Colin C. C. Wu, Ph.D.
We are exploring the role of the ribosome in stress response signaling pathways and translational regulation in mammalian systems. To this end, we have developed an improved ribosome footprint profiling methodology that allows us to monitor both the positions and the in vivo functional states of individual ribosomes. Most projects in the laboratory incorporate high-throughput genome-wide approaches, computational tools, and biochemical approaches to define the molecular mechanisms of these pathways in vivo. Our long-term goal aims to congregate actionable insights that can be used to guide the prevention and treatment of human diseases.
1) translational control, 2) ribosome, 3) RNA quality control, 4) RNA biology, 5) protein synthesis
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.
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 3 references to firstname.lastname@example.org.
Selected Recent Publications
- Cell. 182(2): 404-416, 2020. [ Journal Article ]
High-resolution ribosome profiling defines discrete ribosome elongation states and translational regulation during cellular stress.Mol Cell. 73(3): 959-970, 2019. [ Journal Article ]
- Mol Cell. 66(2): 194-205, 2017. [ Journal Article ]
- EMBO J.. e106449: 2021. [ Journal Article ]
- eLife. 8: e49117, 2019. [ Journal Article ]
Dr. Wu received his bachelor’s degree from Chiao Tung University in Taiwan, and then his doctoral degree from the Institute of Molecular Biology at Academia Sinica. He undertook his postdoctoral training at Johns Hopkins University, where he became fascinated with RNA biology and the ribosome. During this time, he investigated the molecular mechanisms of translational regulation by the ribosome and became interested in post-transcriptional regulation of gene expression and ribosome homeostasis. He joined the RNA Biology Laboratory at NCI-Frederick as an NIH Stadtman tenure-track investigator in the fall of 2020 to establish the Translational Control of Gene Expression Section.
|Britnie Santiago Membreno||Postbaccalaureate Fellow (CRTA)|
|Mohammad Sina Shafieinouri||Postbaccalaureate Fellow (CRTA)|
|Indra Sharma Ph.D.||Research Fellow|