The Division of Intramural Research
National Institute of Environmental Health Sciences
Overview
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| The Division of Intramural ResearchNational Institute of Environmental Health Sciences |
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Overview
The National Institute of Environmental Health Sciences, as part of the National Institutes of Health, is dedicated to reducing the burden of diseases and dysfunctions associated with the environment. This mission is accomplished by conducting basic and applied research into the effects of environmental exposures on biological systems and human health, on the identification of susceptible human subpopulations, and on the interaction between the environment, genetics, and age. Through a multidisciplinary biomedical research program, disease prevention and intervention efforts, and communication and education programs, the Institute strives to make a significant contribution to human health.
The Institute fulfills its mission through three main channels:
DIR scientists are highly interactive and are often engaged in interdisciplinary research. This encourages efficient testing of novel ideas, innovative hypotheses, and new paradigms. DIR scientists are also actively involved in translational research. New advances in cell and molecular biology are being extended not only into molecular medicine (from bench to bedside) but also into disease prevention (from bench to longer, healthier lives). Translational research must take advantage of new advances in designing interventions for disease prevention as well as disease treatment.
In sum, DIR scientists are involved in research that contributes to our basic understanding of biological and chemical processes, to our understanding of the role of environmental agents in human disease and dysfunction, and to the underlying mechanisms of environmentally associated diseases. The DIR is organized into three programs: environmental biology, environmental toxicology, and environmental disease and medicine. Each program has a director, who is responsible for assisting and advising the Scientific Director in the overall scientific leadership of the DIR. The organizational structure and personnel of the three programs are presented in the following pages.
This program (Dr. Thomas A. Kunkel, Scientific Program Director) is involved primarily with basic research in the areas of genetics, signal transduction, and structural biology, as is reflected in the titles of its three component Laboratories, the Laboratory of Molecular Genetics, the Laboratory of Signal Transduction, and the Laboratory of Structural Biology.
Laboratory of Molecular Genetics
http://dir.niehs.nih.gov/dirlmg/
Environmentally associated diseases are often of mutational origin. The Laboratory of Molecular Genetics (Dr. John W. Drake, Chief) studies the basic mechanisms of the mutational process, fundamental mechanisms of genomic stability, and the impact of environmental agents on the genetic apparatus. The Laboratory also examines mutational processes relevant to diseases initiated by microbial infections. There are eight research groups in this Laboratory, which are listed below with the Group Leader and areas of study.
Mitochondrial Replication: Dr. William C. Copeland (copelan1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/B_Copeland.html
Mechanism, regulation and initiation of mammalian mitochondrial DNA replication;
role of mtDNA polymerases in mitochondrial pathologies.
Bacteriophage T4: Dr. John W. Drake (drake@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/J_Drake.html
Genetic and enzymological determinants of rates of spontaneous mutation and DNA repair in bacteriophage T4; regularities in magnitudes of spontaneous mutation in all organisms.
DNA Replication Fidelity: Dr. Thomas A. Kunkel (kunkel@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/T_Kunkel.html
DNA replication fidelity; eukaryotic DNA mismatch repair; DNA polymerase structure/function relationships; molecular mechanisms of mutagenesis.
Drosophila Chromosome Structure: Dr. James M. Mason (masonj@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/J_Mason.html
Mutator mutations; cell cycle control in DNA repair; consequences of telomere loss; telomere structure.
Chromosome Stability: Dr. Michael A. Resnick (resnick@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/M_Resnick.html
Ectopic recombination, homologous recombination and chromosomal mutations; mammalian DNA cloning and stability; isolation of human
genes by functional class.
Mechanisms of Mutation: Dr. Roel M. Schaaper (schaaper@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/R_Schaaper.html
Mutator and antimutator mutations, DNA mismatch repair, endogenous DNA damage, spontaneous mutation, DNA replication fidelity.
DNA Repair and Mitochondrial Injury: Dr. Bennett Van Houten (vanhout1@niehs.nih.gov)
Structure-function studies, and protein-DNA interactions involved in damage recognition and repair; formation, repair and consequences of mitochondrial DNA damage.
Recombination Mismatch Repair: Dr. Leroy Worth (worth@niiehs.nih.gov)
http://dir.niehs.nih.gov/dirlmg/L_Worth.html
Mechanistic aspects of DNA Mismatch Repair in genome stability: Role(s) in controlling the level of homologous recombination.
Laboratory of Signal Transduction
http://dir.niehs.nih.gov/dirlst/
Environmental agents can affect physiological processes and cause pathological outcomes by disrupting signal transduction pathways. Major areas of emphasis in the Laboratory of Signal Transduction (Dr. John Cidlowski, Chief) include mechanisms of actions of steroid and orphan receptors; cell surface neurotransmitter receptors; mechanisms of regulation of calcium, tyrosine kinase and inositol signaling; and of ion channels. A major effort is involved in elucidating the mechanisms and regulation of apoptosis. The Laboratory's various research groups, group heads, and areas of study are listed below:
Membrane Signaling: Dr. David L. Armstrong (armstro3@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/armstrong.htm
Ion channel regulation by G protein signal transduction pathways.
Polypeptide Hormone Action: Dr. Perry Blackshear (black009@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/blackshear.html
Mechanisms of signal transduction in response to peptide hormones and cytokines; signal transduction in development.
Molecular Endocrinology: (Dr. John Cidlowski) (cidlows1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/cidlowski.htm
Mechanisms and control of apoptosis; glucocorticord receptors; orphan receptors.
Tyrosine Kinase Signaling and Regulation: Dr. John P. O'Bryan (obryan@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/obryan.htm
Role of adaptor proteins in tyrosine kinase signaling; mechanisms of growth transformation, differentiation and development.
Calcium Signaling: Dr. James W. Putney, Jr. (putney@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/putney.htm
Cellular calcium regulation; neurotransmitter utilization of calcium.
