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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Genomic profiling in nuclear receptor-mediated toxicity

Courtney G Woods1, John P Vanden Heuvel, Ivan Rusyn

  • 1Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599-7431, USA.

Toxicologic Pathology
|June 15, 2007
PubMed

Insights

Genomics is crucial for understanding nuclear receptors (NRs) and their role in drug development and toxicity. This approach helps identify drug targets and biomarkers for chemical toxicants affecting physiological responses.

Area of Science:

  • Pharmacology and Toxicology
  • Genomics
  • Molecular Biology

Background:

  • Nuclear receptors (NRs) regulate numerous physiological processes, making them key targets for drug development.
  • NR ligands, including pharmaceuticals and environmental chemicals, can elicit adverse health effects.
  • Understanding NR-mediated toxicity is complex due to overlapping biological pathways.

Purpose of the Study:

  • To review the application of genomics in studying nuclear receptors.
  • To highlight the role of genomics in drug discovery, toxicity assessment, and understanding NR mechanisms.
  • To focus on specific nuclear receptors: PPAR, CAR, PXR, RXR, LXR, FXR, and AHR.

Main Methods:

  • Gene expression profiling using microarrays and other genomic technologies.
  • Simultaneous analysis of thousands of genes to discern toxicological mechanisms.
  • Global approaches to comprehensively probe complex NR-regulated networks.

Main Results:

  • Genomics provides sensitive tools for identifying mechanisms of therapeutic and environmental chemical toxicity.
  • Genomic profiling is essential for identifying drug targets and biomarkers of exposure and toxicity.
  • Genomics facilitates understanding of both NR-dependent and NR-independent events.

Conclusions:

  • Genomics is indispensable for advancing drug discovery, design, optimization, and risk assessment of NR-activating toxicants.
  • Future research and development in nuclear receptor pharmacology will heavily rely on genomic profiling.
  • This review emphasizes the pivotal role of genomics in unraveling NR functions and impacts.

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