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Dr Toby Phesse
- Ar gael fel goruchwyliwr ôl-raddedig
Timau a rolau for Toby Phesse
Darllenydd
Ysgol y Biowyddorau
Cadeirydd y Pwyllgor Addasu Genetig ac Asiantau Biolegol Coleg y Gwyddorau Bywyd Biolegol
Staff Academaidd
Trosolwg
Mae gan fy ymchwil ddiddordeb mewn sut mae signalau celloedd yn rheoleiddio swyddogaeth celloedd mewn meinweoedd arferol, bôn-gelloedd a thiwmorau i gael mewnwelediad i sut mae canser yn cael ei gychwyn, yn tyfu ac yn metastasis. Yna rydym yn defnyddio'r wybodaeth hon i nodi targedau a strategaethau newydd i drin canserau amrywiol, gyda ffocws ar lwybr signalau Wnt yn y prostad a'r llwybr gastroberfeddol.
Ein nod yw defnyddio dull mainc wrth ochr y gwely lle mae ymchwil gymhwysol mewn modelau cyn-glinigol gan ddefnyddio technegau genetig a moleciwlaidd yn cael ei ategu â strategaethau ffarmacolegol gyda'n cydweithwyr diwydiannol a chlinigol gan alluogi cyfieithu i gymwysiadau clinigol posibl ac yn y pen draw gwella iechyd cleifion.
Aelodau'r labordy presennol:
Kieran Hodson (Ôl-ddoethurol)
Jess Hembrough (Myfyriwr PhD)
Sian Rizzo (Arbenigwr Technegol)
Cyhoeddiad
2026
- Swift, E. A. et al. 2026. Comparison of the in vivo biodistributions of αvβ6 binding agents for PET imaging applications. Molecular Therapy Oncology 34 (2) 201236. (10.1016/j.omton.2026.201236)
2025
- Mulholland, E. J. et al., 2025. Epithelial GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche through stromal remodelling. Nature Communications 16 (1) 5167. (10.1038/s41467-025-60364-6)
- Hodson, K. et al. 2025. Targeting cancer with Paris' arrow: An updated perspective on targeting Wnt Receptor Frizzled 7. Sci 7 (2) 61. (10.3390/sci7020061)
2024
- Badder, L. et al. 2024. The αvβ6 integrin specific virotherapy, Ad5NULL-A20.FCU1, selectively delivers 2 potent “in-tumour” chemotherapy to Pancreatic Ductal Adenocarcinoma. British Journal of Cancer 131 , pp.1694-1706. (10.1038/s41416-024-02869-3)
- Turnham, D. J. et al. 2024. Development and characterisation of a new patient-derived Xenograft model of AR-negative metastatic asctration-resistant prostate cancer. Cells 13 (8) 673. (10.3390/cells13080673)
2022
- Routledge, D. et al., 2022. The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife 11 e77376. (10.7554/elife.77376)
- Bates, E. A. et al. 2022. Development of a low seroprevalence, αvβ6 integrin selective virotherapy based on human adenovirus type 10. Molecular Therapy - Oncolytics 25 , pp.43-56. (10.1016/j.omto.2022.03.007)
- Koushyar, S. et al. 2022. Exploring the Wnt pathway as a therapeutic target for prostate cancer. Biomolecules 12 (2) 309. (10.3390/biom12020309)
2021
- Tran, B. M. et al., 2021. Frizzled7 activates β-catenin-dependent and β-catenin-independent Wnt signalling pathways during developmental morphogenesis: implications for therapeutic targeting in colorectal cancer. In: Schulte, G. and Kozielewicz, P. eds. Handbook of Experimental Pharmacology 269: Pharmacology of the WNT Signaling System. Vol. 269, Handbook of Experimental Pharmacology Vol. 269.Springer. , pp.251-278. (10.1007/164_2021_524)
2020
- Jardé, T. et al., 2020. Mesenchymal niche-derived neuregulin-1 drives intestinal stem cell proliferation and regeneration of damaged epithelium. Cell Stem Cell 27 (4), pp.646-662.E7. VOLUME 27, ISSUE 4, P646-662.E7, OCTOBER 01, 2020. (10.1016/j.stem.2020.06.021)
- Tran, B. M. et al., 2020. The hepatitis B virus pre-core protein p22 activates Wnt sgnaling. Cancers 12 (6) 1435. (10.3390/cancers12061435)
- Koushyar, S. et al. 2020. Targeting Wnt signaling for the treatment of gastric cancer. International Journal of Molecular Sciences 21 (11) 3927. (10.3390/ijms21113927)
2019
- Flanagan, D. J. , Vincan, E. and Phesse, T. J. 2019. Wnt signaling in cancer: not a binary ON:OFF switch. Cancer Research (10.1158/0008-5472.CAN-19-1362)
- Parry, L. and Phesse, T. J. 2019. FXR regulates intestinal stem cells response to bile acids in a high fat diet. Biotarget 3 (12)(10.21037/biotarget.2019.07.01)
- Flanagan, D. et al., 2019. The function of Lgr5+ cells in the gastric antrum does not require Fzd7 or Myc in vivo. Biomedicines 7 (3) 50. (10.3390/biomedicines7030050)
- Flanagan, D. J. et al., 2019. Frizzled-7 is required for Wnt signaling in gastric tumours with and without Apc mutations. Cancer Research 79 (5), pp.970-981. (10.1158/0008-5472.CAN-18-2095)
- Eissman, M. F. et al., 2019. IL-33 mediated mast cell activation promotes gastric cancer through macrophage mobilization. Nature Communications 10 2735. (10.1038/s41467-019-10676-1)
2018
- Greenow, K. R. et al., 2018. Lect2 deficiency is characterised by altered cytokine levels and promotion of intestinal tumourigenesis. Oncotarget 9 (92), pp.36430-36443. (10.18632/oncotarget.26335)