Inositol Signaling: Dr. Stephen B. Shears (shears@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/shears.htm
Roles of Inositol polyphosphates as regulators of cellular physiology.
Ion Channel Physiology: Dr. Jerrel L. Yakel (yakel@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlst/yakel.htm
The role of neuronal nicotinic receptors in neuronal signaling.
Cell Biology: Dr. Elizabeth Murphy (murphy1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Signaling pathways involved in apoptosis, mechanisms responsible for cell protection; alterations in ionic homeostasis in response to cell stress.
Laboratory of Structural Biology
http://dir.niehs.nih.gov/dirlsb/
The mission of the Laboratory of Structural Biology (Dr. Thomas A. Kunkel, Chief) is to provide insights into biological processes that modulate the effects of environmental exposures on human health. To accomplish this, the laboratory investigates the relationship between the atomic level structures of macromolecules and their biochemical properties, their abilities to interact with substrates and other molecules including those of environmental concern, and their functions in vivo. This requires an integrated approach wherein x-ray crystallography, nuclear magnetic resonance, mass spectrometry and computational chemistry are combined with biochemical and genetic approaches.
Computational Chemistry/Molecular Modeling: Dr. Thomas A. Darden (darden@niehs. nih.gov) and Dr. Lee Pedersen (pedersen@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlsb/cchome.htm
Research into methodological issues in molecular dynamics simulations; use of classical and quantum chemical techniques in macromolecular structure- function investigations.
Macromolecular Structure: Dr. Traci M. T. Hall (hall4@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlsb/hall_home.html
Structural studies of macromolecules involved in embryonic development, mRNA stability, and protein-facilitated RNA catalysis, primarily using x-ray crystallographic techniques.
Nuclear Magnetic Resonance: Dr. Robert London (london@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlsb/nmrhome.htm
Application of NMR to biological problems; analysis of ligand-macromolecule interactions using transferred NOE and inter-ligand Overhauser effects; analysis of macromolecular structure using NMR spectroscopy, development of intracellular indicators for metal ions, xenobiotic metabolism; NMR support service for other Intramural researchers.
Mass Spectrometry: Dr. Kenneth Tomer (tomer@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlsb/msshome.htm
Development and application of mass spectrometric techniques to biological problems, including protein characterization, proteomics, posttranslational modifications and receptor-ligand interactions; epitope mapping of HIV-related proteins, analyte identification and quantification; mass spectrometry support service for other Intramural researchers.
Nucleic Acid Enzymology: Dr. Samuel H. Wilson (wilson5@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlsb/naehome.htm
Biochemical, biophysical, and structural characterization of proteins involved in nucleic acid transactions, especially base excision repair processes. This includes structure-function studies of DNA polymerases, especially DNA polymerase b and HIV-1 reverse transcriptase.
A number of diseases and dysfunctions have known or suspected environmental components in their etiologies. Special emphasis in the Environmental Diseases and Medicine Program (Dr. Kenneth Korach, Scientific Program Director) is placed on cancer, reproductive and developmental dysfunction, and pulmonary diseases. The Program is also concerned with the planning and conduct of epidemiological and clinical studies, the development of animal models and the maintenance of the Institute's laboratory animal facilities, and the conduct of biostatistical research and support to DIR basic and applied studies. The Environmental Diseases and Medicine Program consists of the Epidemiology Branch, the Laboratories of Reproductive and Developmental Toxicology, Pulmonary Pathobiology, Molecular Carcinogenesis, Womens Health, the Comparative Medicine Branch, and the Biostatistics Branch.
Epidemiology Branch
http://dir.niehs.nih.gov/direb/
The Epidemiology Branch (Dr. Allen J. Wilcox, Chief) studies the impact of environmental factors on human health. While the presence of chemical contaminants and other toxicants in the environment are a potential threat to health, the extent of this threat remains unclear. There are several aspects that make environmental effects on health difficult to demonstrate. In the past, environmental research has often relied on the crudest, most easily measured health effects (cancer or death), while more subtle damage (e.g. infertility, disruption of immune function, endocrine imbalance) may be a more common result of such exposures. Environmental toxicants are often at low concentrations, and illness may not emerge until years after exposure. Also, any given toxicant might produce more than one type of health problem depending on timing and dose, individual susceptibility and other factors.
We have adopted multiple strategies to address these problems. Our approaches include (1) improvements in exposure measurement, (2) identification of genetically susceptible subgroups, (3) detection of disease in its early stages, and (4) the study of illnesses for which causes are largely unknown but environmental causes are plausible. Examples include uterine fibroids and autoimmune diseases. Some of our most important tools come from recent developments in biotechnology. New laboratory assays can document low-dose exposures, early disease expression, and genetic susceptibility in ways that were not possible even a few years ago.
The Branch is divided into two Sections. One studies chronic disease and the other focuses on reproduction.
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Environmental and Molecular Epidemiology: Dr. Dale P. Sandler, Chief (sandler@niehs.nih.gov); Drs. Jack A. Taylor (taylor@niehs.nih.gov);
Stephanie J. London (london@niehs.nih.gov); Matthew P. Longnecker (longnec1@niehs. nih. gov); Glinda S. Cooper (cooper1@niehs.nih.gov);
Freja Kamel (kamel@niehs.nih.gov)
Agricultural pesticides (neurologic, reproductive, and renal dysfunction); organochlorines (breast cancer); radon (lung cancer, childhood cancer) and electromagnetic fields (breast cancer); lead exposure (amyotrophic lateral sclerosis); osteoporosis; auto-immune and other immune-related diseases;
exposure-specific mutation in critical target genes (lung and bladder cancer); leukemia; gene-environment interaction.
