The Molecular Underpinnings of Redox Regulation and Oxidative Stress

Many environmental toxins provoke a rise in cellular reactive oxygen species (ROS) that can damage cellular macromolecules, potentially triggering apoptotic signaling. However, ROS are also necessary components of growth factor, cytokine and immune signaling and may be involved in aberrant proliferative signaling that is the hallmark of cancer. Thiol-containing proteins and small molecules are important targets of ROS action, where reversible oxidation can act as a molecular switch to modulate function and regulate cell signaling pathways. Thiol oxidation is also crucial for protein folding, protein secretion and protein trafficking. While redox "imbalance" is widely regarded as the cause of ROS-dependent pathology, we have only a limited understanding of how ROS generation is associated with normal cell signaling. Furthermore, antioxidants have conflicting effects when used as dietary supplements or chemotherapeutics. The need has never been greater for research scientists, physician scientists, scientists from governmental agencies as well as those from industry to come together in this highly interdisciplinary setting to exchange ideas and perspectives and foster new collaborative research interactions. By bringing together investigators with varied expertise in biophysical methods, bioinformatics and animal model systems, with physicians focused on disease processes, the meeting is expected to further stimulate collaborations and catalyze scientific progress as has been exemplified by the successes of the previous meetings.

This conference is in its fourth cycle after three very successful meetings in the U.S. and Italy in 2006, 2008 and 2010. The highly international flavor of this meeting is reflected in the U.S.- and France-based chair and vice chair, respectively, and a diverse range of speakers from around the globe. Topics will include disulfide bond formation in intraorganellar protein folding, chemical biology of reactive oxygen species (ROS) generation and action, and how perturbations in the localized reactive oxygen, nitrogen and sulfur redox environment can alter signaling and lead to disease. Significant emphasis will be placed on cellular signaling dysfunction from environmental stresses and their link to cancer development. Participation by junior researchers in this conference will also be enhanced through a preceding Gordon Research Seminar with keynote speaker Mike Marletta and speakers and discussion leaders chosen from among the graduate student and postdoctoral community in this field.