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Paul J. Anderson, M.D., Ph.D.

Photo of Paul Anderson

TitleK. Frank Austen Professor of Medicine
DepartmentDivision of Rheumatology, Immunology and Allergy
InstitutionBrigham and Women's Hospital
AddressSmith Building, Room 608
 One Jimmy Fund Way
City, State, ZipBoston, MA 02115
Phone(617) 525-1202
E-Mailrics.bwh.harvard.edu
Websiteanderson.bwh.harvard.edu/
Research FieldImmunology
Award Year1990

Research

Our major research focus is the post-transcriptional regulation of pro-inflammatory protein expression. The major post-transcriptional mechanisms studied in the lab are protein translation and mRNA stability. Many mRNAs encoding pro-inflammatory proteins possess regulatory elements that determine rates of mRNA translation and decay. The most common post-transcriptional control element is the adenine/uridine-rich element (ARE). We have identified a family of RNA-binding proteins that target the ARE to dampen the expression of pro-inflammatory proteins. The translational repressors include TIA-1 and TIAR, related ARE-binding proteins that repress the translation of mRNAs encoding TNF, IL-1, IL-6, MMP, and COX-2. The destabilizing factors include TTP, BRF1 and BRF2, related proteins that promote the degradation of these same mRNAs. Mutant mice that lack these regulatory proteins develop spontaneous arthritis, a consequence of overproduction of pro-inflammatory proteins.

We are also working on general translational control mechanisms in cells subjected to environmental stress, such as heat, UV radiation, or oxidation. Under these adverse conditions, cells reprogram protein translation. The translation of most proteins is decreased, but the translation of heat shock proteins and DNA damage repair proteins is increased, allowing the cell to recover from stress-induced damage. The molecular mechanisms used to turn off protein translation during stress are very similar to the mechanisms used to repress the translation of mRNAs encoding inflammatory proteins.

Keywords


1990 Scholars


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