Cell & Molecular Biology Program Event
Brian Cunniff

Dr. Brian Cunniff

Cellular and Molecular Biology
University of Vermont

Mitochondrial Architecture, Oxidant Production, and Redox Signaling in Malignant Mesothelioma Cells

Tuesday January 22nd, 2013
11:30 AM
Davis Auditorium

Numerous cancers are characterized as reactive oxygen species (ROS)-driven tumors, where a disruption in ROS production and/or metabolism supports the metastatic progression of the cancer. Our lab is interested in targeting the mitochondrial redox status of malignant mesothelioma (MM) as a means of therapy. We have shown that MM cells exhibit this ROS-driven phenotype with an increase in mitochondrial-derived ROS and increased RNA/protein expression of the primary mitochondrial antioxidant network composed of thioredoxin reductase 2 (TR2), thioredoxin 2 (TRX2) and peroxiredoxin 3 (PRX3). This pathway is responsible for metabolizing up to 90% of mitochondrial-derivedROS. We have devised combinatorial approaches using using both targeted and un-targeted mitochondrial drugs that disrupt mitochondrial architecture, increase mitochondrial oxidative stress and reduce the protein expression of the oncogenic transcription factor FOXM1. We hypothesize that the phenotype resulting from the over-expression of FOXM1 and the mitochondrial antioxidant network enhances the expression of core cell cycle proteins supporting MM tumor survival. These could therefore serve as valuable targets in MM therapy.

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