McColl Lockwood Laboratory for Muscular Dystrophy Research develops experimental therapies for the treatment of muscular dystrophies and to facilitate the translation of experimental therapies to clinical trials for improving the quality of life for patients with the disease.
The McColl-Lockwood Laboratory for Muscular Dystrophy Research, directed by Qi Long Lu, MD, PhD, is part of the Neuromuscular/ALS Center in the Department of Neurology, which provides service to patients in the Charlotte region and beyond. The Laboratory, located in the James G. Cannon Research Center, is funded with the support from the Carolinas Muscular Dystrophy Research Endowment, which was created by the McColl and Lockwood families, additional funding is from the Carolinas HealthCare Foundation as well as federally funded grants. The McColl-Lockwood Laboratory has continued to make milestone achievements in the field due to its research team of scientists and technicians with specialized training and experience in drug design, pharmacology, cell and molecular biology. The Laboratory has an academic association to the University of North Carolina both at Charlotte and Chapel Hill. The Laboratory also trains postgraduates and other students and is comprised of more than 2,000 square feet of space with state-of-the-art equipment which enables the researchers to focus on cell biology, molecular biology, drug development and drug tests both in vitro and in vivo.
The McColl-Lockwood Laboratory for Muscular Dystrophy Research focuses on developing novel therapies for muscular dystrophy, specifically limb-girdle muscular dystrophy (LGMD) and Duchenne muscular dystrophy (DMD). These diseases are caused by genetic defects (mutations) that disrupt normal muscle functions, resulting in weakening of muscle strength with fatal consequences. Currently, there is no cure or effective treatment for LGMD and DMD. The overriding goal of the Laboratory is to develop novel therapeutic approaches for the treatment of the diseases. The following are the main programs undertaken currently by the scientists in the McColl-Lockwood laboratory.
Significant progress made by the McColl-Lockwood Laboratory in the last few years is the result of strong support from the Carolinas Muscular Dystrophy Research Endowment and Cannon Research Center. Effective collaborations between many world renowned laboratories with research focuses on muscular dystrophies speed up the progress in searching for effective therapeutics for muscular dystrophies. The institutes include, but are not limited to the following: Children's National Medical Center, Washington DC; University of North Carolina, Chapel Hill; University of Iowa; University of Oxford UK; Cardiff University, UK; National Institute of Neuroscience, Tokyo, Japan.
Selected Recent Publications
Awano H, Blaeser A, Keramaris E, Xu L, Tucker J, Wu B, Lu P, Lu QL. Restoration of functional glycosulation of a-dystroglycan in FKRP mutant mice is associated with muscle regeneration. Am J Pathol. 2015 May 11. PMID: 25976249
Wu B, Cloer C, Lu P, Milazi S, Shaban M, Shah S, Marston-Poe L, Moulton HM, Lu QL. Exon skipping restores dystrophin expression, but fails to prevent disease progression in later stage dystrophic Dko mice. Gene Ther. 2014;21(9):785–93. PMCID: PMC4167372
Wang M, Wu B, Lu P, Tucker JD, Milazi S, Shah SN, Lu QL. Pluronic-PEI copolymers enhance exon-skipping of 2'-O-methyl phosphorothioate oligonucleotide in cell culture and dystrophic mdx mice. Gene Ther. 2014 Jan; 21(1):52-9. PMID 24131982
Vannoy CH, Xu L, Keramaris E, Lu P, Xiao X, Lu QL. AAV-mediated overexpression of LARGE rescues α-dystroglycan function in dystrophic mice with mutations in the fukutin-related protein. Hum Gene Ther Methods. 2014; 25(3):187-96. PMID 24635668
Lu QL, Cirak S, Partridge T. What can we learn from clinical trials of exon skipping for DMD? Mol Ther Nucleic Acids. 2014 Mar 11; 3:e152. Full Text
Xu L, Lu PJ, Wang CH, Keramaris E, Qiao C, Xiao B, Blake DJ, Xiao X, Lu QL. Adeno-associated Virus 9 Mediated FKRP Gene Therapy Restores Functional Glycosylation of α-dystroglycan and Improves Muscle Functions. Mol Ther. 2013;21(10):1832-40. PMID 23817215.
