Jie Wang

Background

About Jie Wang

My long-term interest is to investigate the mechanisms underlying protein dysregulation in diseases and use this knowledge to help with potential therapeutics. To gain a general knowledge of proteins, in 2009, I started as a Ph. D. candidate at Tsinghua University. Trained as a structural biologist, I gained extensive knowledge of protein production in bacterial and mammalian cells; purification methods including different affinity and chromatography techniques; structural biology related techniques such as crystallization, diffraction data collection, structure determination, and structure-directed analysis; as well as protein biochemistry including interaction analysis and enzymatic kinetics. With these skills, we solved the crystal structure of the plant steroid receptor in complex with its inhibitory protein and demonstrated the steroid-dependent heterodimerization of the receptor/coreceptor ectodomains brings their cytoplasmic kinase domains in the right orientation for competing with the inhibitor and transphosphorylation (Wang et al, Cell Res, 2014). To concentrate more on the disease-related proteins, in 2015, I joined Max Planck Institute of Molecular Cell Biology and Genetics as a postdoc and worked with prion-like proteins that are difficult to purify. This experience not only significantly improved my protein purification skills by utilizing distinct tagging strategies, optimizing expression constructs, and screening protein solubility; but also gave me extensive training on immunofluorescence microscopy and cell-based assays. Using a combination of these techniques, we identified a sequence-specific amino acid code for dozens of proteins that have played a central role in phase separation, a process for establishing membrane-less compartments (Wang et al, Cell, 2018). We also showed that RNA can modulate the phase separation behaviors of these proteins (Maharana, Wang et al, Science, 2018). To better investigate the relevance of protein dysregulation in vivo, in 2020, I joined Whitehead Institute for Biomedical Research as a postdoc to study dysregulated transcription factors in cells. We plan to use gene editing, genome sequencing, super-resolution imaging techniques that are beyond my current cell biology and protein biochemistry skills to investigate dysregulated transcription programs in vivo. With more than 10 years of experience in protein biochemistry and integrated training on cell biology, I hope I can uncover the protein dysregulation mechanisms and provide a foundation for pre-clinical drug development.