Our laboratory is broadly interested in translational regulation during cellular stress, especially by the ribosome, ribosome-associated factors, and RNA binding proteins. We employ an integrated approach, combing mass spectrometry, CRISPR screens, high-throughput chemical probing, ribosome profiling, biochemical techniques, and computational tools to identify and characterize novel factors involved in stress sensing and fine-tuning the translational output.

Protein synthesis is essential in all cells. As such, a continuous flow of ribosomes along mRNAs needs to be maintained to support a healthy proteome. Ribosome stalling occurs under a variety of cellular stress conditions, including nutrient deprivation, hypoxia, and oxidative stress. To gain higher resolution into ribosome dynamics in vivo, we have developed an improved ribosome footprint profiling methodology that reveals not only the positions but also the functional states of individual ribosomes transcriptome-wide (Wu et al., Mol Cell 2019). If a stalled ribosome cannot be resolved before a trailing ribosome catches up, ribosome collisions occur. We recently discovered that colliding ribosomes serve as a platform that recruits collision-sensing factors and triggers two inter-related but distinct signaling pathways– the ribotoxic stress response and the integrated stress response– to regulate cell fate decisions (Wu et al., Cell 2020). We are now investigating the molecular mechanisms of this process and its potential implications in normal cell physiology during development and in disease-related settings such as cancer. Additionally, we’re also pursuing how local translation is coupled to RNA decay and cellular stress responses.

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Available Positions

We are looking for motivated postdoctoral fellows to join and contribute to our team. If you are interested in our research, please send your C.V., a statement of research interests, and the names and contact details of 2 references to colin.wu2@nih.gov.