The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Nick Wright : Histopathology
The Histopathology unit worked on gut cancer to explore how intestinal crypts are colonised by mutated stem cells, by using mitochondrial (mDNA) and genomic DNA mutations to map intracryptal spread of mutated stem cells. We champion the view that colonic adenomas grow by crypt fission, and are using mDNA mutations to examine clonal growth by fission, and the role of Wnt signalling. The lab also studyed the role of nutrients in gut growth control, and the effects of angiogenesis inhibitors on the development of gut tumours.
We have also shown that bone marrow stem cells contribute to hepatocytes in humans, into pericryptal myofibroblasts in the intestine, and also into tubular epithelium in both animals and man. We have demonstrated that bone marrow cells contribute significantly to keratinocytes in the epidermis and hair follicle, and also to fibroblasts and myofibroblasts in normal and healing tissues, including the stroma of animal and human tumours and liver scarring in cirrhosis. We have also found that entire new vessels - 'neovasculogenesis' - can form from bone marrow cells in inflammatory conditions in the adult intestine - previously only seen in the embryo. We have shown that such bone marrow cell lineages proliferate in situ. We have also successfully used lentovirally-transfected bone marrow stem cells to correct haemophilia in an experimental mouse model.
In the liver, our model is the hepatitis B surface antigen positive transgenic mouse, which develops chronic hepatitis and liver cancer. Targeting of bone marrow cells bearing interferon genes could colonise the liver with resistant hepatocytes. We also use several models of kidney and intestinal damage to study bone marrow stem cell engraftment, repair and regeneration. We will explore the mechanisms of bone marrow-derived vasculogenesis and how renal tubular cells are formed from bone marrow and clonally proliferate.
Selected Papers
Direkze NC, Forbes SJ, Brittan M, Hunt T, Jeffery R, Preston SL, Poulsom R, Hodivala-Dilke K, Alison MR, Wright NA. Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow transplanted mice. Stem Cells. 2003;21:514-20
(Abstract)
Novelli M, Cossu A, Oukrif D, Quaglia A, Lakhani S, Poulsom R, Sasieni P, Carta P, Contini M, Pasca A, Palmieri G, Bodmer W, Tanda F, Wright NA. -inactivation patch size in human female tissue confounds the assessment of tumor clonality. Proc Natl Acad Sci USA. 2003;100(6):3311-4
(Abstract)
Preston SL, Wong W-M, Chan AO-O, Poulsom R, Jeffery R, Goodlad RA, Mandir N, Elia G, Novelli M, Bodmer WF, Tomlinson IP and Wright NA. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res. 2003;63:3819-25
(Abstract)
Alison MR, Poulsom T, Jeffery R, Dhillon, AP Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. Plasticity of adult human haemopoietic stem cells: differentiation into hepatocytes after liver and bone marrow transplantation Nature. 2000;406:357
(Abstract)
Nick Wright