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Xiaohua Wu

Xiaohua Wu, MD, PhDXiaohua Wu, MD, PhD
Research Faculty, Drug Discovery Group
McColl-Lockwood Laboratory for Muscular Dystrophy Research
Department of Neurology

Prior Positions and Experience

2005-2006 Assistant Project Scientist, Department of Pathology,UCSD School of Medicine (La Jolla, Calif.)
2000-2005 Research Associate, Glycobiology Program, The Burnham Institute (La Jolla, Calif.)
1998-2000 Postdoctoral Fellow, Department of Pathology, St. Jude Children’s Research Hospital (Memphis, Tenn.)
1997 Visiting Scientist, Max-Planck Institute for Plant Breeding Research (Cologne, Germany)
1986-1990 Radiologist, Changsha Hospital (Changsha, China)

Education

PhD: 1996, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (Shanghai, China)
MS: 1993, Shanghai Institute of Nuclear Research Chinese Academy of Sciences (Shanghai, China)
MD: 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 asFukuyama 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.

Recent Publications

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]

Wu X, Freeze HH. GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative splice forms. Genomics 2002; 80: 553-557. [PMID: 12504846]

Current, Recent and Pending Grant Support

Grant Title: Drug discovery for muscular dystrophy from natural products
Funding Agency:North Carolinas Biotechnology Center, Biotechnology Research Grant
Role: Principal Investigator
Years: 2009-2011

GrantTitle: HTS Assay for Enhancer of Glycosylation of Dystroglycan
Funding Agency: NIH
Role: Principal Investigator
Years: 2009-2011

Grant Title: Enhancing Laminin Functional Binding to Treat Muscular Dystrophies
Funding Agency: Muscular Dystrophy Association Research Grant (Pending)
Role: Principal Investigator
Years: 2010-2012

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