Curriculum in Toxicology

www.med.unc.edu/toxicology

JAMES A. SWENBERG, Director

Professors

Louise M. Ball, Metabolism and Genotoxicity of Environmental Xenobiotics

Thomas W. Bouldin, Neuropathology, Ocular Pathology and Neurotoxicology

Kim R. Brouwer, Pharmacokinetics, Hepatic Transport, Hepatobiliary Disposition, Biliary Excretion, Hepatotoxicity

Stephen G. Chaney, DNA Repair and Platinum Anticancer Drugs

Frank C. Church, Thrombosis and Hemostasis, Breast and Prostate Carcinogenesis, Macromolecular Structure-Function

Rosalind A. Coleman, Diabetes, Obesity, Regulation of Triacylglycerol Synthesis, Glycogen Storage Disease

William B. Coleman, Hepatocarcinogenesis, Tumor Suppressor Genes, Biology of Liver Stem Cells, Cancer Epigenetics

Marila Cordeiro-Stone, DNA Repair and Replication in Human Cells, Mechanisms of Response to DNA Damage

Fulton T. Crews, Neurodegeneration and Chronic Drug-Induced Changes in Brain Signaling Pathways

Channing J. Der, Ras Protein Superfamily, Signal Transduction and Oncogenesis

Marilie D. Gammon, Cancer Epidemiology

Avram Gold, Structure-Reactivity Relationships in Metabolism and Mutagenicity of Polycyclic Aromatic Hydrocarbons

Milan J. Hazucha, Health Effects of Air Pollutants, Human Studies, Mechanisms of Response

David J. Holbrook Jr., Biochemical Toxicology, Xenobiotic Metabolism

David G. Kaufman, DNA Replication, Chemical Carcinogenesis

William K. Kaufmann, DNA Metabolism in Radiation and Chemical Carcinogenesis

Jean M. Lauder, Developmental Neurobiology, Developmental Biology, Neurotoxicology

Nobuyo N. Maeda, Animal Models of Hyperlipidemia, Atherosclerosis and Cardiomyopathy

Terry Magnuson, Mammalian Genetics, Genomics and Development

Richard B. Mailman, Neurotoxicology and Neuropharmacology of the Nervous System

Patricia F. Maness, Axon Guidance and Signal Transduction in Nervous System Development

Robert C. Millikan, Cancer, Genetic and Molecular Epidemiology

A. Leslie Morrow, Neurotoxicology and Excitotoxicity of Alcohol

Leena A. Nylander-French, Development of Methods to Monitor and Assess Dermal Exposure to Chemical Carcinogens and Contact Sensitizers

Andrew F. Olshan, Molecular Epidemiology of Cancer, Reproductive and Developmental Outcomes

Winston Campbell (Cam) Patterson, Vascular Biology, Angiogenesis, Protein Folding and Degradation

David B. Peden, Translational and Clinical Research in Environmental Lung Disease

Gary M. Pollack, Pharmacokinetics and Pharmacodynamics of Therapeutic and Toxic Agents

Daniel Pomp, Genetic Architecture of Complex Traits, Gene-Environment Interactions, Polygenic Mouse Models, Obesity

Bryan L. Roth, Cardiopulmonary Toxicology, Research Translation, Animal Models of Human Diseases, Biomarkers

Marschall S. Runge, Cardiopulmonary Toxicology, Vascular Biology, Thrombosis and Atherosclerosis, Role of Reactive Oxygen Species

R. Jude Samulski, Development of Efficient Viral Vectors for Gene Delivery into Eukaryotic Genes

Aziz Sancar, DNA Repair and Cancer, Structure and Function of DNA Repair Enzymes, Human Blue-Light Photoreceptor

Kathleen K. Sulik, Developmental Toxicology, Embryology

James A. Swenberg, Carcinogenesis, DNA and Protein Adducts, Cell Proliferation, Risk Assessment

Alexander Tropsha, Molecular Modeling, Computer-Assisted Drug Design, Molecular Dynamics of Proteins, Protein Folding

Terry A. Van Dyke, Genetically Engineered Mice, Cancer Models, Roles of p53, pRb and PTEN

Paul B. Watkins, Mechanistic Toxicology, Hepatotoxicology, Research Translation, Biomarkers

Bernard E. Weissman, Chromatin Remodeling and Epigenetic Alterations in Human Cancer

