Roger F. Duncan

Affiliated Faculty

Associate Professor

Molecular Microbiology & Immunology, Molecular Pharmacology & Toxicology
Keck School of Medicine
School of Pharmacy

Research Topics

  • DNA & RNA
  • Toxicology

Research Overview

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.