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Your Environment. Your Health.

Pharmacogenetics Group

CAR Activation & Regulatory Mechanisms

Masahiko Negishi, Ph.D.
Masahiko Negishi, Ph.D.
Principal Investigator
Tel (919) 541-2404
Fax (919) 541-0696
negishi@niehs.nih.gov
P.O. Box 12233
Mail Drop E4-07
Research Triangle Park, North Carolina 27709
Delivery Instructions
CAR Liver Illulstration - Phenobarbital, other xenobiotics, growth factor receptors, nen-genomic actions, genomic actions, target gene, regulation of cell cycle/cell growth/cell death, metabolism of xenobiotics, metabolism of endobiotics, metabolism of glucose and lipids, hormonal regulation

Research Summary

Masahiko Negishi, Ph.D., leads the Pharmacogenetics Group and holds a secondary appointment in the NIEHS Signal Transduction Laboratory. The Pharmacogenetics Group investigates the molecular and cellular mechanisms of constitutive androstane receptor (CAR) activation and the regulatory mechanism of CAR-mediated cell growth and death.

Cells respond to environmental exposures by regulating gene expression and altering various types of cellular metabolism. Upon activation by xenobiotics, including therapeutic drugs, the nuclear receptor CAR regulates numerous hepatic genes to counter or promote adverse cell growth and death. The Pharmacogenetics Group investigates the molecular and cellular mechanisms of CAR activation, focusing on those xenobiotics that activate the receptor without the direct binding. Group members also investigate the regulatory mechanism of CAR-mediated cell growth and death to understand environmental diseases such as liver tumors, with the goal of providing biological tools for disease prevention.

The Pharmacogenetics Group also investigates the structure and function of glycosyltransferases. Glycosyltransferases catalyze the transfer of sugars to produce extremely structurally diverse glucosaminylglycans. They are involved in the regulation of various cellular functions, such as cell growth and death, cell-cell interactions and microbial infections. X-ray crystallography and isothermal titration calorimetry are used with the goal of understanding the molecular principle underlying protein-carbohydrate interactions.

Major areas of research:

  • Investigating the molecular and cellular mechanisms of CAR activation
  • Determining the regulatory mechanism of CAR-mediated cell growth
  • Understanding the molecular principle underlying protein-carbohydrate interactions

Current projects:

  • Understanding the xenobiotics that activate CAR without direct binding
  • Developing biological tools for the prevention of environmental diseases
  • Investigating the structure and function of glycosyltransferases

Negishi earned his Ph.D. in biochemistry at Osaka University. He has published 179 peer-reviewed articles in leading biomedical journals as well as 45 review articles and book chapters. He joined NIEHS in 1983.

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