Reproductive Epidemiology: Dr. Allen J. Wilcox, Chief (wilcox@niehs.nih.gov);
Drs. Donna D. Baird (baird@niehs.nih.gov); Ruth E. Little (little1@niehs.nih.gov); Andrew S. Rowland (rowland@niehs.nih.gov); Walter J. Rogan (rogan@niehs.nih.gov)
Pregnancy loss and the biology of reproduction; uterine fibroids; lead, cadmium (pre-eclampsia and oxidative damage); fathers' occupational exposures (pregnancy outcome); industrial/agricultural pollution in the Ukraine (preterm delivery, fetal growth, infertility); genetic and occupational factors (cleft lip and palate); lead exposures in children; attention deficit/hyperactivity disorder
Laboratory of Reproductive and Developmental Toxicology
http://dir.niehs.nih.gov/dirlrdt/
The research goal of the Laboratory of Reproductive and Developmental Toxicology (Dr. Kenneth S. Korach, Chief) is to understand basic mechanisms underlying normal and abnormal development and reproduction. The research in development includes studies of germ cell differentiation, genital tract development, ontogeny of hormone response, and development and regulation of gene expression. Reproductive studies seek to understand the molecular control and biological function of steroid receptor proteins and metabolizing enzymes, germ cell biology, and the functional cell biology of estrogens and other hormonal agents. The diversity of scientific disciplines represented in these studies establishes the Laboratory as a unique resource within the NIH. As members of a component laboratory of the NIH, scientists in the Laboratory of Reproductive and Development Toxicology recognize the human health implications of their basic research and how it may contribute to public health efforts and clinical investigations. Organizationally, the Laboratory consists of the following groups:
Chromatin and Gene Expression: Dr. Trevor K. Archer (archer1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Chromatin
Chromatin structure, steroid hormone activation of transcription, nuclear receptor mediated chromatin remodeling, transcriptional co-activator and co-repressor proteins, histone acetylation and phosphorylation, macromolecular chromatin remodeling complexes.
Gamete Biology: Dr. E. Mitch Eddy (eddy@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Gamete
Male reproduction, regulation of gene expression during spermatogenesis, development of germ cells; gene targeting.
Receptor Biology: Dr. Kenneth S. Korach (korach@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Receptor
Mechanisms of estrogen hormone action, hormonal carcinogenesis; bone biology; reproductive biology; receptor signal coupling.
Molecular Development Biology: Dr. Yuji Mishina (mishina@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Molecular
Mouse embryology, developmental genetics, function of growth factor signaling pathways, pattern formation during embryogenesis, neural induction, embryonic stem cell (ES cell) technologies; tissue-specific gene targeting.
Pharmacogenetics: Dr. Masahiko Negishi (negishi@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Pharm
Regulation of liver enzymes; sex-dependent gene imprinting of gene expression; structural and functional analyses of drug-metabolizing enzymes.
Gene Regulation: Dr. Christina Teng (teng@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Gene
Molecular mechanisms of steroid hormone action, expression of estrogen regulated genes, chromatin structure, hormone responsiveness.
Orphan Receptor: Dr. Cary Weinberger (weinber1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlrdt/home.htm#Orphan
Identification of orphan receptors and associated ligands; hormone receptors;
gene regulation.
Laboratory of Pulmonary Pathobiology
http://dir.niehs.nih.gov/dirlpp/
The respiratory tract is a target for a broad spectrum of air pollutants. These pollutants can cause acute or chronic damage to various tissue compartments and compromise their functions including the defenses against airborne microbial pathogens, thus rendering the host susceptible to respiratory tract infections. Examples of such toxic air contaminants include acid aerosols, silica particles and asbestos fibers, reactive gases (e.g., aldehydes, ozone, and nitrous oxides), tobacco smoke and diesel engine exhaust. These agents can cause or exacerbate major diseases of the conducting airways including asthma, bronchitis, bronchogenic carcinoma, or diseases of the pulmonary parenchyma such as pneumonitis, fibrosis and emphysema. To design effective strategies for disease prevention and interaction, we need to improve our knowledge of the biology of the respiratory tract system. The primary concern of the Laboratory of Pulmonary Pathobiology (Dr. Anton Jetten, Acting Chief) is to broaden our knowledge of respiratory tract system biology at the cellular, biochemical and molecular level, and to develop a better understanding of pathogenic mechanisms involved in the onset of diseases of the airways. The Laboratory pursues this broadened understanding through the following research groups and areas of study:
Airway Inflammation: Dr. James C. Bonner (bonnerj@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpp/#inflamm
Fibroproliferative lung disease, environmental airway pollutant particles; fibroblast and airway smooth muscle cell hyperplasia; growth factor receptor alterations.
Cell Biology: Dr. Anton M. Jetten (jetten@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpp/#cell
Regulation of differentiation and gene expression and control of irreversible
growth arrest in epidermal, mammary and lung epithelial cells; function of nuclear receptors.
Clinical Studies: Dr. Darryl Zeldin (zeldin@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpp/#clinical
Eicosanoid biochemistry, role of eicosanoids in lung function; regulation and functional significance of cytochrome P450 enzymes that metabolize fatty acids; mechanisms of lung injury and repair; allergen-induced airway inflammation, primary prevention of asthma.
Laboratory of Molecular Carcinogenesis
http://dir.niehs.nih.gov/dirlmc/
The research efforts of the Laboratory of Molecular Carcinogenesis (Dr. Thomas Eling, Acting Chief) are designed to elucidate the mechanisms of environmental carcinogenesis by identifying the target genes in this process and by defining how chemicals act upon these genes to influence cancer development. The Laboratory is particularly interested in hormonally related cancers, including breast cancer, endometrial cancer, ovarian cancer, and prostate cancer. Efforts to clone new genes involved in these cancers as well as genes involved in growth processes, such as cellular senescence and apoptosis, are being actively pursued. The mechanisms by which tumor suppressor cells and oncogenes function in the growth and metastasis of human and rodent cancers are also addressed. Studies on mechanisms by which prostaglandin H synthase and lipoxygenases can lead to tumor development and the development of chemopreventive agents. The major research groups and areas of specific study within the Laboratory are as follows:
Molecular Toxicology: Theodora R. Devereux (devereux@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Mouse liver and lung carcinogenesis, beta-catenin mutations, Wnt signalling, gene expression changes, lung tumor susceptibility, nongenotoxic carcinogens, oxidative stress.
