Research
Our research focuses on the Drosophila Immune Deficiency (IMD) pathway and its mammalian counterpart, the Tumor Necrosis Factor (TNF) pathway. We are always interested in talking to motivated students interested in 499, M.Sc. or Ph. D. projects. Our lab is funded through two operating grants (CIHR and NSERC) and is supported by CFI-funded infrastructure grants.
THE IMD PATHWAY
Drosophila responds to the detection of bacterial DAP-type peptidoglycan through the IMD pathway. The IMD pathway relies on caspase, JNK and NF-kB arms to unleash a robust cellular and humoral response against invading microbes. We are particularly interested in the mechanisms that govern activation of the caspase and JNK arms of the IMD pathway. For example, we recently completed a quantitative evaluation of the entire fly genome for modifiers of JNK activation. In this assay, we demonstrated that the fly PDGF and VEGF Receptor (PVR) pathway acts in a negative feedback loop as an inhibitor of IMD/JNK activation. We are currently studying the PVR pathway in whole animal models of fly immunity.
THE TNF PATHWAY
The mammalian TNF cytokine activates a number of different physiological responses that range from inflammation through differentiation to cell death. Given the evolutionary relationship between the IMD and TNF pathways, we are interested in the regulation of caspase, JNK and NF-kB arms of the mammalian TNF pathway. We recently completed an RNAi-based cell culture survey of the human kinome for novel modifiers of the ability of TNF to induce cell death. In this assay, we identified a role for mitochondrial hexokinase I as an inhibitor of TNF-dependent cell death. We are currently characterizing the molecular basis for interactions between hexokinase I and cell death.