Biochemistry and Molecular Biology Discipline

Center for Proteomics and Molecular Therapeutics

Yale University, PhD in Molecular Biophysics and Biochemistry, 2001
Memorial Sloan-Kettering Cancer Center, Research Fellow, 2002-2004
Brookhaven National Laboratory, Research Associate, 2005-2008

Research

Membrane transport is a fundamental life process that is carried out by membrane channel and transport proteins. We use X-ray crystallography as a primary tool to study the structure and mechanism of medically important membrane transport and channel proteins. The long term goal of our research is to gain a deep understanding of transport mechanism, substrate selectivity and functional regulation. Currently we focus on bacterial proteins that utilize a preexisting proton or sodium gradient to transport their substrates across the cell membrane. We are also interested in integral membrane proteins that transport RNA molecules in eukaryotic cells.

We recently received NIH funding to study Multidrug and Toxin Extrusion (MATE) transporters, which are integral membrane proteins that move structurally unrelated lipophilic cations across the cell membrane by utilizing a preexisting sodium or proton gradient. Bacterial MATE transporters function as multidrug efflux pumps by expelling a cohort of antimicrobial agents from the cytoplasm, whereas their human counterparts mediate the excretion of various cytotoxic metabolites as well as therapeutic drugs. Given their functional relevance to the unwanted resistance to antimicrobials and chemotherapy, molecular structures of the MATE transporters will reveal not only how they transport their substrates across the cell membrane but also how their transport activity can be modulated in order to overcome drug resistance.

Publications

• Wu, H.-H., Symersky, J. and Lu, M. (2019) Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition. Commun. Biol. 2:210. []
• Lu, M. (2019) Structure and mechanism of the divalent anion/Na+ symporter (review). Int. J. Mol. Sci. 20:440. []
• Symersky, J., Guo, Y., Wang, J. and Lu, M. (2018) Structure determination at low-resolution, anisotropic data and crystal twinning. In K. Beis and G. Evans (Eds.), Protein Crystallography: Challenges and Practical Solutions, (pp.140-156). The Royal Society of Chemistry. []
• Rodriguez-Zabala, M., Aza-Carmona, M., Rivera-Pedroza, C.I., Belinchón, A., Guerrero-Zapata, I., Barraza-García, J., Vallespin, E., Lu., M., Del Pozo, A., Glucksman, M.J., Santos-Simarro, F., and Heath, K.E. (2017) FGF9 mutation causes craniosynostosis along with multiple synostoses. Hum. Mutat. 38:1471-1476. []
• Nie, R., Stark, S., Symersky, J., Kaplan, R.S. and Lu, M. (2017) Structure and function of the divalent anion/Na+ symporter from Vibrio cholerae and a humanized variant. Nat. Commun. 8:15009. []
• Radchenko, M., Nie, R. and Lu, M. (2016) Disulfide crosslinking of a multidrug and toxic compound extrusion transporter impacts multidrug efflux. J. Biol. Chem. 291:9818-9826. []
• Lu, M.(2015) Structures of multidrug and toxic compound extrusion transporters and their mechanistic implications (review) Channels 10(2):88-100. []
• Symersky, J., Guo, Y., Wang, J. and Lu, M. (2015) Crystallographic study of a MATE transporter presents a difficult case in structure determination with low-resolution, anisotropic data and crystal twinning Acta Cryst D71 2287-2296.[]
• Radchenko, M., Symersky, J., Nie, R. and Lu, M.. (2015) Structural basis for the blockade of MATE multidrug efflux pumps. Nat. Commun. 6:7995 []
• Lu, M., Radchenko, M., Symersky, J., Nie, R. and Guo, Y. (2013) Structural insights into H⁺-coupled multidrug extrusion by a MATE transporter. Nature Struct. Mol. Biol. 20:1310-1317 []
• Lu, M., Symersky, J., Radchenko, M., Koide, A., Guo, Y., Nie, R. and Koide, S. (2013) Structures of a Na⁺-coupled, substrate-bound MATE multidrug transporter. Proc. Natl. Acad. Sci. USA110:2099-2104 []
• Lu, M., Chai, J. and Fu, D. (2009) Structural basis for autoregulation of the zinc transporter YiiP. Nat. Struct. Mol. Biol. 16, 1063-1067. []
• Lu, M. and Fu, D. (2007) Structure of the zinc transporter YiiP. Science 317, 1746-1748.
• Lu, M. and Steitz, T.A. (2001) Structure of Escherichia coli ribosomal protein L25 complexed with a 5S rRNA fragment at 1.8-Å resolution. Proc. Natl. Acad. Sci. USA 97, 2023-2028.

Jobs

North Chicago offers an easy access to many recreational (downtown Chicago) and scientific (Advanced Photon Source) resources. We currently seek talented individuals to join our lab as graduate students, postdoctoral fellows and research technicians. For postdoctoral candidates, previous experience in membrane protein purification is definitely an asset. For questions regarding hiring, please contact me by email.