Hormones and Cancer: Dr. Richard DiAugustine (diaugus2@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Determination of growth factor signaling pathways in the mammary gland and
uterus stimulated by the ovarian steroid estradiol or progesterone; identification
of activated receptor tyrosine kinases and their substrates in breast and uterine carcinomas.
Eicosanoid Biochemistry: Dr. Thomas Eling (eling@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Role of cyclo-oxygenase and lipoxygenase in modulation of growth factor signaling pathways, breast cancer, colon cancer, apoptosis, and cellular proliferation. Studies on the mechanisms responsible for inhibition of tumor development by prostaglandin synthase (COX) inhibitors.
Regulatory Protein: Dr. B. Alex Merrick (merrick@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Expression, regulation, and translocation of regulatory proteins (e.g., p53, p21, and PCNA); polyaromatic hydrocarbons.
Metastasis: Dr. Kenneth Olden and Dr. John D. Roberts (roberts1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Cell adhesion and invasion, integrins, fibronectin, extracellular matrix, tumor cell metastasis, adhesion-mediated signal transduction.
Molecular and Genetic Epidemiology: Dr. Jack Taylor (Joint appointment in the Epidemiology Branch) (taylor@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm and http://dir.niehs.nih.gov/direb/taylor.htm
Molecular epidemiology, gene-environment interaction, DNA repair, polymorphism, mutagenesis, bladder cancer, lung cancer, prostate cancer, epatocellular carcinoma.
Cell Adhesion and Migration: Dr. Steven Akiyama (akiyama@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Integrin, fibronectin, extracellular matrix, tumor cell biology, cell adhesion, cell migration, basement membrane, monoclonal antibodies, metastasis.
Gene Regulation: Dr. Cynthia A. Afshari (afshari@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlmc/c.htm
Main area of emphasis is in investigation of how signaling pathways directed
toward negative regulation of cell growth are impacted by compounds such as
non-mutagenic carcinogens. Studies are focused on the G1 checkpoint, BRCA1, senescence genes, and transcriptional regulation events.
Cancer and Aging: Dr. J. Carl Barrett (Adjunct Appointment) (barrett@mail.nih.gov) Cellular senescence; apoptosis; genetic instability; prostate cancer; breast cancer.
Laboratory of Women's Health
The Laboratory of Women's Health (Dr. Barbara J. Davis, Chief) focuses on important diseases in women, such as breast cancer, ovarian cancer, uterine leiomyoma, ovarian dysfunction, and pregnancy and parturition dysfunctions. The Laboratory studies how these diseases develop and occur over the life span of a woman and how environmental toxins and stresses cause these diseases. The ultimate goal is to reduce the burden of environmentally related diseases. The Laboratory has initiated a clinical study, the Uterine Leiomyoma Longitudinal Intervention Study (ULLIS) designed to define the growth dynamics of uterine leiomyomas through time and develop markers for growing and/or clinically relevant leiomyomas that will be important in future studies of the etiology, therapy, and prevention of these tumors. LWH also is developing genetically defined animal models that provide links between molecular medicine, human epidemiology and experimental studies. These models provide opportunities to identify key genes and signaling mechanisms of the reproductive systems that interact with the environment over time at different stages of life. The overall goal is to integrate genetics, endocrinology, immunology, pathology, epidemiology, and clinical research to study diseases in women in order to discover new ways to prevent environmentally related diseases.
Female Reproductive Pathology: Dr. Barbara J. Davis (davis1@niehs.nih.gov)
Provides pathological evaluation and conducts mechanistically based research to complement NTP female reproductive toxicity studies; investigates role of potential endocrine disrupters on female reproductive toxicity in vivo and in vitro,
the latter being based on rodent and human granulosa cell cultures.
Comparative Carcinogenesis: Dr. Roger W. Wiseman (wiseman@niehs.nih.gov)
Breast/ovarian cancer susceptibility genes (BRCA1 and BRCA2), mouse models for BRCA defects; Cre/LoxP conditional gene targeting.
Biostatistics Branch
http://dir.niehs.nih.gov/dirbb/
Investigators in the Biostatistics Branch (Dr. Clarice Weinberg, Chief) are concerned with research in biomathematics and population genetics, with the design and analysis of laboratory animal toxicology and carcinogenicity studies, and with the development of methodology for epidemiological and clinical studies. In addition, they provide computational and statistical support to Institute scientists. Within the Statistics and Biomathematics Branch there are three main areas of study.
Laboratory Studies: Drs. Joseph Haseman (haseman@niehs.nih.gov);
Gregg Dinse (dinse@niehs.nih.gov); Beth Gladen (gladen@niehs.nih.gov);
David Dunson (dunson@niehs.nih.gov); Shyamal Peddada (peddada@niehs.nih.gov)
Analysis of tumor incidence data; body weight/tumor incidence correlations;
historical control data; false positive/false negative rates; experimental design
and data analyses.
Human Studies: Drs. Clarice Weinberg (weinberg@niehs.nih.gov); Beth Gladen (gladen@niehs.nih.gov); David Umbach (umbach@niehs.nih.gov); David Dunson (dunson@niehs.nih.gov)
Reproduction and fertility; effects of radon, PCBs and DDE; gene-environment interactions; measurement errors.
