dbzach.fst.msu.edu

Exposures to certain environmental chemicals, drugs and natural products can result in toxicity in humans and wildlife. The adverse effects of some of these chemicals are mediated by nuclear receptors, which regulate gene expression. Our focus is on understanding the gene expression changes involved in nuclear receptor-mediated toxicity in the liver and endocrine system. We use in vivo rodent and in vitro cell line models to compare human, mouse, and rat responses. Ultimately, our aim is to decrease uncertainties in cross-species and cross-model extrapolations and better model relevant human exposures.

To understand the role of nuclear receptors in toxicity, we explore species-conserved and species-specific toxic responses and the molecular profiles that precede them. Our toxicogenomic approach combines the study of classical toxic endpoints with gene expression, metabolite, and gene regulatory element profiling.  This includes microarray technology, chromatin immunoprecipitation, NMR, mass spectrometry, and histology.  Combining these methods allows us to study the steps from nuclear receptor activation to toxicity.

Our in-house bioinformatics group develops databases and tools to facilitate data management, analysis and integration.  These include TIMS dbZach (data management), Tox-LIMS (sample tracking), and computational toxicology tools in support of data analysis, dose response modeling, and identification of nuclear receptor binding sites within the human, mouse, and rat genomes.

What is dbZACH?

dbZACH is a toxicogenomic information management system, built on a relational database and Java technology, used to store a variety of data generated or otherwise relevant to the Zacharewski lab. The goal of the project is to create a local data management product that is capable of serving the needs of small toxicology laboratories. The database is in the process of being migrated to Oracle 10g, and will operate in a SuSE Linux 9 on an IBM x255 eServer. Currently we have a second port of dbZach in aDB2 environment.

Ongoing Projects

• dbZach Statistics: Selected statistics about data within dbZach
• Current Ozone Levels: Current O3 levels for the Lansing Area.

Who are the dbZach System developers?

The dbZach System is being developed by the Zacharewski Laboratory Bioinformatics Group, located in 248 National Food Safety and Toxicology Center, at Michigan State University. The Bioinformatics Group plays a supporting role in the ongoing research of the lab.

dbZACH Information and Bioinformatics Group Documentation

• dbZACH Frequently Asked Questions (FAQ)
• Bioinformatics Group Guidance Documents
• Bioinformatics Quality Assurance Plan

dbZACH Online (Interfaces)

• Clones: Input a clone_id or accession number; returns cluster and functional annotation for the queried clone_id
• Protocols: See SOP (Standard Operating Procedures) of the lab.
• Real-Time PCR Primers: Query for primers currently in dbZach.
• Software Comments Interface: Allows laboratory members and collaborators to comment on our software.

Organizations

Breast Cancer and the Environment Research Centers

Canadian Network of Toxicology Centers

Chemical Manufacturers Association

National Council of the Paper Industry for Air and Stream Improvement

Society of the Plastics Industry

US Environmental Protection Agency

Investigators

Patrick Balaguer INSERM U439, Montpellier, FRANCE

Christoph Benning Department of Biochemistry and Molecular Biology, Michigan State University

Nigel Bunce Chemistry/Biochemistry Department, University of Guelph, Guelph, Ontario, Canada

Susan Conrad Department of Microbiology and Molecular Genetics, Michigan State University

Ed Carney Developmental & Reproductive Toxicology, Dow Chemical Company, Midland, MI

CC Chang Department of Human Development & Pediatrics, Michigan State University

Karen Chou Department of Animal Science, Michigan State University

Bhaskar Gallapudi Genetic Toxicology, Dow Chemical Company, Midland, MI

Chris Gennings Department of Biostatistics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA

John Giesy Department of Zoology, Michigan State University

James Gieger Department of Chemistry, Michigan State University

Barry Glickman Department of Biology, University of Victoria, Victoria, British Columbia, CANADA

Geoff Hammond London Regional Cancer Center, Department of Pharmacology and Toxicolgy, University of Western Ontario, London, Ontario, Canada

Sandra Haslam MSU Breast Cancer and the Environment Research Center, Department of Physiology, Michigan State University

Leslie Kuhn Department of Biochemistry and Molecular Biology, Michigan State University

John J. LaPres Department of Biochemistry and Molecular Biology, Michigan State University

Brian McCarry Department of Chemistry, McMaster University, Hamilton, Ontario, CANADA

John McCracken Department of Chemistry, Michigan State University

Richard Miksicek Department of Physiology, Michigan State University

Karl Olson Department of Physiology, Michigan State University

Peter Saama MSU Animal Breeding and Genetics Group - Quantitative Gentics Lab, Department of Animal Science, Michigan State University

Steve Safe Department of Veterinary Physiology & Pharmacology, Faculty of Toxicology, Texas A&M University

Richard Schwartz Department of Microbiology and Molecular Genetics, Michigan State University

Cheryl Sisk Director, Neuroscience Program, Michigan State University

Steve Triezenberg Department of Biochemistry and Molecular Biology, Michigan State University

Jim Trosko Department of Human Development & Pediatrics, Michigan State University

Glen Van der Kraak Department of Zoology, University of Guelph, Guelph, Ontario, CANADA

Juli Wade Departments of Psychology and Zoology, Michigan State University