Research and publications

The clinical academic unit of paediatric gastroenterology is a partnership across Great Ormond Street Hospital and UCL Great Ormond Street Institute of Child Health and is involved in a large spectrum of research.

Research

The research involves both laboratory and patient based research work with the emphasis on translation and innovation to benefit children suffering from both common and rarer complex gastrointestinal disease.

Neurogastroenterology and gut motility disorders

There is a large research programme studying the normal and aberrant development of gut nerves, muscles and interstitial cells of Cajal and the congenital gut motility disorders such as Hirschsprung’s disease, intestinal pseudo-obstruction etc that result from the latter.

In addition the team is studying the mechanisms underlying acquired disorders such as gut inflammatory and allergy related dysmotility including gastro-oesophageal reflux and constipation and use of contemporary technologies for diagnosis and treatment.

Much of the work centres on the interaction between the immune system and the gut neuromusculature. A particular focus also includes the development of stem cell therapies to replenish absent or abnormal nerves and muscles in gut motility disorders.

Genetics

A large number of gastrointestinal disorders are inherited or the result of abnormalities in the various genes that determine normal structure and function of the gut or of its supporting systems e.g. blood vessels, immune cells.

The research group has been investigating a range of gut disorders that result for genetic mutations with the hope that this will allow better counselling of patients and families, guide prognosis and treatment, and provide targets for future curative treatments e.g. genetherapy.

To date the group have worked on the genetics of congenital diarrhoea syndromes, inflammatory and neuromuscular disorders of the gut and 

Intestinal failure

Great Ormond Street Hospital is a large tertiary referral centre for paediatric surgery and children with insufficient functional gut, either due to anatomical loss due to disease and surgery, or a failure of the gut to carry out its absorptive, digestive or motility functions. Such children often require artificial (parenteral) nutrition and repeated surgery.

Current research is looking to understand the outcomes of intestinal failure, reduce complications related to providing artificial nutrition (e.g. sepsis, liver disease, vascular thrombosis, central venous line failure), and ultimately develop new treatments e.g. gut tissue engineering. Collaborative research is also exploring aspects of intestinal transplantation.

Autoimmune and inflammatory gut diseases

A number of gastrointestinal conditions arise from disorders in the immune system, which appears to lose its normal protective function to one that harms the body’s own tissues and organs (autoimmune).

Research areas include gut and systemic immune function, the interaction between gut bacteria and epithelia, and use of newer theories for treatment e.g. emerging pharmacotherapeutic agents and bone marrow transplant.

Publications

Publications in the past three years in these and other areas include:

Reference 1

Bhutta ZA, Nelson EA, Lee WS, Tarr PI, Zablah R, Phua KB, Lindley K, Bass D, Phillips A, Persistent Diarrhea Working Group (2008) Recent advances and evidence gaps in persistent diarrhea. J Pediatr Gastroenterol Nutr 47 (2): 260-5

Reference 2

Jarvi K, Roebuck DJ, Sebire NJ, Lindley K, Shah N, Salomon J, Curry JI (2008) Successful treatment of extensive infantile hemangiomatosis of the small bowel in a 3-month-old with thalidomide and somatostatin analog. J Pediatr Gastroenterol Nutr 46 (5): 593-7

Reference 3

Hotta R, Natarajan D, Thapar N (2009) Potential of cell therapy to treat pediatric motility disorders. Semin Pediatr Surg 18 (4): 263-73

Reference 4

Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N (2009) Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology 136 (7): 2214-25.e1-3

Reference 5

Wallace AS, Barlow AJ, Navaratne L, Delalande JM, Tauszig-Delamasure S, Corset V, Thapar N, Burns AJ (2009) Inhibition of cell death results in hyperganglionosis: implications for enteric nervous system development. Neurogastroenterol Motil 21 (7): 768-e49

Reference 6

Thapar N (2009) New frontiers in the treatment of Hirschsprung disease. J Pediatr Gastroenterol Nutr 48 Suppl 2 (): S92-4

Reference 7

Barlow AJ, Wallace AS, Thapar N, Burns AJ (2008) Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development 135 (9): 1681-91

Reference 8

Thapar N, Lindley KJ, Kiparissi F, Elawad MA, Ashworth M, Veys P, Gaspar HB, Hill SM, Milla PJ, Shah N (2008) Treatment of intractable ulcerating enterocolitis of infancy by allogeneic bone marrow transplantation. Clin Gastroenterol Hepatol 6 (2): 248-50

Reference 9

Delalande JM, Barlow AJ, Thomas AJ, Wallace AS, Thapar N, Erickson CA, Burns AJ (2008) The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells. Dev Biol 313 (1): 279-92

Reference 10

Burns AJ, Thapar N, Barlow AJ (2008) Development of the neural crest-derived intrinsic innervation of the human lung. Am J Respir Cell Mol Biol 38 (3): 269-75

Reference 11

Smith VV, Schäppi MG, Bisset WM, Kiparissi F, Jaffe A, Milla PJ, Lindley KJ (2009) Lymphocytic leiomyositis and myenteric ganglionitis are intrinsic features of cystic fibrosis: studies in distal intestinal obstruction syndrome and meconium ileus. J Pediatr Gastroenterol Nutr 49 (1): 42-51