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Dr Lawrence Moon

Team

  • Dr Denise Duricki/Postdoc
  • Dr Barbara Haenzi/Postdoc
  • Claudia Kathe/PhD Student
  • Edward Fletcher/PhD Student
  • Christina Wayman/PhD Student
  • Dhireshan Gadiagellan/PhD Student

Translational goals

The long-term research goal for my laboratory is to identify strategies for promoting recovery after CNS injuries, including spinal cord injury and focal cerebral ischemia (stroke).

Stroke

Stroke (caused by a clot or a bleed) rapidly kills brain cells and disables millions worldwide. Stroke costs the EU €38 billion each year. New therapies are urgently needed: they must work in an elderly body (because >91% of EU stroke victims are >65 years old) and should work when treatment is initiated after many hours (because >50% of stroke victims are not diagnosed within six hours, and >31 million people have had strokes >1 month ago).

We are currently funded by a Starter/Consolidator grant from the European Research Council to evaluate a novel potential therapy for improving dexterity and locomotion in elderly rats. A former PhD student (and now postdoc) in my laboratory, Denise Duricki, identified the world’s first therapy for stroke which partially reverses arm disabilities in elderly rats after injection into upper arm muscles, even when administered 24 hours after stroke. This is ground-breaking because the therapy works 1) in elderly bodies 2) when given after 24 hours 3) by a clinically-straightforward route (muscle injection). 4) The therapy involves delivery of a human molecule which naturally occurs in muscle and has been proven safe and effective in clinical trials for other disorders. My team members Christina Wayman and Dhireshan Gadiagellan also work on this project, with specialties including neuroimaging (MRI) and behavioural testing. Our long-term goal is to determine whether this improves hand and arm function in elderly people after stroke when treated one or more days after stroke.

A former PhD student in my laboratory, Sara Soleman, showed that intraspinal injection of “chondroitinase ABC” improves sensory and motor function in elderly rats. This is important because the therapy works in an elderly nervous system even when the injections are made three days after stroke. This work was published in the journal “Brain”.

Spinal Cord Injury

Another goal of my team is to identify novel molecules (“regeneration-associated genes”; RAGs) that increase the re growth of nerve fibers after spinal cord injury, with a view to restoring sensory and motor function. I completed a postdoc in Prof. Mary Bartlett Bunge’s laboratory at the Miami Project to Cure Paralysis. There, we identified a novel set of >500 candidate RAGs using laser microdissection of spinal cord neurons that regenerated axons into a Schwann cell bridge in vivo. In the next stage, Tom Hutson (my former PhD student and postdoc), developed a medium throughput screen using primary neurons to identify which of these RAGs increase axon growth when overexpressed. The assay involves 96 well electroporation with automated microscopy and neurite growth measurement. Tom identified more than 20 lead “hits”.

1Moon

He is now exploring two of our lead hits in detail together with Claudia Kathe using various in vivo models of rat spinal cord injury. To do this we use bicistronic adeno-associated viral vectors for overexpression of RAGs together with a fluorescent reporter gene.

Claudia has also developed several methods for assessing functional recovery after spinal cord injury including new methods that involve neural stimulation and recording after delivery of novel potential therapies for spinal cord injury.

Barbara Haenzi is a postdoc with her own fellowship from  the Swiss National Foundation. She has expertise in cancer and kidney function and a special interesting in signalling downstream of the Fibroblast Growth Factor receptor. She is now studying various pro-regenerative genes that Tom identified, including FGF receptor 1.

Ed Fletcher is a PhD student with a Health Schools studentship who is co-supervised by Dr Susan Duty. His PhD relates to improving outcome in rodent models of Parkinson’s Disease by modulation of extracellular matrix molecules and/or by enhancement of neuroplasticity in the basal ganglia.

This neuroplasticity research is exciting because these are entirely novel candidate targets for repair of CNS disease and injury. The next step will be to test these novel hits in animal models to determine whether these are effective therapeutic targets of restoring lost sensory and/or motor function. This work was conducted in collaboration with Profs. John Bixby, Vance Lemmon and Prof. Mary Bunge.

Academic roles

I’m a Senior Lecturer in the Department of Pharmacology. I particularly enjoy teaching in the laboratory and we train BSc and MSc students every year. With Dr. Aileen King, I co-ordinate the “Animal Models of Disease and Injury” course for BSc students. I also teach on various Neuroscience courses and run several practical classes and workshops throughout the year. I have a special interest in Experimental Design and Statistical Analysis, and prefer a method based on real case studies for teaching this subject so as not to alienate students!

Publications

PDFs are downloadable from

www.lawrencemoon.co.uk/publications

Funding

• European Research Council

• International Spinal Research Trust

• Rosetrees Trust

• Wings for Life Charity

Previous Funding

• British Pharmacological Society’s Integrative Pharmacology Fund

• Medical Research Council

• BBSRC

• Dunhill Medical Trust

• Dowager Countess Eleanor Peel Trust

• Henry Smith Charity

• Royal Society

• Christopher and Dana Reeve Paralysis Foundation

• University of London’s Central Research Fund.

Autobiography

Lawrence Moon graduated from University of Oxford in 1997 with the top First BA (Joint Hons.) in Physiology, Psychology and Philosophy. He obtained a PhD from the University of Cambridge in 2001, investigating methods for promoting regeneration of injured axons in the adult rat nigrostriatal system. Some of the work from his PhD was published in Nature Neuroscience: this identified chondroitinase ABC as a method for promoting re-growth of injured nerve fibers. Subsequent collaboration with Dr Liz Bradbury and Prof. Steve McMahon at King’s College London led to a publication in Nature: their work showed that chondroitinase ABC improves sensory and motor function after spinal cord injury in rats.

In 2001 he moved to the Miami Project to Cure Paralysis at the University of Miami, FL, USA, where he worked in the lab of Prof. Mary Bartlett Bunge. He was also an Associate member of the Christopher and Dana Reeve Foundation’s International Research Consortium. Collaborative work led to publications in Nature Reviews Neuroscience.

In 2005, Dr Moon was awarded a Research Councils UK Academic Fellowship at King’s College London. This work was also funded by the British Pharmacological Society’s Integrative Pharmacology Fund.

In 2012, he was promoted to Senior Lecturer.

 

 

 

 

 

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