Adjunct Full Professor

Cannon Research Center

Email:

Education:

• MD, Shanghai Second Medical University, China.
• Msc in Medical Science, Shanghai Medical University, Shanghai, China.
• PhD, University of London, England.

Professional Experience:

• Pathologist, Department of Pathology, Shanghai Medical University, Shanghai, China1974-1982
• Consultant, Department of Pathology, Shanghai Medical University, Shanghai, China, 1986-1988
• Research Fellow, Histopathology Unit, Imperial Cancer Research Fund, UK, 1993-1994
• Research fellow, Department of Histopathology, Royal Postgraduate Medical School, London, 1995-1996.
• Investigative Scientist, MRC CSC, Hammersmith Hospital, London, UK, 1996-2004
• Director, Senior Scientist, McColl Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Neuromuscular/ALS Center, Carolinas Medical Center, NC, USA, 2004-present

Research Interests:

• Antisense therapy for muscular dystrophy. Duchenne muscular dystrophy (DMD) is the most common devastating childhood muscuylar dystrophy and characterized by muscle weakness and wasting, which become clinically evident between the ages of 3 to 5 years. The underlying cause of the disease is the frame-shift mutations of the dystrophin gene. Antisense therapy for DMD aims to restore the reading-frame by removal of one or more exons next to the mutation break-point, or containing nonsense mutation. The therapy is therefore also called exon skipping therapy. Our lab is at the forefront of this new and exciting development. Currently, different chemistries and modification are being developed and tested for long-term efficacy. New methods are being established for the screening of effective oligonucleotide sequences targeting individual dystrophin exons for clinic application. Effective dose and treatment regiment are also being actively examined as preparation for clinic trials of systemic treatment to DMD. Interests also include collaborations to apply the antisense technique for treating other diseases.
• Non-viral gene delivery. Gene therapy for muscular dystrophies relies on the delivery of a normal copy of the disease gene into affected muscles. Gene delivery can be achieved through viruses or non-viral methods. Virus-mediated delivery is effective, but its safety remains to be tested. Non viral delivery is expected to be much safer, but despite tremendous efforts to translate the potentials of non-viral gene therapy to clinics, effective gene delivery into target cells, or muscles has been difficult. One biggest huddle for effective delivery of genes into muscles in vivo is that no reliable test system has been established in cell culture to indicate the potential of individual polymers or particles when they are used in animal models. My Interest has been focusing on synthesis of new polymers with potential for the delivery of oligonucelotides and transgenes in vivo. We are also testing cell culture systems to identify factors related to effective gene/oligomer delivery in vivo. Several classes of polymers have been synthesized and effective delivery has been achieved. Current studies aim to understand the interaction between therapeutic genes and the serum components, and to formulate polymer with plasmid/oligomers for enhanced delivery in vivo.

Publications:

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 Mar 10.

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 Mar 13.

Yokota T, Takeda S, Lu QL, Partridge TA, Nakamura A, Hoffman EP. A renaissance for antisense oligonucleotide drugs in neurology: exon skipping breaks new ground. Arch Neurol. 2009 Jan;66(1):32-8

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 restores cardiac functions in dystrophin-deficient mice by a morpholino oligomer. Pro. Nat. Acad. Sci. USA. 2008, Sep 30. online.

Doran T., Lu PJ., Vanier GS., Collins MJ., Wu B. & Lu QL. Microwave irradiation enhances gene and oligonucleotide delivery and induces effective exon skipping in myoblasts. Gene Ther. 2008, Sep 11. on line.

Elizabeth Keramaris-Vrantsis, Pei J. Lu, Timothy Doran, Allen Zillmer, Jignya Ashar, Christopher T. Esapa, Matthew A. Benson, Derek J. Blake, Jeffrey Rosenfeld and Qi L. Lu. Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mis-localization in muscle in vivo. Muscle & Nerve 2007 Oct;36(4):455-65.

Yokota T, Lu Q, Morgon JE, Davies KE, Fisher S, Tekada S, Partridge T, Expansion of revertant fibers in dystrophic mdx muscles reflects activity of muscle precursor cells and serves as an index of muscle regeneration. J Cell Sci. 2006,119:2679-87.

