.

Environmental and Metabolic Fate (Buckpitt, Charles, DeGregorio, Hammock, Miller, Segall, Tjeerdema).  Analysis of air pollutants, pesticides, petroleum hydrocarbons, and organochlorines (e.g., PCBs) in environmental samples by sensitive analytical methods such as mass spectrometry; development of sensitive high throughput techniques (using antibodies or specific chelators) to detect pesticides, metals and other environmental agents; metabolism of pharmaceuticals (anticancer agents including modulators of estrogen receptor activity) and natural products (pyrrolizidine alkaloids); examining role in toxic response of protein adducts of electrophilic metabolites of lung and male reproductive toxicants; cloning and expression of epoxide hydrolases and lung cytochrome P450s, characterization of their substrate specificities and comparative roles in toxic outcomes.

Developmental, Reproductive and Neurotoxicology (Cherr, Lasley, Miller, Pessah, B. Wilson).  Effects of multidrug resistance during embryogenesis on stage-specific and interspecies sensitivities; PAH effects on ߭catenin intracellular localization in sea urchins and mice; endocrine aspects of female fertility and early pregnancy in humans and monkeys; male reproductive toxicity from metabolites of benomyl, molinate, chlorinated hydrocarbons and nitroaromatics (1,3-dinitrobenzene); intracellular calcium signalling, perturbation by environmental chemicals (o-PCBs) in neurodevelopment; deleterious effects of excitotoxins (especially organophosphates) on target cell cultures and intact organisms.

Molecular and Cellular Targets (Britt, Cortopassi, Denison, Hammock, Matsumura, Rice).  Cellular responses to radiation-induced damage (cell cycle, DNA repair); role of mitochondrial DNA damage in apoptosis, deafness, neurodegenerative disease and other diseases of aging; molecular mechanism of action of Ah receptor ligands (including TCDD); development and application of high throughput bioassay for ligands of Ah and other cytosolic receptors; pathological actions of oxylipins (e.g., acute respiratory distress syndrome); mechanisms of signal transduction perturbation by chlorinated hydrocarbons and pesticides, including effects on ion channels, kinases, transcription factors and apoptosis; perturbation of keratinocyte growth and differentiation by TCDD, polycyclic aromatic hydrocarbons, oxidants, arsenic and other oxyanions (chromate, vanadate).

Food/Nutrition Toxicology (Ebeler, Keen, Mitchell, Shibamoto).  Analysis of food constituents (oxidants and other reactive compounds, pesticides) and their deleterious effects, including lipid peroxidation; role of anti-oxidants such as flavonoids and other polyphenols in biotransformation (e.g., glutathione S-transferase expression, protein adducts) and chemoprevention; influence of nutrition on developmental toxicity, especially toxicant-induced changes in mineral metabolism and epigenetic consequences of toxicant-nutrient interactions.