Wang M, Wu B, Lu P, Cloer C, Tucker JD, Lu QL. Polyethylenimine-modified pluronics (PCMs) improve morpholino oligomer delivery in cell culture and dystrophic mdx mice. Mol Ther. 2013;Jan;21(1):210-6. [PMID 23164938]
Xu L, Lu PJ, Wang CH, Keramaris E, Qiao C, Xiao B, Blake DJ, Xiao X, Lu QL. Adeno-associated virus 9 mediated FKRP gene therapy restores functional glycosylation of α-dystroglycan and improves muscle functions. Mol Ther. 2013, Oct;21(10):1832-1840. [PMID 23817215]
Blaeser A, Keramaris E, ChanYM, Sparks S, Cowley D, Xiao X, Lu QL. Mouse models of Fukutin-related protein mutations show a wide range of disease phenotypes. Hum Genet, 2013 Aug;132(8):923-934. [PMID 23591631]
Wu B, Lu P, Cloer C, Shaban M, Grewak S, Milazi S, Shah SN, Moulton HM, Lu QL. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino. Am J Pathol. 2012, Aug;18(2);392-400. [PMID 22683468]
Hu Y, Wu B, Zillmer A, Lu P, Benrashid E, Wang M, Doran T, Shaban M, Wu X, Lu QL. Guanine analogues enhance antisense oligonucleotide-induced exon skipping in dystrophin gene in vitro and in vivo. Mol Ther 2010;18:812-8 [PMID: 20087314]
Chan YM, Keramaris-Vrantsis E, Lidov H, Norton JH, Zinchenko N, Gruber HE, Thresher R, Blake DJ, Ashar J, & Lu QL. Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies. Hum Mol Genet 2010 Aug 11. [PMID: 20675713]
Moulton HM, Wu B, Jearawiriyapaisarn N, Sazani P, Lu QL, Kole R. Peptide-morpholino conjugate: a promising therapeutic for Duchenne muscular dystrophy. Ann N Y Acad Sci 2009;1175:55-60. [PMID: 19796077]
Wu B, Lu P, Benrashid E, Malik S, Ashar J, Doran TJ, Lu QL. Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino. Gene Ther 2010;17:132-40. [PMID: 19759562]
Lu PJ, Zillmer A, Wu X, Lochmuller H, Vachris J, Blake D, Chan YM, Lu QL. Mutations alter secretion of fukutin-related protein. Biochim Biophys Acta 2010;1802:253-8. [PMID: 19900540]
Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs. Ann Neurol 2009;65:667-76. [PMID: 19288467]
Wu B, Li Y, Morcos PA, Doran TJ, Lu P, Lu QL. Octa-guanidine Morpholino Restores Dystrophin Expression in Cardiac and Skeletal Muscles and Ameliorates Pathology in Dystrophic mdx Mice. Mol Ther 2009;17:864-71. [PMID: 19277018]
Wu B, Moulton HM, Iversen PL, Jiang J, Li J, Li JB, Spurney CF, Sali A, Guerron AD, Nagaraju K, Doran T, Lu PJ, Xiao X & Lu QL. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci USA 2008;105:14814-9. [PMID: 18806224]
Lu QL, Wu B. Systemic delivery of antisense oligomer in animal models and its implications for treating DMD. Methods Mol Biol. 2012;867:393-405. [PMID 22454075]
Qi Lu, MD, PhD, Director
Anthony Blaeser, PhD, Postdoctoral Research Fellow
Lauren Bollinger, Research Technician
Alison Long, Research Technician
Pei Lu, Laboratory Supervisor
Jason Tucker, PhD, Postdoctoral Research Fellow
Charles Vannoy, PhD, Postdoctoral Research Fellow
Bo Wu, PhD, Research Scientist
Mingxing Wang, PhD, Research Scientist
Caren Anderson, Program Coordinator