... / ... / ... / Principal Investigators / Alan Burns

Alan Burns

Dr. Alan J. Burns (PhD) Afbeelding
Department of Clinical Genetics
Erasmus MC
Faculty building
Wytemaweg 80
3015 CN Rotterdam
The Netherlands

Email: a.burns@erasmusmc.nl


Biosketch

Alan Burns studied for a PhD in developmental neurobiology at the University of Ulster in Northern Ireland. He then moved to the University of Nevada (Reno) in the US as a post-doctoral researcher in the laboratory of Profs. Kent Sanders and Sean Ward to investigate the role of interstitial cells of Cajal (ICC) in motility of the gastrointestinal tract. This resulted in seminal studies demonstrating that ICC are electrical pacemakers and mediators of neurotransmission within the gut. A second post-doctoral position in Prof. Nicole Le Douarin’s laboratory in Paris established his career on development of the enteric nervous system from neural crest-derived precursors. There followed a brief faculty appointment at the University of Ulster before moving to University College London (UCL) Institute of Child Health as senior lecturer and Principal Investigator in 2001, where his group is mainly based. In 2013 he was awarded an honorary appointment as associate professor in the Department of Clinical Genetics at the Erasmus MC.



Research activity

The overall aim of the research is to better understand, and establish novel treatments for, disorders/diseases resulting from abnormal development of the neuromuscular components of the gastrointestinal tract.
Normal gut contraction and function requires the coordinated interaction of the enteric neurons and glial cells that comprise the enteric nervous system (ENS), interstitial cells of Cajal, and smooth muscle cells. Defects in the development of these cell types results in a range of commonly occurring gut disorders/diseases including Hirschsprung disease (aganglionic megacolon), intestinal pseudo-obstruction, and other motility defects. 
The ENS, the intrinsic innervation of the gut, is entirely derived from neural crest cells (NCC). These precursors undergo extensive migration, proliferation and differentiation in order to colonise the entire length of the gut and form the ENS. Defects in these processes can result in the congenital disorder Hirschsprung disease (HSCR), where variable lengths of the hindgut remain aganglionic, resulting in tonic contraction of the aganglionic colon segment and functional obstruction. To date, 12 genes have been implicated in HSCR development, with RET being the most important. However, only approximately 20% of HSCR cases can be explained by mutations in these genes, supporting genetic heterogeneity for this disorder. Although HSCR is the best characterized pediatric enteric neuropathy, the genetic basis of other neuromuscular diseases affecting the gastrointestinal tract is less well understood, driving a need for research in this area.

We take a number of approaches, in collaboration with groups locally, nationally and internationally to:

  • investigate the molecular and genetic factors controlling enteric nervous system (ENS) formation from neural crest-derived precursors
  • determine, by functional analysis, whether candidate genes identified in enteric neuropathies and myopathies, are actually disease causing genes
  • develop novel stem cell-based therapies for aganglionic gut disorders such as HSCR
  • use tissue engineering approaches to manufacture replacements for diseased gut.
     


Key Words

Enteric nervous system, development, Hirschsprung disease, enteric neuropathies, neurogastroenterology, stem cell therapy, gut tissue engineering.



Current Grants

2016 Horizon 2020 “INtestinal Tissue ENgineering Solution (INTENS) for children with short bowel syndrome”. (Euros 1,000,700) Co-I 5 years.

2015 Great Ormond Street Hospital Children’s Charity “Development of a functional tissue engineered intestine”. (£135,204) Co-I 1 year.

2014 The Anatomical Society PhD Studentship. “Biology and therapeutic potential of enteric nervous system stem cells for spinal cord repair”. (£72,678) PI  3 years.

2014 Sophia Kinderziekenhuis Fonds 4 year PhD studentship. “Isolation, characterisation and genetic rescue of enteric nervous system stem cells for use as a novel therapy in Hirschsprung's disease”. (Euros 254,500) Co-PI 4 years.

2011 Great Ormond Street Hospital Children’s Charity, “Human enteric neural stem cells for cell therapy”. (£1,217,362) Co-I 5 years.



Publications

Binder, E., Natarajan, D., Cooper, J., Kronfli, R., Cananzi, M., Delalande, JM., McCann, C., Burns, A.J., and Thapar, N. (2015) Enteric neurospheres are not specific to neural crest cultures: implications for neural stem cell therapies. PLOS ONE 10(3) e0119467.

Natarajan, D., Cooper, J., Choudhury, S., Delalande, JM., McCann, C., Howe, S.J.,  Thapar, N.,  Burns A.J. (2014) Lentiviral labeling of mouse and human enteric nervous system stem cells for regenerative medicine studies. Neurogastroenterology and Motility 26(10); 1513-1518.

Delalande, JM., Vernay, B., Natarajan, D., Finlay, M., Ruhrberg, C., Thapar N., Burns, A.J.  (2014) Vascularisation is not necessary for gut colonisation by enteric neural crest cells. Developmental Biology 385(2); 200-229.

Burns, A.J., Thapar, N. (2014). Stem cell therapies for gut neuromuscular disorders. Nature Reviews Gastroenterology and Hepatology 11; 317-328.

Wang, X., Chan, A.K.K., Sham, M-H., Burns* A.J., Chan, W.Y. (2011) Analysis of the sacral neural crest cell contribution to the hindgut enteric nervous system in the mouse embryo. Gastroenterology 141(3): 992-1002.



Awards and Honours

UCL School of Life and Medical Sciences (SLMS) Academic Role Model.



Other Activities

  • Editorial Board Member: Developmental Biology (2016-current); Frontiers in Autonomic Neuroscience (2009-current); The Journal of Visualized Experiments (2011-current); Neurogastroenterology and Motility (2005-2010).
  • Member of AERES committee.
  • International conference organizer “Development of the enteric nervous system; cells, signals, genes and therapy”.
  • Co-founder of OptiShare, a web & mobile application designed to share otherwise discarded tissues or organs from laboratory mice.