All newly-synthesized polypeptides have to be folded into their three-dimensional structures to be functional. Many proteins have to reach destinations other than cytosol, the site where protein synthesis occurs. In addition, a majority of proteins constantly undergo post-translational modification in response to a wide variety of cellular signals. Therefore, understanding mechanism and regulation of protein folding, protein translocation and protein processing is an integral part of modern molecular and cell biology. In addition, errors in these processes cause diseases ranging from Alzheimer's to Diabetes. Protein folding and processing is one of the major research focuses in our department. Faculty in this area engage in a number of research topics including the unfolded protein response; structure and function of molecular chaperones; heat shock response; protein misfolding in aging and disease; bacterial type III secretion; yeast pheromone processing; protein transport in the secretory pathway; protein targeting and organelle biogenesis.
Structure and function studies in systems biology and the molecular architecture of organelles; development of new technologies and computational tools for proteome analysis with an emphasis on quantitative proteomics and analysis of posttranslational modifications, including phosphoproteomics and analysis of signal transduction pathways.
Mechanisms of membrane-bound protein quality control systems.
Determining the role of molecular chaperones and disulfide catalysts in protein folding and experimental evolution of protein folding.
Protein localization and vesicular transport in the eukaryotic secretory/endocytic pathways using budding yeast as a system and employing biochemical reconstitution, cell biology, genetics and fluorescence resonance energy transfer (FRET) microscopy as methods. Protein trafficking in human neurodegenerative and neurodevelopmental disease. Proteolytic processing by enzymes of the SPC/Kex2/furin family in yeast and metazoans with interest in structure-function relationships and discovery of human furin inhibitors as drug models for infectious, degenerative and neoplastic disease.
Protein-protein and protein-membrane interactions involved in membrane trafficking and organelle structure.
Biochemical aspects of the bacterial response to oxidative stress.
Biochemistry of the human blood clotting system; structural studies of protein-membrane complexes.
Interactions and processing of proteins involved in heme metabolism, the circadian clock, the global carbon cycle, and methylmercury.
Molecular mechanisms of protein biogenesis including protein folding, membrane trafficking, and stress response; structural biology of protein-protein interaction and molecular recognition using X-ray crystallography.
The main focus of our lab is to develop advanced bioinformatics methods to predict 3-dimensional structures of proteins from amino acid sequences and deduce the biological functions based on the sequence-to-structure-to-function paradigm. We are also working on protein design (or inverse protein folding), protein-ligand docking, and drug discovery.