As a structural biology lab, we are interested in understanding the mechanism of molecular machines and their roles in human diseases. Currently we focus on two systems, p97 / ubiquitination system, and vault. p97 is a central hub in cellular protein homeostasis. It is involved in several neurodegenerative diseases, and is also a cancer drug target. We want to gain insights into the molecular architectures of p97 in complex with various cofactor proteins and poly-ubiquitinated substrates. We are investigating the specificity of p97 towards ubiquitin chains with various topologies. Our findings will elucidate the molecular mechanism of human p97. Vault is the largest ribonuclear protein in many eukaryotes including human. It is a membraneless organelle. Despite the fact that vault has been studied for thirty years, its function remains elusive. Overexpression of major vault protein (MVP) correlates with drug resistance in cancer cells. However, the mechanism is completely unknown at the molecular level. We are investigating the structures of vault components and using proteomic and imaging techniques to address the molecular function of vault. There are two major techniques used in the lab: X-ray crystallography and cryo-electron microscopy.
Stanford University and Howard Hughes Medical Institute
California, USA
- Biophysics and Structural Biology
2016
University of California Los Angeles
California, USA
Ph.D. - Molecular Biology
2011
Fudan University
Shanghai, China
B.S. - Biological Sciences
2005
Author Correction: An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.
Author Correction: An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity. Nat Chem Biol. 2024 Jan; 20(1):129.
PMID: 38040979
Author Correction: An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.
Author Correction: An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity. Nat Chem Biol. 2023 Dec 01.
PMID: 38040979
An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.
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PMID: 37400536
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CAND1 orchestrates CRLs through rock and roll. Cell. 2023 04 27; 186(9):1817-1818.
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K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle.
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Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative. Nat Commun. 2021 01 05; 12(1):121.
PMID: 33402676