John C. Wilkinson
My laboratory is examining the role of the intrinsic cellular suicide program known as apoptosis in the pathogenesis of human disease. We are currently focused on the study of two factors, X-linked inhibitor of apoptosis (XIAP) and apoptosis inducing factor (AIF). These molecules directly regulate the apoptotic process, but also possess signaling properties that are distinct from their roles during cell death. XIAP is a highly efficient inhibitor of caspases, the predominant biochemical mediators of apoptosis, but also plays a significant role in regulating signal transduction through the TGF-b, JNK, NF-kB, and copper homeostasis pathways. In contrast, AIF promotes cell death by caspase independent means, but also plays a pro-survival role in vivo by functioning as an NADH-oxidase and regulating mitochondrial function. We have determined that XIAP and AIF associate in living cells with the ability to co-regulate. Both XIAP and AIF are elevated in a variety of human cancers, and our research efforts are currently focused on evaluating their roles in the process of tumorigenesis. We address our research questions by utilizing a variety of techniques spanning the disciplines of molecular biology, biochemistry, and in vivo tumor biology.
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