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Wei Mi

Assistant Professor of Pharmacology
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About

Titles

Assistant Professor of Pharmacology

Biography

Wei Mi obtained his PhD degree in structural biology at Peking University, Beijing, China. Fascinated by structures of membrane proteins, he came to the US and received postdoctoral training at Purdue University, the University of Washington and Harvard Medical School (HMS). At HMS, he joined the laboratory of Dr. Maofu Liao and used single particle cryo-electron microscopy (Cryo-EM) to determine structures of ATP-binding cassette transporters in lipid bilayer environment. In 2019, Dr Mi joined the Department of Pharmacology at Yale University School of Medicine. The focus of his research is to dissect mechanisms of membrane proteins involved in lipopolysaccharide (LPS) synthesis and regulation with genetic, biochemical, and structural approaches.

Appointments

Education & Training

Postdoctoral Research Fellow
Harvard Medical School (2018)
Postdoctoral Research Fellow
the University of Washington (2014)
Postdoctoral Research Fellow
Purdue University (2012)
PhD
Peking University (2008)
BS
Hebei University, Microbiology (2003)

Research

Overview

Antibiotic resistance is one of the most pressing public health challenges of our time, demanding new druggable targets, especially for Gram-negative bacteria. Compared with Gram-positive bacteria that have only a plasma membrane, Gram-negative bacteria have an additional unique outer membrane (OM). The OM has an asymmetric lipid structure, with phospholipids in the periplasmic leaflet and lipopolysaccharides (LPS) on the cell surface. Tightly packed LPS molecules form a remarkable permeability barrier against many antibiotics, including large polar molecules and hydrophobic agents. Because of the essential roles played by LPS in antibiotic resistance and bacterial viability, its biogenesis is an attractive target for antibacterial agents. Several inhibitors that target LPS synthesis and transport are under development as promising antibacterial candidates. However, proteins involved in the regulation of LPS biogenesis have not received a great deal of attention mainly because little is known about its regulation. Since very high or low amounts of LPS are lethal to cell viability, regulation of LPS biogenesis provides a potential opportunity for developing valuable antibiotics. By focusing on understanding how LPS biogenesis is regulated in Escherichia coli, we will provide new molecular mechanistic insights and identify novel targets and approaches for antibiotic development.

It has been known for more than two decades that LpxC, a key enzyme in LPS synthesis, determines LPS levels and that FtsH-dependent proteolysis in Escherichia coli primarily regulates LpxC cellular concentrations. However, how FtsH adjusts its protease activity to specifically regulate LpxC turnover rate according to cellular status is not clear. Recently, genetic analyses and in vivo studies suggested that two essential membrane proteins LapB (YciM) and YejM regulate FtsH protease activity, but there have been no in vitro studies on the regulatory mechanisms. The Mi lab established the first assays to reconstitute LpxC degradation in vitro. We have recently determined the cryoEM structure of YejM/LapB complex structure, elucidating the functions of these key membrane proteins in regulating LPS synthesis.

Medical Subject Headings (MeSH)

Bacteria; Cell Wall; Cryoelectron Microscopy; Lipid A; Lipid Bilayers; Membrane Proteins; Penicillin-Binding Proteins; Phospholipids; Shock, Septic

Research at a Glance

Yale Co-Authors

Frequent collaborators of Wei Mi's published research.

Publications

2024

2023

2022

2020

2018

2017

2015

2010

Academic Achievements & Community Involvement

  • honor

    Dorsett L. Spurgeon Distinguished Research Award

  • honor

    Outstanding Postdoctoral Fellow Award

  • honor

    Mercedes-Benz Shujuan Scholarship

Get In Touch

Contacts

Academic Office Number
Lab Number

Administrative Support

Locations

  • Mi lab

    Lab

    Sterling Hall of Medicine, B-Wing

    333 Cedar Street, Ste A, Rm 251

    New Haven, CT 06510

Events