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My laboratory investigates the mechanisms involved in cell death during the innate immune response and oncogenic transformation. We combine molecular, biochemical, cellular biology and bioinformatics approaches to understand the regulation of the apoptotic pathways. |
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Our studies are focused on the signaling pathways that contribute to the activation and deactivation of caspases, essentials proteases required for apoptosis. The main purpose of our research is that by understanding the mechanisms that regulate the caspases we will be able to manipulate cell death of unwanted cells as a treatment for cancer, inflammation and formation of the atherosclerotic plaque.
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One major project in my lab is to identify the proteins that regulate the activation and activity of the inflammatory and killing caspases during monocyte-macrophage-dendritic cell differentiation. This includes the isolation of regulatory proteins and the dissection of the signaling pathways that modulate apoptosis.
We showed that some PKC isoforms act as pro-apoptotic factors phosphorylating caspase-3 and promoting its activity. These pathways may |
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change during differentiation thus allowing the cells to regulate their apoptotic commitment differently depending on their differentiation’s stage.
We have demonstrated a differential role of inflammatory and anti-inflammatory cytokines in the control of the apoptotic machinery of leukocytes. |
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Furthermore, plant flavonoids are being investigated due to their potential to induce apoptosis in cancer cells and decrease inflammation. These findings may provide a new approach |
to regulate the number of unwanted cells during inflammation.
In this context, one of our main interests is to understand the role of kinases, phosphatases and reactive oxygen species in the regulation of caspases and the contribution of the mitochondria during activation and monocyte apoptosis. These results should contribute to a better understanding of basic mechanisms during sepsis, cancer and the formation of the atherosclerotic plaque. |
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A second area of research involves the characterization of signals produced by dying cells to recruit and promote the clearance of apoptotic bodies by phagocytic cells like the macrophages. We are using biochemical and a proteomic approaches to characterize a compounds produced by dying cells that are chemotactic for macrophages. In addition, using a bioinformatics approach and with the availability of the human proteome, we are trying to characterize new substrates of caspases. These ‘in-silico experiments’ should allow us to identify additional targets of caspases that once validated molecularly can be used to mark unwanted cells for removal by phagocytic cells. |
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