Title of the presentation:
A systems approach to studying arsenic binding to cellular proteins.

Biography:
Dr. Chris Le is Professor and Director of the Analytical and Environmental Toxicology Division at the University of Alberta. He is an elected Fellow of the Royal Society of Canada. He holds an inaugural Canada Research Chair in Bioanalytical Technology and Environmental Health since 2001. He is cross-appointed in the Departments of Laboratory Medicine and Pathology, Chemistry, and Public Health Sciences. He is Guest Professor at Dalian Institute of Chemical Physics, Chinese Academy of Sciences since 2001.

Short summary of research interests:
With expertise in bioanalytical chemistry and environmental sciences, Dr. Le pursues multidisciplinary research in bioanalytical technology, environmental chemistry and toxicology, and DNA damage and protein biomarkers. His group develops innovative bioanalytical techniques and makes use of these techniques to understand the effects of environment on human health.

Abstract:
Arsenic compounds have been recognized as both human carcinogens and therapeutics for treating acute promyelocytic leukemia. However, the mechanism(s) of action responsible for their carcinogenicity and therapeutic property remains unclear. We hypothesize that arsenic binding to cellular proteins is a possible mechanism. Recent studies have shown binding of trivalent arsenicals to cysteines in proteins. However, studies aimed at characterizing arsenic-binding proteins from treated cells have only been able to identify a few highly abundant proteins. A large variety of potential arsenic-binding proteins present at lower concentrations are undetectable by current analytical techniques. To confront this challenge, we have developed an approach of affinity capturing of arsenic-binding proteins followed by mass spectrometry characterization of the captured proteins. The combination of affinity capturing and tandem mass spectrometry enabled selection and identification of large number of arsenic-binding proteins in arsenic-treated cells. Analysis of subcellular fractions of A549 human lung carcinoma cells identified 50 proteins in the nuclear fraction, and 24 proteins in the membrane/organelle fraction that could bind to arsenic. Many of these identified arsenic-binding proteins have important biological functions, including DNA repair and maintaining genome stability, modulating the redox status of cells, and affecting apoptosis.