Faculty & Staff
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
1. Wu, R.; Diez, M. D. A.; Figueroa, C. M.; Machtey, M.; Iglesias, A. A.; Ballicora, M. A.; Liu, D. L., The Crystal Structure of Nitrosomonas europaea Sucrose Synthase Reveals Critical Conformational Changes and Insights into Sucrose Metabolism in Prokaryotes. Journal of Bacteriology 2015, 197 (17), 2734-2746.
2. Mascarenhas, R.; Thomas, P. W.; Wu, C. X.; Nocek, B. P.; Hoang, Q. Q.; Liu, D. L.; Fast, W., Structural and Biochemical Characterization of AidC, a Quorum-Quenching Lactonase with Atypical Selectivity. Biochemistry 2015, 54 (28), 4342-4353.
3. Martinez, S.; Wu, R.; Krzywda, K.; Opalka, V.; Chan, H.; Liu, D. L.; Holz, R. C., Analyzing the catalytic role of active site residues in the Fe-type nitrile hydratase from Comamonas testosteroni Ni1. Journal of Biological Inorganic Chemistry 2015, 20 (5), 885-894.
4. Le, H. V.; Hawker, D. D.; Wu, R.; Doud, E.; Widom, J.; Sanishvili, R.; Liu, D. L.; Kelleher, N. L.; Silverman, R. B., Design and Mechanism of Tetrahydrothiophene-Based gamma-Aminobutyric Acid Aminotransferase Inactivators. Journal of the American Chemical Society 2015, 137 (13), 4525-4533.
5. Lee, H.; Doud, E. H.; Wu, R.; Sanishvili, R.; Juncosa, J. I.; Liu, D. L.; Kelleher, N. L.; Silverman, R. B., Mechanism of Inactivation of gamma-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115). Journal of the American Chemical Society 2015, 137 (7), 2628-2640.
6. Clevenger, K. D.; Wu, R.; Liu, D. L.; Fast, W., n-Alkylboronic Acid Inhibitors Reveal Determinants of Ligand Specificity in the Quorum-Quenching and Siderophore Biosynthetic Enzyme PvdQ. Biochemistry 2014, 53 (42), 6679-6686.
7. Liao, J. L.; Wu, C. X.; Burlak, C.; Zhang, S.; Sahm, H.; Wang, M.; Zhang, Z. Y.; Vogel, K. W.; Federici, M.; Riddle, S. M.; Nichols, R. J.; Liu, D. L.; Cookson, M. R.; Stone, T. A.; Hoang, Q. Q., Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain. Proceedings of the National Academy of Sciences of the United States of America 2014, 111 (11), 4055-4060.
8. Martinez, S.; Wu, R.; Sanishvili, R.; Liu, D. L.; Holz, R., The Active Site Sulfenic Acid Ligand in Nitrile Hydratases Can Function as a Nucleophile. Journal of the American Chemical Society 2014, 136 (4), 1186-1189.
9. Clevenger, K. D.; Wu, R.; Er, J. A. V.; Liu, D. L.; Fast, W., Rational Design of a Transition State Analogue with Picomolar Affinity for Pseudomonas aeruginosa PvdQ, a Siderophore Biosynthetic Enzyme. Acs Chemical Biology 2013, 8 (10), 2192-2200.
10. Li, S. Q.; Schenkel, M.; Drake, A.; Liu, D. L.; Novak, W. R. P., Novel inhibitors of acetate kinase from Francisella tularensis. Faseb Journal 2013, 27.
11. Liu, C. F.; Liu, D. L.; Momb, J.; Thomas, P. W.; Lajoie, A.; Petsko, G. A.; Fast, W.; Ringe, D., A Phenylalanine Clamp Controls Substrate Specificity in the Quorum-Quenching Metallo-gamma-lactonase from Bacillus thuringiensis. Biochemistry 2013, 52 (9), 1603-1610.
12. Kuhn, M. L.; Martinez, S.; Gumataotao, N.; Bornscheuer, U.; Liu, D. L.; Holz, R. C., The Fe-type nitrile hydratase from Comamonas testosteroni Ni1 does not require an activator accessory protein for expression in Escherichia coli. Biochemical and Biophysical Research Communications 2012, 424 (3), 365-370.
13. Thomas, P. W.; Zheng, M.; Wu, S. S.; Guo, H.; Liu, D. L.; Xu, D. G.; Fast, W., Characterization of Purified New Delhi Metallo-beta-lactamase-1. Biochemistry 2011, 50 (46), 10102-10113.
14. Drake, A. K.; Isaac, R. S.; Schenkel, M. J.; Wolfson, N.; Stancu, B. G.; Liu, D. L.; Novak, W. R. P., Structural and kinetic characterization of Francisella tularensis acetate kinase. Faseb Journal 2011, 25.