Luke Boulter Research Group

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Research in a Nutshell 

During tissue homeostasis and regeneration epithelial cells must balance proliferation, cell death and differentiation to maintain a functional organ. In the liver, this regulation requires the constant integration of signals by epithelial cells from non-epithelial, niche cells, which includes inflammatory cells and fibroblasts. In cancer, these interactions become deregulated and epithelial cells can either be regulated independent of their microenvironment or the niche becomes permissive to tumour formation. 

Our lab is interested in how the signals, which come from the regenerative microenvironment drive tissue repair following injury and how these signals are co-opted by the tumour to support cancer growth. We are particularly interested in the role of the Wnt pathway in these processes and are currently working on both canonical and non-canonical Wnt signalling to define how these pathways regulate tissue architecture, using the adult liver and cancers of the adult liver as a models for these studies.

Research Programme

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Contact

 Luke.Boulter@ed.ac.uk

Publications

1. Waddell SH, Yao Y, Olaizola P, Walker A, Jarman EJ, Gournopanos K, Gradinaru A, Christodoulou E, Gautier P, Boerrigter MM, Cadamuro M, Fabris L, Drenth JP, Kendall TJ, Banales JM, Khamseh A, Mill P, Boulter L. A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease. Sci Transl Med. 2023 Sep 13;15(713):eabq5930. doi: 10.1126/scitranslmed.abq5930. Epub 2023 Sep 13. PMID: 37703354; PMCID: PMC7615241.
2. Younger NT, Wilson ML, Martinez Lyons A, Jarman EJ, Meynert AM, Grimes GR, Gournopanos K, Waddell SH, Tennant PA, Wilson DH, Guest RV, Wigmore SJ, Acosta JC, Kendall TJ, Taylor MS, Sproul D, Mill P, Boulter L. In Vivo Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma. Cancer Res. 2022 Apr 15;82(8):1548-1559. doi: 10.1158/0008-5472.CAN-21-2556. PMID: 35074757; PMCID: PMC9359731.
3. Wilson DH, Jarman EJ, Mellin RP, Wilson ML, Waddell SH, Tsokkou P, Younger NT, Raven A, Bhalla SR, Noll ATR, Olde Damink SW, Schaap FG, Chen P, Bates DO, Banales JM, Dean CH, Henderson DJ, Sansom OJ, Kendall TJ, Boulter L. Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors. Nat Commun. 2020 Jan 23;11(1):445. doi: 10.1038/s41467-020-14283-3. PMID: 31974352; PMCID: PMC6978415.
4. Raven A, Lu WY, Man TY, Ferreira-Gonzalez S, O'Duibhir E, Dwyer BJ, Thomson JP, Meehan RR, Bogorad R, Koteliansky V, Kotelevtsev Y, Ffrench-Constant C, Boulter L, Forbes SJ. Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature. 2017 Jul 20;547(7663):350-354. doi: 10.1038/nature23015. Epub 2017 Jul 12. Erratum in: Nature. 2018 Mar 14;555(7696):402. PMID: 28700576; PMCID: PMC5522613.
5. Boulter L, Guest RV, Kendall TJ, Wilson DH, Wojtacha D, Robson AJ, Ridgway RA, Samuel K, Van Rooijen N, Barry ST, Wigmore SJ, Sansom OJ, Forbes SJ. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest. 2015 Mar 2;125(3):1269-85. doi: 10.1172/JCI76452. Epub 2015 Feb 17. PMID: 25689248; PMCID: PMC4362247.

Full publication list can be found on Research Explorer: Luke Boulter — University of Edinburgh Research Explorer