Biomathematics and Population Genetics: Dr. Norman Kaplan (kaplan@niehs.nih.gov)
Locating disease genes using linked markers; permutation based methods in population genetics; theoretical population genetics models.
Comparative Medicine Branch
http://dir.niehs.nih.gov/dircmb/
The Comparative Medicine Branch (Dr. Diane B. Forsythe, Chief; Dr. Mary Grant, Deputy Chief) provides a broad range of services and collaborative support for the NIEHS Intramural research programs including animal facilities management, animal procurement, health surveillance and disease diagnosis, clinical veterinary services, rodent breeding, technical and surgical assistance, quality assurance support, Animal Care and Use Committee support, and provide professional advice on important animal issues. Its main organizational components and their areas of focus are listed below.
Animal Resources: Dr. Mary Grant, Acting Section Chief (goelz@niehs.nih.gov)
http://dir.niehs.nih.gov/dircmb/
Procures all animals used in intramural research; provides daily husbandry
and animal care to research animals housed in NIEHS facilities; manages more than 30 rodent breeding colonies including transgenic mice, producing over 20,000 rodents annually that are not commercially available; maintains four flexible film isolators that house gnotobiotic rats and mice for use in research and as sentinel monitors in the disease surveillance program; provides technical assistance in dosing, blood collection, weight determinations, food consumption, clinical observations, survival procedures, tissue collection, pathological examination, vaginal cytology and estrus cycle determination for intramural research programs.
Veterinary Medicine: Dr. Terry Blankenship-Paris (blaken1@niehs.nih.gov)
http://dir.niehs.nih.gov/dircmb/
Provides clinical veterinary support; full animal diagnostic services including pathological examination; assistance with Animal Study Proposal review; polyclonal antibody production; support and refinement of surgical, technical,
and anesthetic techniques; transgenic survival support including capsule implantations, ovarian transplantations, ovariectomies, and cesarean sections.
Quality Assurance: Dr. Julius E. Thigpen (thigpen@niehs.nih.gov)
http://dir.niehs.nih.gov/dircmb/
Provides animal health surveillance; testing of animal feed, water and bedding; monitors equipment and animal environment to determine effectiveness of sanitation and sterilization procedures; provides pest control program; works with Veterinary Medicine Section to maintain the disease-free status of the Institute animal colonies and to prevent the introduction of potential diseases; evaluates tissue/cell lines for the presence of contaminants.
As was indicated previously, the NIEHS plays a major leadership role in helping the National Toxicology Program (NTP) achieve its overall goals. While many of the research programs within the Intramural Division contribute to the achievement of the NTP goals, the primary effort in support of the NTP is contained within the Environmental Toxicology Program (ETP). The ETP houses what is generally regarded as one of the foremost classical toxicology laboratories in the world. In addition, ETP staff collaborate closely with scientists from the Environmental Biology and the Environmental Diseases and Medicine Programs to bridge the gap between classical toxicology and modern molecular biology and to form a research interaction that is, perhaps, unique in the environmental health sciences.
The ETP (Dr. Christopher J. Portier, Acting Director; Dr. John Bucher, Deputy Director) is responsible for: (1) providing toxicological evaluation on substances of public health concern; (2) developing and validating improved methods (more sensitive, specific and rapid); (3) developing approaches and generating data to strengthen the science base for risk assessments; and (4) communicating with all stakeholders. The ETP achieves its program goals by a combination of independent investigator-initiated research, program-related research and testing, and contract testing and support activities.
The ETP is made up of the Office of the Program Director and four research/service Laboratories, which are the Laboratory of Computational Biology and Risk Analysis, the Laboratory of Toxicology, the Laboratory of Pharmacology and Chemistry, and the Laboratory of Experimental Pathology. Additional administrative support for the Program is provided by the Toxicology Operations Branch and the Offices of NTP Liaison and Scientific Review, Special Programs, and Risk Assessment.
Laboratory of Computational Biology and Risk Assessment
http://dir.niehs.nih.gov/dirlcbra/
The Laboratory of Computational Biology and Risk Assessment (Dr. Christopher J. Portier, Chief) has five primary responsibilities: (1) conducting and coordinating research into the development and use of mechanistic data and models for characterizing and quantifying human health risks associated with exposure to environmental agents; (2) maintaining an active research program in computer-based mathematical modeling, ranging from efforts at the cellular and molecular levels to whole animals and focused on describing and evaluating chemical structures, biological response mechanisms and their perturbations by potentially hazardous environmental agents; (3) developing and using cellular and molecular markers to investigate the link between environmental exposures and toxicity; (4) providing approaches for evaluating human susceptibility factors that modulate toxicity to environmental agents; and (5) studying the interaction of opioid receptors with endogenous and synthetic ligands. The diverse, but highly interactive, research efforts of the Laboratory are organized into the following units:
Genetic Risk: Dr. Douglas A. Bell (bell1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlcbra/generisk.htm
Testing the hypothesis that human genetic differences in carcinogen
metabolism and DNA repair influence the risk of DNA damage, mutation and
cancer. Developing methods for gene expression profiling in order to
identify disease susceptibility genes.
Peptide Neurochemistry: Dr. Lawrence H. Lazarus (lazarus@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlcbra/peptide.htm
Development of new opioidmimetic peptides; structure-activity relationships of opioid peptides; molecular dynamics conformation of opioid analogues and opioid receptor; molecular biology of opioid receptors.
Statistical Modeling and Risk Assessment: Dr. Christopher J. Portier (portier@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlcbra/statmodel.htm
Development of qualitative and quantitative methodology for risk assessment; application of risk assessment methodology to novel compounds; predictive linking of biochemical models to stochastic models; development of theoretical models for noncancer endpoints.
