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Metabolism & Molecular Mechanisms Group

Physiological Roles for COX-1 & COX-2

Robert Langenbach, Ph.D.
Robert Langenbach, Ph.D.
Principal Investigator - Retired
Special Volunteer
Tel (919) 541-7558
Fax (919) 541-1460
langenb1@niehs.nih.gov
P.O. Box 12233
Mail Drop C4-09
Research Triangle Park, North Carolina 27709
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Research Summary

The cyclooxygenases, COX-1 and COX-2, are the target enzymes for a class of drugs known as nonsteroidal antiinflammatory drugs (NSAIDs). While both isoforms have important roles in the maintenance of normal physiology and also contribute to the development of various pathological conditions; little is known about the individual functions of the two isoforms.

 

A major goal of Metabolism & Molecular Mechanisms Group has been to use COX-1 or COX-2 deficient mice to identify the individual physiological and pathophysiological roles of the two COX isoforms. A long standing interest of the laboratory has been to elucidate the mechanisms by which COX-1 and COX-2 contribute to tumor development (Figure 1) and concomitantly determine if both isoforms are suitable targets for chemoprevention. Additionally, the group has investigated the fetal and postnatal developmental roles of each COX-1 and COX-2. The above studies, as well as new studies investigating the roles of prostaglandin receptors in tumor development, constitute the major areas of research in the laboratory.

 

Effects of COX deficiency on skin tumor numbers and morphology
Figure 1. Effects of COX deficiency on skin tumor numbers and morphology.

Major areas of research:

  • Identifying the physiological and pathophysiological roles of COX-1and COX-2
  • Understanding the fetal and postnatal developmental roles of COX-1and COX-2

 

Current projects:

  • Determine the contributions of the PGE2 receptors to skin tumor development
  • Identify differences in the PGE2 mediated signaling pathways mediated by EP2 and EP4 and their roles in skin tumor development

 

Robert Langenbach, Ph.D., leads the Metabolism and Molecular Mechanisms Group within the Laboratory of Toxicology and Pharmacology. He earned his Ph.D. in 1966 at The University of Nebraska. He has published 134 peer-reviewed articles in leading biomedical journals as well as several book chapters. He served as an Associate Professor at The University of Nebraska Medical Center before joining NIEHS in 1983.

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