Genomic Profiling in Nuclear Receptor-Mediated Toxicity

Courtney G. Woods, John P. Vanden Heuvel, Ivan Rusyn

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

Nuclear receptors (NRs) are attractive drug targets due to their role in regulation of a wide range of physiologic responses. In addition to providing therapeutic value, many pharmaceutical agents along with environmental chemicals are ligands for NRs and can cause adverse health effects that are directly related to activation of NRs. Identifying the molecular events that produce a toxic response may be confounded by the fact that there is a significant overlap in the biological processes that NRs regulate. Microarrays and other methods for gene expression profiling have served as useful, sensitive tools for discerning the mechanisms by which therapeutics and environmental chemicals invoke toxic effects. The capability to probe thousands of genes simultaneously has made genomics a prime technology for identifying drug targets, biomarkers of exposure/toxicity and key players in the mechanisms of disease. The complex intertwining networks regulated by NRs are hard to probe comprehensively without global approaches and genomics has become a key technology that facilitates our understanding of NR-dependent and -independent events. The future of drug discovery, design and optimization, and risk assessment of chemical toxicants that activate NRs will inevitably involve genomic profiling. This review will focus on genomics studies related to PPAR, CAR, PXR, RXR, LXR, FXR, and AHR.

Original languageEnglish (US)
Pages (from-to)474-494
Number of pages21
JournalToxicologic Pathology
Volume35
Issue number4
DOIs
StatePublished - Jun 2007

Fingerprint

Cytoplasmic and Nuclear Receptors
Toxicity
Genomics
Poisons
Pharmaceutical Preparations
Technology
Biological Phenomena
Peroxisome Proliferator-Activated Receptors
Drug Design
Complex networks
Gene Expression Profiling
Biomarkers
Drug Discovery
Microarrays
Gene expression
Risk assessment
Railroad cars
Genes
Chemical activation
Health

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

Cite this

Woods, Courtney G. ; Vanden Heuvel, John P. ; Rusyn, Ivan. / Genomic Profiling in Nuclear Receptor-Mediated Toxicity. In: Toxicologic Pathology. 2007 ; Vol. 35, No. 4. pp. 474-494.
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Genomic Profiling in Nuclear Receptor-Mediated Toxicity. / Woods, Courtney G.; Vanden Heuvel, John P.; Rusyn, Ivan.

In: Toxicologic Pathology, Vol. 35, No. 4, 06.2007, p. 474-494.

Research output: Contribution to journalReview article

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