Toxicokinetic Modeling: Dr. Ronald Melnick (melnickr@niehs.nih.gov) and Dr. Christopher Portier (portier@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlcbra/pbmod.htm
Enhancing physiologically-based toxicokinetic modeling through the incorporation
of more anatomical and biochemical realism; modeling the distribution, metabolism and clearance of environmental agents; developing new models for genetic effects of environmental toxicants; assessing the ability of models to predict across species; providing support to the NTP.
Laboratory of Toxicology
http://dir.niehs.nih.gov/dirlt/
The Laboratory of Toxicology (Dr. Michael D. Shelby, Chief) has five major roles:
(1) designs, directs and conducts studies to characterize chemical toxicity including system/organ-specific effects such as immune, reproductive, genetic, respiratory and nervous system toxicities; (2) studies the interactions of chemicals and metabolites with subcellular macromolecules; (3) plans and conducts research to update and improve methods for characterizing toxicity of chemicals and other agents; (4) coordinates Laboratory activities with those of other intramural and extramural scientists to develop mechanistic data relevant to toxicological issues of scientific/public health significance; and (5) interacts with other research and regulatory agencies regarding toxicological evaluations of agents of public health concern. The Laboratory is organized into the following units:
Alternative Systems: Dr. James G. Burkhart (burkhart@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/burkhart.htm
Comparison/correlation of alternative/natural environmental species and laboratory animal models; transgenic fish models; role of alternative test systems in human risk assessment.
Environmental Immunology: Dr. Dori Germolec (germolec@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/germolec.htm
Identification and investigation of adverse effects on the immune system resulting from exposure to environmental agents; assessment of the cellular
and molecular roles of cytokines in organ toxicity, including such target sites as the skin, lung and liver.
Neurotoxicology: Dr. G. Jean Harry (Harry@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/harry.htm
Chemical-induced alterations in neuron-glia interactions; brain injury and the cytokine inflammatory response; early alterations in neural cells prior to neuronal loss; differential susceptibility of developing cell types.
Mammalian Mutagenesis: Dr. Heinrich V. Malling (malling@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/malling.htm
Investigation of spontaneous and chemical-induced mutations in somatic and, particularly, germ cells; mutation assessment based on the Am54 transgenic
mouse model that uses a PHIX174 viral transgene; evaluation of point mutations at an AT base pair that affects the host range of the recovered bacterophage.
Respiratory Toxicology: Dr. Daniel L. Morgan (morgand@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/morgan.htm
Characterization of toxic effects of inhaled environmental chemicals; animal models
of pulmonary disease; metabolic and pharmacokinetic information on inhaled chemicals; maintenance and operation of inhalation exposure facilities used by toxicology research groups throughout the Institute.
Developmental Endocrinology Studies: Retha R. Newbold (newbold1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlt/newbold.htm
Development of an animal model that has replicated and predicted adverse
effects of DES in prenatally-exposed humans; mechanisms of endocrine disrupting chemicals; dose response relationships; role of estrogens in normal/abnormal development.
Laboratory of Pharmacology and Chemistry
http://dir.niehs.nih.gov/dirlpc/
The Laboratory of Pharmacology and Chemistry (Dr. John Pritchard, Chief), utilizing the approaches and techniques of pharmacology, biochemistry, molecular biology, and chemistry (1) studies the processes of exposure and disposition of environmental chemicals; (2) studies the enzyme systems involved in metabolism of environmental chemicals and drugs including their genetic heterogeneity; (3) studies the mechanisms responsible for the toxic effects of xenobiotics and their metabolites including photochemical and free radical mechanisms; (4) provides a focus within NIEHS for the application of alternative model systems from comparative and marine biology to study the pharmacology and toxicology of chemicals and drugs; and (5) provides chemistry support for the NTP and the DIR, including the assessment of chemical purity, stability, and biotransformation. The organizational structure of the Laboratory consists of the following groups:
Photochemistry/Photobiology: Dr. Colin F. Chignell (chignell@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Investigates the mechanisms of photosensitization; examines the role of photochemical activation of xenobiotics with respect to their toxicity.
Metabolism and Exposure Markers: Dr. Burhan Ghanayem (ghanayem@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Uses a biochemical approach to identify chemical and biological markers for xenobiotic exposure; correlates exposure and metabolism to specific toxic effects and their mechanisms.
Human Metabolism: Dr. Joyce Goldstein (goldste1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Studies genetic polymorphisms of human cytochrome P450s; discovery of new polymorphisms, expression of recombinant P450s and their mutants in a cDNA expression system, development of genetic tests, and assessment of the functional consequences of the genetic variations both in vitro and in vivo in clinical populations. Studies of the physiological function of the CYP2Cs in humans and a murine model.
Keywords, human CYP enzymes, polymorphisms, drug metabolism, CYP2C subfamily, CYP2C8, CYP2C19, CYP2C9, clinical drugs.
Neuropharmacology: Dr. Jau-Shyong Hong (hong3@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Long-term consequences of altering gene expression in the nervous system; study of the molecular mechanisms underlying the regulation of opioid peptides; elucidation of the roles of opioid peptides in the modulation of physiological processes or pathological conditions such as neurodegenerative diseases.
Free Radical Metabolites: Dr. Ronald P. Mason (mason4@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Utilization of electron spin resonance and spin trapping methods to identify the participation of radical-mediated toxicity in the effects of organic xenobiotics and heavy metals; investigation of the mechanisms responsible for radical-mediated toxicity.
Chemistry: Dr. Leo T. Burka (burka@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Provides toxicological characterization of chemicals for the DIR and NTP through research and direction of contracts primarily in the areas of analytical and bioanalytical chemistry. Research is primarily in the areas of chemical metabolism, disposition,
toxicokinetics, and chemical toxicity.