Elizabeth M. Wilson, Environmental Androgens and Antiandrogens, Androgen Receptor Regulation of Prostate Cancer

Steven H. Zeisel, Nutrients and Brain Development, Choline and Carcinogenesis, Isoflavones and Cancer, Antioxidants and Apoptosis

Associate Professors

Lisa A. Carey, Breast Carcinogenesis, Research Translation, Animal Models of Human Diseases, Biomarkers

Mohanish P. Deshmukh, Molecular Mechanisms of Apoptosis in Neurons and Other Postmitotic Cells

Lee M. Graves, Protein Kinases and Cell Signaling, Regulation of Cell Metabolism and Toxicity

Ilona Jaspers, Cellular Mechanisms of Air Pollutant Toxicity

Jeffrey M. Macdonald, Metabolomics and Fluxomics Using NMR Spectroscopy and Imaging, Tissue Engineering

Charles M. Perou, Characterization and Classification of Human Breast Tumors into Subtypes of Biological and Clinical Importance

Dale A. Ramsden, V(D)J Recombination and DNA Double Strand Break Repair

Scott H. Randell, Identification of Airway Epithelial Stem Cells, Airway Innate Immunity, Pathophysiology of Lung Diseases

Robert A. Roubey, Developmental and Immunotoxicology, Animal Models of Human Diseases, Biomarkers

Ivan I. Rusyn, Environmental Genomics

Philip C. Smith, Toxicokinetics and Xenobiotic Metabolism, Peptide Analysis and Disposition

Nancy E. Thomas, Molecular Carcinogenesis, Environmental Toxicology, Molecular Epidemiology, Research Translation, Biomarkers

David W. Threadgill, Mammalian Genetics, Systems Genetics, Toxicogenomics, Gene-Environment Interactions, Cancer Susceptibility

Assistant Professors

David Neil Hayes, Lung Carcinogenesis, Research Translation, Biomarkers, Computational Toxicology

Mary F. Paine, Drug Xenobiotic Metabolism, Pharmacokinetics, Drug Xenobiotic Interactions

W. Kimryn Rathmell, Genetics of Renal Cell Carcinoma

Norman E. Sharpless, Tumor Suppressor Genes, Genetics of Cancer and Aging

Research Associate Professor

Miroslav Styblo, Metabolism and Biological Effects of Essential and Toxic Metals and Metalloids

Adjunct Professors

Melvin E. Andersen, Pharmacokinetic and Pharmacodynamic Modeling of Environmental Compounds

Trevor Archer, Molecular Carcinogenesis, Chromatin Structure, Control of Gene Transcription, Epigenetics

Linda S. Birnbaum, Chemical Disposition of Xenobiotics, Mechanistic Toxicology, Dose-Response and Risk Assessment

John A. Cidlowski, Apoptosis, Steroids, Glucocorticoid Receptors, Hormone Action, Nucleases, Gene Regulation

Daniel L. Costa, Cardiopulmonary and Inhalation Toxicology, Health Effects of Air Pollutants

Robert B. Devlin, Pulmonary Toxicology, Molecular Biology

David C. Dorman, Experimental Neurotoxicology, Nasal Toxicology, Pharmacokinetics

Steven R. Kleeberger, Genetic Determinants of Environmental Lung Disease

Ronald P. Mason, Free-Radical Intermediates in the Metabolism of Toxic Chemicals

Stephanie Padilla, Behavioral Toxicology and Neurotoxicology

John M. Rogers, Developmental Toxicology, Teratology, Developmental Biology, Embryology, Nutrition

MaryJane K. Selgrade, Immunotoxicology

Robert C. Sills, Molecular Pathology

Hugh A. Tilson Jr., Behavioral Toxicology, Developmental Neurotoxicology

Michael D. Waters, Mutagenesis and Carcinogenesis, Toxicogenomics

Adjunct Associate Professors

James W. Allen, Genetic Toxicology, Toxicogenomics and Epigenetic Mechanisms in Chemical Carcinogenesis

Kevin M. Crofton, Understanding the Consequences of Endocrine Disruption on Neurodevelopment

Michael DeVito, Development of Models for Cumulative Risk to Endocrine Disruptors

David Díaz-Sánchez, Translation Research, Environmental Impacts on Human Health, Immunology, Genetic susceptibility, Epigenetics

