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Michael YaffeBiosketchAssociate Professor, Biology and Biological Engineering The goal of our research is to understand how protein phosphorylation controls progression through the cell cycle at the molecular level and how defects in phosphorylation bypass normal cell cycle checkpoints and lead to human cancer. We also study how protein and lipid phosphorylation controls the inflammatory response in phagocytic cells. Research SummaryCells activate complex signaling pathways in response to stresses and injuries such as DNA damage, hypoxia, and bacterial or viral infection. These pathways control cell cycle progression, coordinately regulate patterns of gene expression and/or initiate programmed cell death by activating protein serine/threonine kinases that phosphorylate critical downstream targets. Mutations in signaling pathways that normally respond to either DNA damage or to disruption of the mitotic spindle, for example, play critical roles in the genesis of most human cancers. Similarly, hypoxia and infection cause dysregulation of cell signaling pathways in phagocytic cells, causing tissue damage in auto-inflammatory diseases and multiple organ failure in sepsis. How are these signaling pathways assembled? What are the key molecules involved? How does their phosphorylation on serine and threonine residues regulate protein-protein interactions to control the cell cycle in epithelial cells or regulate the production of inflammatory mediators by phagocytic cells? Our lab uses a broad proteomics approach to decode how these cell signaling pathways are “wired” using bioinformatics, combinatorial chemistry, cell biology, physical biochemistry, structural biology and molecular genetics. |
