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Protein Homeostasis in Development and Aging

Protein homeostasis (proteostasis) is achieved by a conserved network of quality control pathways that support the production of correctly folded proteins, prevent protein misfolding, and remove potentially harmful protein species. However, the proteostasis network has a limited capacity, and its disruption leads to protein aggregation that compromises both cellular and organismal viability. Recent studies have identified cell-nonautonomous regulation of the proteotoxic stress response, suggesting the existence of intricately balanced proteostasis networks that are important for the integration and maintenance of the organismal proteome. Our research aims to understand the dynamic regulation of proteolytic pathways that integrate environmental and physiological changes. Detailed analysis of the cellular and tissue-wide coordination of proteostasis will allow us to build a global picture of conserved protein degradation networks that are important for securing the organismal proteome in health and disease. Our laboratory aims to unravel the interplay between proteolytic networks at the molecular, cellular, and organismal levels and to define adaptive mechanisms that ensure their integrity in response to environmental stresses or inherited disease-associated mutations.