Back to Main

Faculty Detail     Name MING LUO   Campus Address CBSE 111 Zip 4400 Phone 205-934-4259 E-mail mingluo@uab.edu Other websites

Education Undergraduate  Wuhan University    1982  B.S.  Graduate  Purdue University    1987  Ph.D.

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Microbiology  Microbiology Professor Secondary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Pathology   Cell Adhesion & Matrix Research Center Professor Center  Center for AIDS Research  Center for AIDS Research Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations Biochemistry and Molecular Genetics Program  Cellular and Molecular Biology Program  Microbiology

Biographical Sketch  Ming Luo, Professor, received his Bachelor's Degree in Science from the Department of Chemistry, Wuhan University, China in 1982. His graduate work was to determine the three-dimensional structure of spherical viruses by X-ray crystallography. He completed his Ph.D. studies at the Department of Biological Sciences, Purdue University in 1987. His work on the Mengo virus structure established a novel approach to structure determination of spherical viruses. After he received his PhD in 1987, he joined the faculty of UAB in the department of microbiology in the same year and rose to full professor in 1996. His work on Theiler’s virus revealed how the virus was assembled, and its homology to other picornaviruses. We showed that sialic acid is a receptor moiety that regulates the persistent infection of Theiler’s virus and may explain how it relates to its disease pattern as the model for multiple sclerosis. He also worked on the matrix protein (M1), NS2, and neuraminidase of influenza virus, and developed neuraminidase inhibitors that are now marketed as antiviral drugs. He played a key role in developing the structural genomics pipeline for solving structures from C. elegans genome. He solved crystal structures of proteins from vesicular stomatitis virus (VSV) and worked on the cryoEM structure of VSV particle.

Research/Clinical Interest Title Structure-Based Approaches to Anti-Infectious Agents Description Infectious diseases are identified as the third major cause of death in the United States. Development of effective and economic therapy of infectious diseases requires thorough understanding of the biology of these infectious agents and innovative approaches to the problems. My laboratory has been involved in X-ray crystallographic analysis of critical proteins and design of novel drugs based on the protein structure. Influenza virus neuraminidase - Influenza virus remains to be a major causative agent for a large number of death among elderly people and young children, and huge economic losses due to illness. Influenza virus is an enveloped virus containing negative strand segmented genomic RNA's. On the viral membrane surface, there are two major antigens, haemagglutinin and neuraminidase. We have been working on the three-dimensional structure of neuraminidase, a tetrameric glycoprotein of 240,000 daltons. Based on the structural information, we started to design new inhibitors which should have a potential to be developed as antiviral drugs. The process of inhibitor design involves modeling potential inhibitors using the active site structure and several computer programs; chemical synthesis of the designed inhibitors and testing these inhibitors for their efficacy; and determining the complex structure of new inhibitors and neuraminidase, which could suggest further modifications of the inhibitors. Today, a new series of inhibitors with a good inhibitory effect (best IC50<5x10-8m) has been designed and a patent application has been approved for these compounds. A novel pattern of interactions between NA and inhibitors was identified. This is the first time a noncarbohydrate inhibitor was ever designed to fit the active site of NA. The best compound was shown to inhibit influenza virus replication in cell culture and a mouse model system. we also expand the scope of drug design to include bacterial sialidases which are important virulent factors of bacterial pathogenesis. For instance, data showed that elevated sialidase activity in bacterial vaginosis patients is correlated to prematurity in pregnant women. Bacterial sialidase also plays a significant role in the unusual colonization of pseudomonas aeruginosa in cystic fibrosis patients. We suggest that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases. The structure of two bacterial sialidases has been determined and made available. We have designed and synthesized two inhibitors based on these structures. We should be able to further improve these inhibitors and test them for antimicrobial activities in vivo. Crystals of salmonella sialidase have been reproduced in my laboratory and are used for studying the inhibitor-enzyme complexes. The sialidase inhibitors can also be used to prevent trypanosome cruzi infection, the causative agent of chagas' disease because a trans-sialidase of t. cruzi, a very similar enzyme to bacterial sialidase, may also be inhibited by these inhibitors. Recently, we successfully solved the structure of the matrix protein M1 of influenza virus to 2.2 Å resolution. M1 is involved in transport and assembly of viral genomic RNA. The structure revealed the regions which mediate the interaction between the viral membrane and the RNA nucleocapsid. This will provide a new target for design of anti-influenza virus drugs. Other influenza proteins are also under study.

Selected Publications  Publication PUBMEDID Lin WJ, Zheng X, Lin CC, Tsao J, Zhu X, Cody JJ, Coleman JM, Gherzi R, Luo M, Townes TM, Parker JN, Chen CY. Post-transcriptional control of type I interferon genes by KSRP in the innate immune response against viral infection. Mol Cell Biol. (16):3196-207. (2011).   21690298  Green TJ, Rowse M, Tsao J, Kang J, Ge P, Zhou ZH, Luo M. Access to RNA encapsidated in the nucleocapsid of vesicular stomatitis virus. J Virol. (6):2714-2., (2011).  21177817  Ge P, Tsao J, Schein S, Green TJ, Luo M, Zhou ZH. Cryo-EM model of the bullet-shaped vesicular stomatitis virus. Science, 327(5966):689-93. (2010).  20133572  Green TJ, Luo M. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P. Proc Natl Acad Sci, 106(28):11713-8. (2009).  19571006  Brandes M, Willimann K, Bioley G, Lévy N, Eberl M, Luo M, Tampé R, Lévy F, Romero P, Moser B. Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell responses. Proc Natl Acad Sci U S A. 106(7):2307-12. (2009).  19171897  Green TJ, Zhang X, Wertz GW, Luo M. “Structure of the vesicular stomatitis virus nucleoprotein-RNA complex”. Science, 313(5785):357-60. (2006).  16778022  Lommer, B. S. and M. Luo. "Structural Plasticity in influenza virus protein NS2 (NEP)". J. Biol. Chem. 277:7108-7117. (2002).   11751904  Sha, B.D., S.E., Phillips, V.A. Bankitas, and M. Luo. “Crystal Structure of the Saccharomyces cerevisiae phosphatidylinositol transfer protein”. Nature, 391:506-510. (1998).   9461221  Sha, B.D. and Luo, M. “The Crystal Structure of a Bifunctional Membrane-RNA Binding Protein, Influenza Virus Matrix Protein”, Nature Structural Biology, 4:239-244. (1997).   9164466  Jedrzejas, M. J., Singh, S., Brouillette, W., Air, M.G., Laver, W.G. and Luo, M. "Structure of Aromatic Inhibitors of Influenza Virus Neuraminidase", Biochemistry, 34:3144-3151. (1995).   7880809  First Prev   1 2 of  2  Next Last

Keywords Virus structure, antiviral drugs, X-ray crystallography

© 2008 University of Alabama at Birmingham. All rights reserved. DisclaimerAbout this SiteGraphic Design Created by UAB Web Communications.
Calendar Designed by Medical Education Information Services. To report problems with the site, email us at meis@uab.edu. Last Revision: February 15, 2012.
The UAB School of Medicine Mailing Address: 1530 3rd Avenue South, FOT 1203, Birmingham AL 35294-3412