Prior Positions and Experience
Assistant Project Scientist, Department of Pathology,UCSD School of Medicine (La Jolla, Calif.)
Research Associate, Glycobiology Program, The Burnham Institute (La Jolla, Calif.)
Postdoctoral Fellow, Department of Pathology, St. Jude Children’s Research Hospital (Memphis, Tenn.)
Visiting Scientist, Max-Planck Institute for Plant Breeding Research (Cologne, Germany)
Radiologist, Changsha Hospital (Changsha, China)
1996, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (Shanghai, China)
1993, Shanghai Institute of Nuclear Research Chinese Academy of Sciences (Shanghai, China)
1986, Hunan University of Traditional Chinese Medicine (Changsha, China)
Drug Discovery for Muscular Dystrophies
Dr. Wu has long-standing research interests in elucidating the mechanisms of hypoglycosylation-related diseases. A large number of human diseases are associated with hypoglycosylation of proteins including a group of muscular dystrophies (MD) such as Fukuyama congenital muscular dystrophy (FCMD), muscle-eyes-brain disease (MEB) and limb-girdle muscular dystrophy type 2I (LGMD2I). In these diseases, the glycosylation of dystroglycan (α-DG) is compromised due to mutations in the genes involved in protein O-mannosylation pathway, such as Fukutin, FKRP, LARGE, POMGnT1, and POMT1. Defects in these genes cause hypoglycosylation of α-DG and result in severe clinical manifestation. There is no effective therapy available for any form of MD. Emerging evidence indicates that overexpression of glycosyltransferase in muscle can rescue several forms of MD in mouse models. Thus, up-regulation of glycosylation pathways to enhance α-DG glycosylation in muscle becomes a novel avenue for therapies for MD. Dr. Wu’s group postulates that up-regulation of glycosylation pathways by small compounds would enhance glycosylation of α-DG and restore the functions of α-DG to rescue hypoglycosylation-related and perhaps other forms of MD. The major goal for this group is to discover drugs for treating hypoglycosylation related muscular dystrophies.
Current projects: 1) Drug discovery for muscular dystrophies. The group has developed a cell-based assay for high throughput screening of small compound libraries. The goal for this project is to discover small compound drugs for MD. Several lead compounds have been identified and the validation of those compounds in MD mouse models is in process. Dr Wu is also interested in purification and identification of natural products from variety of resources to accelerate the drug discovery project. 2) The roles of hypoglycosylation of proteins in human diseases (Glycopathology). Dr Wu is searching for disease associated glycans as biomarkers for drug discovery targets and disease diagnosis.
Gaultier A*, Wu X*, Le Moan N, Takimoto S, Mukandala G, Akassoglou K, Campana WM, Gonias SL. (2009) Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis. J Cell Sci. 2009 Apr 15; 122 (Pt 8): 1155-62. [PMID: 19299462]
Wu X, Li ZF, Brooks R, Komives EA, Torpey JW, Engvall E, Gonias SL, Shelton GD. Autoantibodies in canine masticatory muscle myositis recognize a novel myosin binding protein-C family member. J Immunol 2007; 179: 4939-4944. [PMID: 17878394]
Wu X, Steet RA, Bohorov O, Bakker J, Newell J, Krieger M, Spaapen L, Kornfeld S, Freeze HH. Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. Nat Med 2004; 10: 518-523. [PMID: 15107842]
Wu X, Rush JS, Karaoglu D, Krasnewich D, Lubinsky MS, Waechter CJ, Gilmore R, Freeze HH. Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij. Hum Mutat 2003; 22: 144-150. [PMID: 12872255]