Alter L., Lou F., Rabinowitz A., Yin H-F., Rosenfeld J., Wilton S., Partridge T., Lu Q.L. Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nature Medicine. 2006 12 (2): 175-177.

Yun-Chao Chen, Hai-Dong Liang, Qing-Ping Zhang, Martin JK Blomley, Lu Q. L. Pluronic block copolymers: novel functions in ultrasound-mediated gene transfer and against cell damage. Ultrasound in Medicine and Biology. Ultrasound Med Biol. 2006 Jan;32(1):131-7.

Lu Q. L., Rabinowitz A., Chen Y. C., Toshifumi Y., Yin H. F., Alter J., Jadoon A., Bou-Gharios G. and Partridge T. Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. On line Early publication Proc. Natl. Acad. Sci. USA, 2005 4;102:198-203.

Liang H. D., Lu Q. L., Xue S. A., Halliwell M., Kodama T., Cosgrove D. O., Stauss H. J., Partridge T. A., Blomley M. J. Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells.
Ultrasound Med Biol. 2004 Nov;30(11):1523-9

Ponticos M., Abraham D., Alexakis C., Lu Q. L., Black C., Partridge T., Bou-Gharios G. Col1a2 enhancer regulates collagen activity during development and in adult tissue repair. Matrix Biol. 2004 Feb;22(8):619-28.

Lu Qi and Terence A. Partridge Antisense therapy corrects nonsense mutation by exon skipping. Discovery Medicine, 2003, 3(19):39-44

Lu Q. L, Christopher J. Mann , Fang Lou , Georges Bou-Gharios, Glenn E. Morris, Shao-an Xue, Sue Fletcher, Terence A. Partridge & Stephen D. Wilton^. Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nature Medicine 2003, 9:1009-1015

Lu, Q.L., Bou-Gharios, G. & Partridge, T.A. Non-viral gene delivery in skeletal muscle: a protein factory. Gene Ther. 10, 2003:131-142

Lu, Q.L., Liang, H.D., Partridge, T., & Blomley, M.J. Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage. Gene Ther. 10, 2003:396-405.

Shao-An Xue, Qi-Long Lu, J. M. Middeldorp, and Beverly E. Griffin Genetic Diversity: Frameshift Mechanisms Alter Coding of a Gene (Epstein-Barr Virus LF3 Gene) That Contains Multiple 102-Base-Pair Direct Sequence Repeats. Mol. Cellul. Biol. Mar. . 23( 6), 2003:2192–2201

Wells KE, Torelli S, Lu QL, Brown SC, Partridge T, Muntoni F, Wells DJ. Relocalization of neuronal nitric oxide synthase (nNOS) as a marker for complete restoration of the dystrophin associated protein complex in skeletal muscle. Neuromuscul Disord 2003 Jan;13(1):21-31

Wang Q, Holmes DI, Powell SM, Lu QL, Waxman J. Analysis of stromal-epithelial interactions in prostate cancer identifies PTPCAAX2 as a potential oncogene. Cancer Lett. 2002 Jan 10;175(1):63-69.

Crawford GE, Lu QL, Partridge TA, Chamberlain JS. Suppression of revertant fibers in mdx mice by expression of a functional dystrophin. Hum Mol Genet. 2001 Nov 15;10(24):2745-2750.

Xue SA, Lu QL, Poulsom R, Karran L, Jones MD, Griffin BE. Expression of two related viral early genes in Epstein-Barr virus-associated tumors. J Virol. 2000 Mar;74(6):2793-803

Lu QL, GE. Morris, SD. Wilton, T. Ly, OV. Artem’yeva, P. Strong and TA. Partridge. Massive Idiosyncratic Exon Skipping Corrects The Nonsense Mutation In Dystrophic Mouse Muscle And Produces Functional Revertant Fibres By Clonal Expansion. J Cell Biol. 2000; 148(5):985-995

Morrison J, Lu QL, Pastoret C, Partridge T and Bou-Gharios G. T-cell- dependent fibrosis in the mdx dystrophic mouse. Lab. Invest. 2000; 80