Cells use an intricate network of intracellular signaling molecules to translate environmental changes, sensed via surface receptors, into cellular responses. Despite the prominent role that these networks play in life itself, we still lack a comprehensive understanding of how extracellular information is conveyed through them into specific bioactivities and fate decisions. In order to rationally manipulate cell fate, which could fundamentally change the way that we currently treat human diseases, first we need a systematic understanding of how signaling is initiated and propagated inside the cell. My primary research interest is to understand the cellular and molecular determinants of signaling specificity by cell surface receptors.
To address this important question, we use cytokines as a model system. Cytokines are a large family of secreted ligands that control every aspect of the mammalian physiology. They act as the major source of mid- and long-distance communication between cells, ensuring the coordinated response between different cell subsets. A clear example of this can be found in their regulation of the immune response. Cytokines critically contribute to initiate, maintain and define the type of immune response generated upon an external harm, thus making them highly relevant to human health. Indeed, cytokines are often found dysregulated in many human disorders including inflammation, cancer and auto-immunity. Despite their high clinical value, very few cytokines are used in the clinic, due to the high toxicity associated with their use. A better understanding of the molecular bases for cytokine-induced signaling and activities, could help us to design more efficient and less toxic therapies.
This program aims to tackle two important questions/objectives. The first one focuses on understanding the molecular bases defining signal activation by cytokines. The second one aims at use the information generated from objective 1 to engineer cytokine variants with a more defined set of biological responses. The primary research interest of the project is IL-6, a well-studied cytokine that plays a crucial role in immune regulation by controlling the intensity and duration of the inflammatory response. The information generated from these objectives will provide us with new insight into how cytokines elicit such complex biological responses, which in turn will allow us to design more targeted therapies with reduce toxicities.
