The Genereux lab at the University of California, Riverside
To function properly inside the cell, proteins must achieve their native three-dimensional conformation, and be trafficked to the appropriate subcellular location. Failure at either of these steps deprives the cell of that protein's function, and is the basis of a variety of human diseases. Furthermore, misfolded and mislocalized proteins present a further threat, due to their potential to form toxic conformations. The cell maintains the integrity of the proteome through an extensive and integrated protein homeostasis network of chaperones, degradation factors, and trafficking machineries. Stresses, such as mutations, metabolic disregulation, or exposure to environmental toxins, can overwhelm these machineries. In this case, protein homeostasis is restored by physiological mechanisms that remodel the chaperone environment to prevent misfolded protein accumulation. Although the relevance of these pathways to both fundamental biology and to human health are well established, we still lack the techniques to answer molecular questions of proteostasis across the proteome and in living cells. These questions include: Which proteins misfold in response to specific stresses? and How does stress affect protein partitioning within the cell? Our laboratory applies quantitative proteomics approaches to characterize protein conformation and trafficking and help answer these vital questions. We are particularly interested in how stress and stress-responsive signaling affect molecular properties of the proteome.