Roger F. Duncan

Roger F. Duncan, PhD

Associate Professor

Pharmacology and Pharmaceutical Sciences

Research Topics

  1. DNA & RNA
  2. Toxicology

Contact Information

  • rduncan@usc.edu
  • 9121 HSC
  • PSC 210A
  • (323) 442-1449
  • (323) 442-1681

Education

AB 1971 Biology - University of California, San Diego
PhD 1978 Biochemistry - University of Hawaii, Manoa

Postdoctoral Research Fellowship:
1979 - 1981 University of Colorado, Boulder
1981 - 1987 University of California, Davis

Roger F. Duncan

Research Interest

Molecular Responses to Cellular Stress; Regulation of Translation

Cellular stress results in many changes in gene expression, and in the activities of proteins within the cell. These changes enhance the ability of cells to survive potentially damaging situations, facilitate the repair of damaged molecules, and increase the recovery of normal cell function. When stress responses are incapable of coping with the stressful situation, or activated inappropriately, deleterious results frequently occur and are associated with pathophysiological conditions. For example, aging-related disabilities, atherosclerosis, and cancer are thought to be caused by oxidative stress; and cell death caused by over-exposure to sunlight or surgical complications can be alleviated by overexpression of protective stress-induced proteins. One area of our research focuses on the identification of these protective proteins and understanding how they improve cell function and viability.

We use several model systems to investigate the molecular responses to cellular stress. We use arterial vascular cells exposed to oxidative stress to model events occurring during early atherogenesis (the formation of arterial plaques that can lead to heart attacks). We are investigating changes in gene expression and specific protein activities caused by exposure to oxidized lipids such as occur in the low density lipoprotein particles (which have been strongly implicated in progression to heart disease). We are also identifying molecules in cell signaling pathways whose activities are significantly increased, promoting cell growth. In other contexts, these proteins can function as oncogenic proteins.

The second model system we study is heat shock, which has proved to be a source of many fundamental discoveries in molecular biology over the past two decades. Our specific focus is the regulation of heat shock protein expression and activity. In one strategy, we dissect and mutate the heat shock protein mRNA to define key sequence elements required for their preferential expression. We are also identifying molecular changes in cell signaling and translational machinery molecules. In collaboration with the key mRNA sequence features, these result in preferential translation of the heat shock protein mRNAs. Further details can be found in the publications listed below.

Biography

Dr. Duncan received his Ph.D. from the University of Hawaii in 1978. He moved to the University of Colorado (Boulder) and the University of California (Davis) for post-doctoral research studies, before joining the University of Southern California School of Pharmacy in 1987, where he is currently an associate professor in the Department of Molecular Pharmacology.

Selected Projects/Publications

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Duncan RF - Rapamycin conditionally inhibits Hsp90 but not Hsp70 mRNA translation in Drosophila: implications for the mechanisms of Hsp mRNA translation. - Cell Stress Chaperones PubMed

Cao T,McKenry MV,Duncan RA,Dejong TM,Kirkpatrick BC,Shackel KA - Influence of Ring Nematode Infestation and Calcium, Nitrogen, and Indoleacetic Acid Applications on Peach Susceptibility to Pseudomonas syringae pv. syringae. - Phytopathology [2006] Jun;96(6):608-15 PubMed

Duncan RF - Inhibition of Hsp90 function delays and impairs recovery from heat shock. - FEBS J PubMed

Cao T,Duncan RA,McKenry MV,Shackel KA,Dejong TM,Kirkpatrick BC - Interaction Between Nitrogen-Fertilized Peach Trees and Expression of syrB, a Gene Involved in Syringomycin Production in Pseudomonas syringae pv. syringae. - Phytopathology  PubMed

Ahmed R,Duncan RF - Translational regulation of Hsp90 mRNA. AUG-proximal 5'-untranslated region elements essential for preferential heat shock translation. - J Biol Chem  PubMed

Duncan RF,Peterson H,Sevanian A - Signal transduction pathways leading to increased eIF4E phosphorylation caused by oxidative stress. - Free Radic Biol Med PubMed

Ahmed R,Duncan RF - Translational regulation of Hsp90 mRNA. AUG-proximal 5'-untranslated region elements essential for preferential heat shock translation. - J Biol Chem  PubMed

Asatryan L,Ziouzenkova O,Duncan R,Sevanian A - Heme and lipid peroxides in hemoglobin-modified low-density lipoprotein mediate cell survival and adaptation to oxidative stress. - Blood PubMed

Schroeter H,Boyd CS,Ahmed R,Spencer JP,Duncan RF,Rice-Evans C,Cadenas E - c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis. - Biochem J  PubMed

Duncan RF,Peterson H,Hagedorn CH,Sevanian A - Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells. - Biochem J PubMed

Koev G,Duncan RF,Lai MM - Hepatitis C virus IRES-dependent translation is insensitive to an eIF2alpha-independent mechanism of inhibition by interferon in hepatocyte cell lines. - Virology PubMed