Suzanne Fenton, Environmental Effects on Mammary Gland Development and Function

M. Ian Gilmour, Experimental Toxicology

G. Jean Harry, Developmental Neurotoxicology, Molecular Neuro/Immunotoxicology

E. Sidney Hunter, Mechanisms of Developmental Toxicity, Oxidative Stress, Embryonic Stem Cells in Developmental Toxicity

Urmila P. Kodavanti, Cardiovascular Diseases and Susceptibility, Air Pollutants, Cardiopulmonary Interactions, Molecular mechanisms, Genetic and Environmental Factors

Edward L. LeCluyse, Cellular/Molecular Mechanisms Regulating Liver Cytochrome P450 Enzymes Expression

Michael C. Madden, Air Pollution Toxicology, Lung Oxidative Stress and Inflammation

Ram (T. V.) Ramabhadran, Neurotoxicological Effects of Environmental Pollutants, Cellular Stress Pathways

James M. Samet, Inflammatory Responses to Pollutant Inhalation, Cytokines, Eicosanoids

Kenneth R. Tindall, Molecular Mutagenesis, Somatic Cell Mutation, Role of Mutagenesis in Carcinogenesis

Gregory S. Travlos, Hematology and Clinical Chemistry

Nigel Walker, Risk Assessment, Receptor-Mediated Toxicants, Environmental Contaminants and Mechanisms of Carcinogenesis

Douglas C. Wolf, Chemical Carcinogenesis

Adjunct Assistant Professors

Ronald E. Cannon, Cancer Biology, Transgenic Mouse Models

Michael G. Narotsky, Developmental Toxicology, Pregnancy Maintenance and Parturition

The Curriculum

The Curriculum in Toxicology administers a degree program leading to the award of the Ph.D. in toxicology. The curriculum is an interdisciplinary program, and its faculty is drawn from various administrative units of the Schools of Medicine, Pharmacy and Public Health. The training faculty also includes scientists at government laboratories on campus or in the Research Triangle Park (e.g., EPA, NIEHS). The research interests of the faculty include most areas of toxicology, with particular emphasis on understanding the links between the environment and health risks, the mode of action of toxicants and disease pathogenesis and how emerging knowledge could be translated into prevention strategies, new therapeutic interventions and an improved scientific basis for risk assessment. The main areas of research concentration are molecular carcinogenesis, mechanistic toxicology, neurotoxicology, cardiopulmonary toxicology, hepatic toxicology, computational toxicology, developmental toxicology, immunotoxicology, drug and xenobiotic metabolism and ethanol toxicology. Multidisciplinary efforts are directed at environmental toxicology, systems biology, animal models of human diseases, translational research and biomarkers. The faculty generally does not conduct research in the areas of aquatic toxicology, forensic toxicology, the ecological aspects of toxicology or studies in invertebrate systems. The research activities of the Curriculum in Toxicology are conducted in the laboratory facilities assigned to each faculty member by a participating administrative unit.

Applications

Students with interest in the Ph.D. degree in toxicology must apply for Graduate School admission through the Biological and Biomedical Sciences Program. Applications are considered from students who have received or expect to receive a B.S./B.A. or an M.S. degree in a scientific discipline. A desirable background for predoctoral studies in toxicology includes courses in biological sciences (including histology and animal physiology), in chemistry (including analytical and organic) and mathematics through calculus, although all of these are not absolutely essential. A strong course in general biochemistry accelerates the student's progress. Applicants are evaluated on the basis of undergraduate (and graduate) academic performance, Graduate Record Examination (GRE) scores and letters of recommendation. Students are accepted on the basis of their achievement and potential. Prior research experience is strongly considered in the assessment of qualifications for admission.

Requirements for the Ph.D. Degree

The selection of graduate courses is influenced by the student's prior academic background. The academic courses that we consider appropriate for graduate training in toxicology include biochemistry, biostatistics, pathology, pharmacology, toxicology and two or three elective courses in the specific areas of the doctoral research. In addition, each predoctoral student is expected to participate in a minimum of 12 credit hours of nondidactic training activities; i.e., two semesters of laboratory experience (research rotations) prior to selection of the doctoral research project and four semesters of student-centered seminars. Attendance and participation in the Curriculum in Toxicology seminar series is also required.

A major requirement for the Ph.D. degree is a doctoral dissertation based on the student's independent laboratory research. Written and oral examinations are required in the fields of general toxicology and the major research interest.