Chemical Metabolism and Toxicokinetics: Dr. Leo T. Burka (burka@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Investigates the mechanisms of chemical toxicity using biochemic pharmacology and pharmacokinetics; directs contract resources for studies of chemical disposition.
Chemistry Resources: Dr. Cynthia S. Smith (smith19@nieish.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Provides chemistry expertise and advice for the DIR and NTP scientists; conducts studies requiring characterization, quantitation, dose formulation, fate
and bioanalysis of chemicals under investigation by NTP and DIR through
contracted chemistry resources.
Intracellular Regulation: Dr. David S. Miller (miller@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Utilizes confocal microscopy and quantitative image analysis to investigate both cell surface and intracellular events responsible for elimination of foreign chemicals and drugs by liver, kidney and blood-brain barrier, with particular emphasis on cellular control of these processes.
Renal Pharmacology: Dr. John Pritchard (pritcha3@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Examination of the pharmacology of renal xenobiotic elimination, including membrane transport mechanisms, molecular biology of transporters, and membrane-mediated toxicity. Transport of xenobiotics and drugs across barrier epithelia, e.g., choroid plexus, is also studied.
Inorganic Carcinogenesis: Dr. Michael P. Waalkes (waalkes@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlpc/
Heavy metal carcinogenesis.
Laboratory of Experimental Pathology
http://dir.niehs.nih.gov/dirlep/
The Laboratory of Experimental Pathology (Dr. Robert Maronpot, Chief) (1) conducts research on spontaneous and chemically induced pathologic lesions and the mechanisms by which they are induced; (2) develops and defines in vivo and in vitro models of experimental carcinogenesis and toxicology; (3) develops new methods and technologies in pathobiology; (4) manages, evaluates, reviews, and reports all pathology data generated through the conduct of the NTP toxicology and carcinogenicity studies; (5) establishes standards, terminology, and diagnostic criteria for rodent pathology; (6) maintains the NTP Archives and provides laboratory animal medicine support for the NTP; (7) maintains state-of-the-science histology, electron microscopy, and clinical pathology laboratories; and (8) provides diagnostic pathology support to all NIEHS investigators and the NIEHS laboratory animal colony. The Laboratory is organized into the following research groups and areas of support or study:
Comparative Pathobiology: Dr. Darlene Dixon (dixon@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/compath.htm
Studies the role of growth factors (e.g., TGFa, IGF-I, VEGF) and their receptors in murine and human uterine leiomyomas ("fibroids"; myomas) and leiomyosarcomas; Using in vitro models, investigates the role of environmental and endogenous factors potentially modulating the growth and development of uterine smooth muscle tumors in rodents and women.
Bioassay and Technical Reports: Dr. James R. Hailey (hailey@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/biotech.html
Provides various levels of participation, oversight, and communication of pathology-related issues at all stages of two-year rodent toxicology/
carcinogenesis studies; responsible for NTP pathology peer review; provides in house pathology support for investigators using conventional and genetically engineered rodents.
Pathology Support: Dr. Ronald A. Herbert (hebert@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/pathsup.html
Operates histology and electronmicroscopy core laboratory that supports in
house investigators as well as the NTP.
Clinical Pathology: Dr. Gregory S. Travlos (travlos@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/clinpath.html
Provides hematology, clinical chemistry, and hormone analysis for Institute investigators and in support of NTP; provides interpretation of clinical pathology data generated in NTP contracted studies.
Molecular Pathology: Dr. Robert C. Sills (sills@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/molpath.html
Investigates mechanisms of toxicity and carcinogenicity in support of the NTP bioassay studies; emphasis is on genetic alterations in rodent cancers and cancer/toxicity studies involving Clean Air Act chemicals.
Laboratory Animal Management: Dr. Ghanta Rao (rao@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/labman.html
Provides laboratory animal management support to the NTP and NIEHS toxicological testing and research programs, including establishing and maintaining production colonies, disease monitoring, compliance with laboratory animal care and quality control of feed and bedding. Research activities include toxicologic evaluation of AIDS therapeutics and dietary intervention to prevent/delay mammary cancer in transgenic animal models.
Special Techniques: Ms. Julie Foley (foley1@niehs.nih.gov)
http://dir.niehs.nih.gov/dirlep/groups/spectech.html
This core support laboratory provides technical advice, expertise, and methods development in support of NIEHS investigators and the NTP; techniques and
areas of support include image analysis, laser capture microdissection, immunohistochemistry, tissue array, and ultracryomicrotomy.
The Laboratory of Environmental Carcinogenesis and Mutagenesis (Dr. Raymond Tennant, Chief) focuses on chemical, physical, and environmental causes of cancer and on utilizing transgenic animals and intelligent computer models to distinguish carcinogens and the mechanisms by which they act. The goals of the Laboratory are: (1) to understand the role of specific gene mutations and epigenetic events in cancer development; (2) to understand the role of exogenous and endogenous chemicals and other environmental factors in the induction of cancer; (3) to derive insights into the relationships between mutagenicity, chemical structure, and mechanisms of mutagenesis and carcinogenesis; and (4) to reduce risk to human health by improving the ability to rapidly identify, classify, or quantify the effects of potential mutagens and carcinogens. The Laboratory is organized into the following research groups with the indicated areas of study:
Metabolism and Molecular Mechanisms: Dr. Robert Langenbach (langenb1@niehs.nih.gov)
Growth Control and Cancer: Dr. Richard S. Paules (paules@niehs.nih.gov)
Cancer Biology: Dr. Raymond Tennant (tennant@niehs.nih.gov)
Transgenic Carcinogenesis: Dr. John E. French (french@niehs.nih.gov) and
Dr. Frank W. Kari (kari@niehs.nih.gov)
Toxicology Operations Branch
The NTP was established by the Secretary of Health and Human Services to coordinate toxicology research and testing activities within the Department, to provide information about potentially toxic chemicals to regulatory and research agencies and the public, and to strengthen the science base in toxicology. In its 17 years, the NTP has become the world's leader in designing, conducting, and interpreting animal assays for toxicity.
