Prior Positions and Experience

1997-2004	Research Scientist, Clinical Science Centre, MRC (London, UK)
1992-1996	Research Fellow, Royal Postgraduate Medical School (London, UK)
1978-1982	Consultant in Pathology, Shanghai Medical University (Shanghai, China)

Education

PhD: 1991, University of London (London, UK)
MS: 1986, Shanghai Medical University (Shanghai, China)
MD: 1976, Shanghai Second Medical University (Shanghai, China)

Development of Therapies for Muscular Dystrophies

Dr. Lu’s main interests are gene therapy, oligonucleotide therapy and read-through strategy for muscular dystrophies with a goal to treat limb-girdle muscular dystrophy (LGMD) type 2I.

Gene therapy uses a normal copy of gene to replace the defected disease gene. Success of the therapy for muscular dystrophies relies on the delivery of a normal copy of the gene into diseased muscles. Gene delivery can be achieved by viruses or non-viral methods. Despite tremendous efforts to translate the potentials of non-viral gene therapy to clinics, effective gene delivery into target cells has been elusive. We have experimented several physical (electroporation, ultrasound) and chemical methods (pluronic polymers and microbubbles) to enhance gene delivery into muscle. Currently, natural and synthetic polymers are being examined and significant progress has been made for enhanced delivery of transgenes in both cell culture and animal models in vivo.

Another ongoing project is to use antisense oligonucleotides therapy to target specific sequences (called exons) of the human dystrophin gene. This removes the defective part of the dystrophin gene and restores the expression of dystrophin protein, which is missing in the DMD patients. In 2003, we first demonstrated the therapeutic potential of antisense therapy for DMD. Since then, significant progress has been made. We are now able to restore the dystrophin expression in muscles throughout the body by systemic delivery of antisense oligomers. Long-term maintenance of dystrophin expression and functional improvement of muscles can also be achieved. Our ongoing efforts aim to establish specific oligomers for targeting human dystrophin exons and optimal regimens for clinic trials.

Drug-mediated read-through strategy to bypass stop codons has the potential to treat a sub-set of DMD and LGMD patients carrying nonsense mutations. Currently, the McColl-Lockwood Laboratory has established a cell culture system for screening drugs to enhance the read-through mechanism. Preliminary results have demonstrated the potential of a small group of drugs with the expected read-through activity.

Recent Publications

Keramaris-Vrantsis E, Lu PJ, Doran T, Zillmer A, Ashar J, Esapa CT, Benson MA, Blake DJ, Rosenfeld J, Lu QL. Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. Muscle Nerve 2007; 36: 455-465. [PMID: 17554798] 

Alter J, Lou F, Rabinowitz A, Yin H, Rosenfeld J, Wilton SD, Partridge TA, Lu QL. Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat Med 2006; 12:175-177. [PMID: 16444267]

Lu QL, Mann CJ, Lou F, Bou-Gharios G, Morris GE, Xue SA, Fletcher S, Partridge TA, Wilton SD. Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse.Nat Med 2003; 9:1009-1014.  [PMID: 12847521]

Lu QL, Bou-Gharios G, Partridge TA.Non-viral gene delivery in skeletal muscle: a protein factory. Gene Ther 2003; 10: 131-142. [PMID: 12571642]

Current, Recent and Pending Grant Support

Grant Title: Morpholino antisense oligonucleotide and systemic delivery
Funding Agency: Department of Defense (USAMRMC)
Role: Principal Investigator
Years: 2006-2009

Grant Title: Polymer for gene delivery
Funding Agency: North Carolina Biotechnologies
Role: Principal Investigator
Years: 2007-2008

Grant Title: Exon 50 skipping for treatment of Duchenne muscular dystrophy
Funding Agency: Charlie’s Fund
Role: Principal Investigator
Years: 2005-2007

Grant Title: Systemic delivery of antisense oligonucleotides for the treatment of DMD
Funding Agency: Muscular Dystrophy Association
Role: Principal Investigator
Years: 2005-2006