Dominic J Wells

Dominic J Wells

Professional background

I am a registered veterinary surgeon who qualified from Cambridge University in 1984. After several years in general practice I moved to the USA and did my PhD on hummingbird flight. After that I returned to the UK in 1990 with a lecturer post at the Royal Veterinary College (RVC) where I first became involved in DMD research. From 1995 to 2009 I worked at Imperial College London and becoming Professor in 2005. In January 2010 I returned to the RVC.

My research over the last 20 years has focussed on methods of somatic gene transfer with particular emphasis on DMD and the generation and analysis of genetically modified mice.

Work related to the exon skipping project

My laboratory is examining the factors influencing the efficiency of local and systemic administration of antisense phosphorodiaminate morpholino oligomers (PMO) in the mdx mouse model of DMD. We not only assess dystrophin expression by RT-PCR, western blots and immunostaining but also are fully equipped to assess in vivo and in vitro muscle function. Current results show that the number of dystrophin positive fibres is the most important determinant of the restoration of normal physiology.

Previous studies of systemic delivery have shown a lack of exon skipping and consequently no production of dystrophin in the heart. By combining microbubbles with diagnostic ultrasound we have shown that PMOs can be efficiently delivered to the mdx heart.

Relevant references

1. Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, Guglieri M, Ashton E, Abbs S, Nihoyannopoulos P, Garralda ME, Rutherford M, McCulley C, Popplewell L, Graham IR, Dickson G, Wood MJ, Wells DJ, Wilton SD, Kole R, Straub V, Bushby K, Sewry C, Morgan JE, Muntoni F (2009) Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 8(10):918-28

2. Alter, J., Sennoga, C.A., Lopes, D., Eckserley, R.J., Wells, D.J. (2009) Microbubble stability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transfer. Ultrasound in Medicine and Biology 35(6):976-84.

3. Muntoni F and D.J. Wells (2007) Genetic treatments in muscular dystrophy. Current Opinions in Neurology 20:590–594.

4. Wells, D.J. (2006) Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophy. Journal of Muscle Research and Cell Motility 27:387-398.

5. Wells, D.J. and K.E. Wells (2005). What do animal models have to tell us regarding Duchenne Muscular Dystrophy? Acta Myologica. 24: 172-180. 

6. Wells K.E., Fletcher, S., Mann, C.J., Wilton, S.D. and Wells, D.J. (2003) Enhanced in vivo delivery of antisense oligonucleotide to restore dystrophin expression in adult mdx mouse muscle. FEBS Lett. 552:145-149.

Links

Contact details:

Professor Dominic J Wells, MA VetMB PhD MRCVS

Neuromuscular Disease Group.

Department of Veterinary Basic Sciences

Royal Veterinary College, Camden campus

Royal College Street

London NW1 0TU, U.K.

Tel: +44 (0)20 3214 8024

E-mail: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

 
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