Title/s: Assistant Professor
Office #: FH-422
- 1988 B.S., Wuhan University, China
- 2001 Ph.D., University of Oklahoma
- 2002-2003 Postdoctoral Fellow, University of Oklahoma
- 2003-2004 Postdoctoral Fellow, UT Southwestern Medical Center at Dallas
- 2004-2009 Postdoctoral Fellow, Brandeis University
Dr. Liu’s research group primarily employs X-ray crystallography in combination with mechanistic, biological and computational methods to study proteins involved in bacterial pathogenesis and human diseases. Following the doctrine of “Structure Determines Function”, our research evolves around determining key protein structures that are mechanistically informative on biochemical processes. Piecing together the obtained structures like snapshots, knowledge on biological functions can be deduced. We aim to apply this knowledge to discover novel antimicrobial methods and conduct structure-based drug design.
1. Discover Novel Antimicrobial Methods to Combat Antibiotic Resistance.
We currently focus on three protein targets involved in difference aspects of virulence expression in pathogenic bacteria. Target 1: on-going studies aim to employ lactonase as a protein therapeutic to disrupt bacterial cell-to-cell communication, quorum-quenching. On Target 2, on-going studies aim to inhibit acylase to disrupt bacterial iron acquisition. On Target 3, on-going studies aim to modulate GabR-dependent transcription regulation to weaken bacterial stress response. These targets are critical for different biological functions but converge on virulence expression in persistent infections such as the lung infection in patients with cystic fibrosis. The targeted pathogens include Pseudomonas aeruginosa, Burkholderia cepacia complex, Klebsiella pneumonia et al, all of which are known for their ability to resist widely used antibiotics such as penicillin. Overall, a variety of approaches including protein engineering, inhibitor design and discovery of super agonistic ligands will be used to exploit the potential of reducing virulence, to bring about novel treatments that overcome antibiotic resistance in bacteria, and to improve the quality of life of patients who suffer from these life-long infections.
2. Structural Enzymology and Structure Based Drug Design
Through collaborative efforts, we are also interested in elucidating the mechanism of allosteric regulators and rational drug design against protein targets in humans. The enzymes in these studies include bacterial Sucrose Synthase and bacterial ADP-Glucose Pyrophosphorylase, which are important in biofuel production. Mammalian GABA Aminotransferase and human Ornithine Aminotransferase are studied as drug targets in neurological disorder and hepatic cancer respectively.
Current publications via PubMed.
- Lee H, Doud EH, Wu R, Sanishvili R, Juncosa JI, Liu D, Kelleher NL, Silverman RB. Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115) J. Am. Chem. Soc. (2015) 137(7), 2628-40.
- Clevenger, K. D. ‡, Wu, R. ‡, Liu, D*., and Fast, W*. n-Alkylboronic acid inhibitors reveal determinants of ligand specificity in the quorum-quenching and siderophore biosynthetic enzyme PvdQ, Biochemistry (2014) 53, 6679-6686.
- Jingling Liao, Chungxiang Wu, Christopher Burlak, Sheng Zhang, Heather Sahm, Mu Wang,Zhong-Yin Zhang, Kurt W. Vogel, Steven M Riddle, Mark Federici, Jeremy Nichols, Dali Liu, Mark Cookson, Todd A. Stone and Quyen Q. Hoang, The Parkinson's disease-associated mutation R1441H in LRRK2 prolongs the “active-state” of its GTPase domain, Proc. Natl. Acad. Sci., (2014) 111(11), 4055-60.
- Salette Martinez‡, Rui Wu‡, Ruslan Sanishvili, Dali Liu, and Richard C Holz, The active site sulfenic acid ligand in nitrile hydratases can function as a nucleophile, J. Am. Chem. Soc., (2014) 136(4), 1186-1189.
- Raji Edayathumangalam‡, Rui Wu‡, Yuguang Wang, Roman Garcia, Wei Wang, Cheryl Kreinbring, Jingling Liao, Todd Stone, Quyen Q. Hoang, Boris Belitsky, Gregory A Petsko, Dagmar Ringe*, and Dali Liu*, Crystal structure of GabR, an auto repressor and transcriptional activator of gabT, Proc. Natl. Acad. Sci., (2013) 110(44), 17820-17825.
- Wade C. McGregor, Danuta M Gillner, Sabina I. Swierczek, Dali Liu and Richard C. Holz, Identification of a Histidine Metal Ligand in the argE-Encoded N-Acetyl-L-Ornithine Deacetylase from Escherichia coli, SpringerPlus, (2013) 2:482.
- Kenneth Clevenger, Rui Wu, Joyce Er, Dali Liu and Walter Fast, Rational design of a transition state analog with picomolar affinity for Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme, ACS Chem. Biol., (2013) 8(10), 2192-2200.
- Ce-Feng Liu, Dali Liu, Jessica Momb, Pei W. Thomas, Ashley Lajoie, Gregory A. Petsko, Walt Fast, and Dagmar Ringe, A Distal Phenylalanine Clamp Controls Substrate Specificity in the Quorum-Quenching Metallo-g-lactonase (AiiA) from Bacillus thuringiensis, Biochemistry, (2013) 52(9), 1603-1610
- Misty L. Kuhn, Salette Martinez, Natalie Gumataotao, Uwe Bornscheuer, Dali Liu*, Richard C. Holz* The Fe-Type Nitrile Hydratase from Comamonas testosteroni Ni1 Does Not Require an Activator Accessory Protein for Expression in Escherichia coli, Biochem. Biophys. Res. Commun., (2012) 424(3): 365-370
- Pei Thomas, Min Zheng, Shanshan Wu, Hua Guo, Dali Liu*, Dingguo Xu*, Walter Fast*, Characterization of Purified New Delhi Metallo-β-Lactamase-1 (NDM-1), Biochemistry, (2011) 50(46), 10102-10113.