Sichen Susan Shao, Ph.D.
We aim to understand the molecular mechanisms that determine the fate of new proteins using in vitro reconstitution, cell biology, and structural biology approaches. Protein biosynthesis is a complex process encompassing translation, protein folding and posttranslational modifications, and selective targeting to the correct cellular location. Each step is subject to extensive regulation and quality control that is essential for maintaining cellular homeostasis and preventing disease. The Shao lab aims to dissect the mechanistic basis of these biosynthetic, regulatory, and quality control events using biochemical, cell biology, and structural biology strategies.
Our approaches center on: 1) biochemically reconstituting protein biosynthesis and quality control processes using cell culture, cell lysate-based, and completely purified systems; 2) developing methods and assays to identify, uncouple, and functionally analyze the individual steps and components of each process; and 3) using these methods to isolate biologically-relevant complexes for structural analysis, primarily via single-particle electron cryo-microscopy (cryo-EM). Recently, these strategies have identified new protein targeting and quality control factors, elucidated the mechanisms utilized by these factors to specifically recognize rare substrates and direct them to the appropriate fates, and revealed the molecular details of these interactions.
Our current interests are focused in two main areas. First, following up on previous work on a ribosome-associated protein quality control pathway, we aim to identify and characterize additional regulatory and quality control pathways that interface with mammalian ribosomes upon perturbations to protein translation. Second, we are interested in the machinery and mechanisms that facilitate membrane protein targeting, folding, and assembly at the endoplasmic reticulum and mitochondria. The long-term goal of our lab is to understand in molecular detail the mechanisms underlying these fundamental cellular processes.
Shao S and Hegde RS. (2011) A calmodulin-dependent translocation pathway for small proteins. Cell 47:1576-88.
Shao S*, von der Malsburg K*, and Hegde RS. (2013) Listerin-dependent nascent protein ubiquitination relies on ribosome subunit dissociation. Mol. Cell 50:637-48.
Shao S, Brown A, Santhanam B, and Hegde RS. (2015) Structure and assembly pathway of the ribosome quality control complex. Mol. Cell 57:433-44.
Brown A*, Shao S*, Murray J, Hegde RS, and Ramakrishnan V. (2015) Structural basis for stop codon recognition in eukaryotes. Nature 524:493-6.
Shao S, Rodrigo-Brenni MC, Kivlen MH, and Hegde RS. (2017) Mechanistic basis for a molecular triage reaction. Science 355:298-302.
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