Minglei Zhao, PhD

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

PTPN2 copper-sensing relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression.
PTPN2 copper-sensing relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression. Nat Commun. 2024 Aug 13; 15(1):6947.
PMID: 39138174

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.
An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity. Nat Chem Biol. 2023 Nov; 19(11):1384-1393.
PMID: 37400536

CAND1 orchestrates CRLs through rock and roll.
CAND1 orchestrates CRLs through rock and roll. Cell. 2023 04 27; 186(9):1817-1818.
PMID: 37116466

A novel membrane complex is required for docking and regulated exocytosis of lysosome-related organelles in Tetrahymena thermophila.
A novel membrane complex is required for docking and regulated exocytosis of lysosome-related organelles in Tetrahymena thermophila. PLoS Genet. 2022 05; 18(5):e1010194.
PMID: 35587496

Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.
Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition. Nat Commun. 2022 04 05; 13(1):1833.
PMID: 35383169

Structural insights into Ubr1-mediated N-degron polyubiquitination.
Structural insights into Ubr1-mediated N-degron polyubiquitination. Nature. 2021 12; 600(7888):334-338.
PMID: 34789879

Mechanistic insight into substrate processing and allosteric inhibition of human p97.
Mechanistic insight into substrate processing and allosteric inhibition of human p97. Nat Struct Mol Biol. 2021 07; 28(7):614-625.
PMID: 34262183

K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle.
K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle. Nat Chem Biol. 2021 08; 17(8):896-905.
PMID: 34239127

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