The Toxicology Operations Branch (Dr. John Bucher, Chief) provides administrative oversight and performance of a number of NTP activities including: (1) the design, review, conduct, and reporting of toxicity and carcinogenicity studies; (2) the Report on
Carcinogens; and (3) the Interagency Coordinating Committee on Validation of Alternative Methods. Additional functions include activities related to maintenance and development of
data capture and retrieval systems, the central data repository, and the NTP presence on the World Wide Web, as well as providing central expertise in the development and administration of contracts for procurement of goods or services in support of the NTP and NIEHS scientific activities.
General Toxicology: Dr. Rajendra S. Chhabra (chhabrar@niehs.nih.gov)
Information Systems and Central Files: Dr. William C. Eastin (eastin@niehs.nih.gov)
Report on Carcinogens: Dr. C. W. Jameson, Head (jameson@neish.nih.gov) and
Dr. Ruth M. Lunn, Staff Scientist (lunn@niehs.nih.gov)
Program Operations: Dr. Joseph H. Roycroft (roycroft@niehs.nih.gov)
Alternative Models: Dr. William S. Stokes (stokes@niehs.nih.gov)
The Office of NTP Liaison and Scientific Review (Ms. Sandra Lange) is responsible for communications in general as well as meetings and reviews conducted by the NTP Board of Scientific Counselors. The Office of Special Programs (Dr. Gary Boorman) oversees the conduct of various large-scale, special collaborative studies for which the ETP has a major responsibility, such as the Congressionally mandated investigation of the potential human health hazards associated with exposure to electromagnetic fields. The Office of Risk Assessment (Dr. Christopher Portier) represents the Institute on all risk assessment related activities and coordinates such activities at both the national and international levels.
In addition to its individual research Programs and Laboratories, the DIR has also established specific faculties composed of scientists from different administrative units who share common interests in various scientific subspecialties. These faculties organize seminars and discussion groups on their topic area and advise the Scientific Director concerning scientific initiatives and hiring within the DIR.
The current faculties are:
Alternative Test Systems and Ecotoxicology (Dr. William S. Stokes, Chair)
http://dir.niehs.nih.gov/dirlecm/
http://dir.niehs.nih.gov/dirlecm/#METABOLISM AND MOLECULAR MECHANISMS GROUP
Targeted gene knockout mouse models, stable cell expression systems, roles of
prostaglandin synthases (COX-1 and COX-2) in carcinogenesis, development and differentiation, and the effects of their inhibition by NSAIDs.
http://dir.niehs.nih.gov/dirlecm/#GROWTH CONTROL AND CANCER GROUP
Cell cycle control alterations during carcinogenesis; cell cycle checkpoint signal transduction pathway; ataxia telangiectasia-mutated (ATM) gene product function.
http://dir.niehs.nih.gov/dirlecm/#CANCER BIOLOGY GROUP
Transgenic mouse models for carcinogenesis and mutagenesis; role of cell proliferation, mutation, and gene expression in skin carcinogenesis; role of UV-induced DNA damage and immune suppression in skin cancer
http://dir.niehs.nih.gov/dirlecm/#Transgenic Carcinogenesis
Investigation of environmental carcinogen and gene interactions, carcinogen identification, and host factors in the modulation of carcinogen induced oxidative stress and neoplasia using genetically altered mouse models of human cancer (Dr. French).
Nutritional modulation of immunological and inflammatory processes in response to toxic and carcinogenic challenges; research emphases placed
on the role of energy balance (calorie restriction) and dietary antioxidants
(Dr. Kari).
http://dir.niehs.nih.gov/dirtob/
http://dir.niehs.nih.gov/dirtob/chhabra.htm
Responsible for the design, conduct, and reporting of the majority of the chemical toxicology and carcinogenesis studies carried out by the NTP.
http://dir.niehs.nih.gov/dirtob/eastin.htm
Responsible for the collection and dissemination of information from all NTP studies. This group also supports the presence of the NTP and the ETP on the World Wide Web (http://ntp-server.niehs.nih.gov) and oversees the electronic capture of all data from NTP studies carried out at contract laboratories.
http://dir.niehs.nih.gov/dirtob/jameson.htm
Responsible for all activities relating to the writing and review of the Report on Carcinogens
http://dir.niehs.nih.gov/dirtob/roycroft.htm
Responsible for assembling the contracting instruments, for coordinating the reviews and awards of research contracts, and for monitoring contract performance.
http://dir.niehs.nih.gov/dirtob/stokes.htm
As Director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, responsible for: overall coordination of NIEHS efforts to develop, validate and achieve regulatory acceptance of alternative toxicological testing models and methods; supporting the Interagency Coordinating Committee on the Validation of Alternative Toxicological Methods (ICCVAM); and implementation of Congressional directives concerning promotion of the use and acceptance of alternative models and methods by other agencies of the Federal Government.
Breast and Prostate Cancer (Dr. Robert Maronpot, Chair)
Chemical Nomination (Dr. Scott Masten, Chair)
Environmental Genome Project (Dr. Jack Taylor, Chair)
Neurosciences (Dr. David Armstrong, Chair)
Human Studies (Dr. Darryl C. Zeldin, Chair)
Oxidative Stress and Free Radicals (Dr. Ronald P. Mason, Chair)
Reproductive and Developmental Biology (Dr. Mitch Eddy, Chair)
Structural Biology (Dr. Robert E. London, Chair)
Toxicokinetics (Dr. Ronald L. Melnick, Chair)
Transgenic Animals (Dr. John Bucher, Chair)
Last updated: June 6, 2002
Please send any comments, corrections, or inquires regarding this page
to
Judi Fleming.