Financial Aid

The curriculum seeks to fund predoctoral students each year. All applicants are considered for financial aid awards.

Courses for Graduates and Advanced Undergraduates

423 [123] DEVELOPMENTAL TOXICOLOGY AND TERATOLOGY (CBIO 423) (2). Emphasis is placed on topics of current research interest relative to the genesis of environmentally caused and genetically based birth defects. One two-hour session per week . Spring. (2009 and alternate years.) Cell and Developmental Biology and Toxicology faculty: Sulik, Rogers, and Hunter (course directors).

442 [142] BIOCHEMICAL AND MOLECULAR TOXICOLOGY (BIOC 442, ENVR 442) (3). Prerequisites, any combination of two courses in biochemistry, molecular biology, cell biology or cell physiology (or permission of the course director). Development of a comprehensive understanding of biochemical and molecular actions of environmental chemicals and toxicants, and proper application of novel laboratory techniques for hypothesis-driven mechanistic research. Three lecture hours per week. Spring. Toxicology faculty: Rusyn (course director).

Courses for Graduates

702 [202] PRINCIPLES OF PHARMACOLOGY AND TOXICOLOGY (PHCO 702) (3). Prerequisite, PHCO 701 or approval of the instructor. Introduces the major areas of pharmacology and toxicology and serves as a basis for more advanced courses. Three lecture hours per week. Spring. Pharmacology faculty: Johnson (course director).

707 [207] ADVANCED TOXICOLOGY (PHCO 707, ENVR 707) (3). Prerequisite, PHCO 702 or permission of the course director. Cellular and physiological basis of toxicity of environmental chemicals, with emphasis on inhalation toxicology, developmental toxicology, immunotoxicology, radiation toxicology, renal toxicology and neurotoxicology. Three lecture hours per week. Fall. Toxicology faculty: Swenberg (course director).

715 [215] INTRODUCTION TO TOXICOLOGICAL RESEARCH (4). Introductory laboratory experience from research projects of limited scope to acquaint students with the experimental approaches, techniques and equipment of current research in toxicology. May be repeated. Twelve laboratory hours per week. Fall, spring and summer. Toxicology faculty: Nylander-French (course director).

720 [220] TOXICOLOGY SEMINAR I (1). Seminar series to introduce recent advances, methodology and terminology in toxicology. One hour per week. Fall and spring. Toxicology faculty: Padilla (course director).

721 [221] TOXICOLOGY SEMINAR II (1). Student-conducted presentations and discussions of recent advances in toxicology; emphasis on critical evaluation of published investigations and on organization and oral delivery of presentations. May be repeated up to three times. One hour per week. Fall and spring. Toxicology faculty: Padilla (course director).

722 [222] TOXICOLOGY SEMINAR III (ENVR 722) (1). Presentations by outside invited speakers, local faculty, advanced graduate students and postdoctoral trainees. Topics will cover all areas of research in toxicology. One hour per week. Fall and spring. Toxicology faculty: Rusyn (course director).

750 [250] APPLIED BIOSTATISTICS (PATH 750, PHCO 750, CBIO 750) (1). Data analysis for biomedical scientists. This largely self-study course deals with basic statistical and quantitative methods for the analysis and interpretation of biomedical data. This course is required for PHCO/TOXC/PATH graduate students. Permission of the instructor is required for other students. Fall. Graves (course director).

760 [260] TOXICOKINETICS (3). A quantitative examination of the time course of absorption, distribution, metabolism, excretion and biologic effects of agents of toxicologic interest. Three lecture hours per week. Fall. (2009 and alternate years.) Brouwer, Paine (course codirectors).

792 [292] SEMINAR IN CARCINOGENESIS (PATH 792) (2). Prerequisite, permission of the course director. Survey of classical and current literature on selected critical issues in carcinogenesis. Discussions consider experimental methods and observations as well as theories and generalizations. Two seminar hours per week. Spring. Pathology faculty: Coleman (course director).

901 [301] RESEARCH IN TOXICOLOGY (Var.). May be repeated for credit. Hours and credits to be arranged. Fall, spring and summer. Toxicology faculty.

993 [393] MASTER'S THESIS (Var.). May be repeated. Hours and credits to be arranged. Fall, spring and summer. Toxicology faculty.

994 [394] DOCTORAL DISSERTATION (Var.). May be repeated. Hours and credits to be arranged. Fall, spring and summer. Toxicology faculty.