- May, S. et al. 2018. Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. Journal of Pathology 245 (3), pp.270-282. (10.1002/path.5074)
- Pearson, H. B. et al. 2018. Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth. Cancer Discovery 8 (6), pp.764-779. (10.1158/2159-8290.CD-17-0867)
- Flanagan, D. et al., 2018. Wnt Signalling in gastrointestinal epithelial stem cells. Genes 9 (4) 178. (10.3390/genes9040178)
- Vincan, E. et al., 2018. The central role of Wnt signaling and organoid technology in personalizing anticancer therapy. Progress in Molecular Biology and Translational Science 153 , pp.299-319. (10.1016/bs.pmbts.2017.11.009)
2017
- Phesse, T. , Marsh Durban, V. and Sansom, O. J. 2017. Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models. Carcinogenesis 38 (10), pp.953-965. (10.1093/carcin/bgx080)
- Flanagan, D. J. et al., 2017. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo. Disease Models and Mechanisms 10 (8), pp.971-980. (10.1242/dmm.029876)
- Phesse, T. J. and Sansom, O. J. 2017. Lgr5 joins the club of gastric stem cell markers in the corpus. Nature Cell Biology 19 (7), pp.752-754. (10.1038/ncb3567)
- Flanagan, D. J. , Vincan, E. and Phesse, T. J. 2017. Winding back Wnt signalling: potential therapeutic targets for treating gastric cancers. British Journal of Pharmacology 174 (24), pp.4666-4683. (10.1111/bph.13890)
- Schwab, R. H. et al., 2017. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Developmental Dynamics 247 (3), pp.521-530. (10.1002/dvdy.24527)
2016
- Flanagan, D. J. et al., 2016. Isolation and culture of adult intestinal, gastric, and lver organoids for cre-recombinase-mediated gene deletion. In: Methods in Molecular Biology. Humana Press. , pp.1-11. (10.1007/7651_2016_14)
- Togel, L. et al., 2016. Dual targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells. Molecular Cancer Therapeutics 15 (6), pp.1217-1226. (10.1158/1535-7163.MCT-15-0724)
- Phesse, T. , Flanagan, D. and Vincan, E. 2016. Frizzled7: a promising achilles' heel for targeting the Wnt receptor complex to treat cancer. Cancers 8 (5), pp.50. (10.3390/cancers8050050)
2015
- Pearson, H. B. et al. 2015. The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Molecular Cancer 14 169. (10.1186/s12943-015-0440-z)
- Flanagan, D. et al., 2015. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4 (5), pp.759-767. (10.1016/j.stemcr.2015.03.003)
2014
- Elsum, I. A. et al., 2014. Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene 33 (48), pp.5523-5533. (10.1038/onc.2013.498)
- Phesse, T. J. et al. 2014. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt–β-catenin–mediated intestinal tumor growth and regeneration. Science Signaling 7 (345) ra92. (10.1126/scisignal.2005411)
- Infantino, S. et al., 2014. The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice. Science Signaling 7 (338), pp.ra77. (10.1126/scisignal.2005105)
- Phesse, T. J. et al. 2014. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death and Differentiation 21 (6), pp.956-966. (10.1038/cdd.2014.15)
- Rickard, J. et al., 2014. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157 (5), pp.1175-1188. (10.1016/j.cell.2014.04.019)
- Hare, L. et al., 2014. Physiological expression of the PI3K-activating mutationPik3caH1047Rcombines withApcloss to promote development of invasive intestinal adenocarcinomas in mice. Biochemical Journal 458 (2), pp.251-258. (10.1042/BJ20131412)
- Stuart, E. et al., 2014. Therapeutic inhibition of jak activity inhibits progression of gastrointestinal tumors in mice. Molecular Cancer Therapeutics 13 (2), pp.468. (10.1158/1535-7163.MCT-13-0583-T)
2013
- Phesse, T. and Sansom, O. J. 2013. Responding to R-spondin: slit2 potentiates intestinal regeneration. Cell Stem Cell 13 , pp.512-514. (10.1016/j.stem.2013.10.006)
- Meniel, V. et al. 2013. Cited1 deficiency suppresses intestinal tumorigenesis. PLoS Genetics 9 (8) e1003638. (10.1371/journal.pgen.1003638)
2011
- Sakthianandeswaren, A. et al., 2011. PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. Cancer Research 71 (10), pp.3709-3719. (10.1158/0008-5472.CAN-10-2342)
2010
- Ashton, G. H. et al., 2010. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Developmental Cell 19 (2), pp.259-269. (10.1016/j.devcel.2010.07.015)
2009
- Pearson, H. B. , Phesse, T. and Clarke, A. R. 2009. K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse. Cancer Research 69 (1), pp.94-101. http://dx.doi.org/10.1158/0008-5472.CAN-08-2895. (10.1158/0008-5472.CAN-08-2895)
- Bollrath, J. et al., 2009. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15 (2), pp.91-102. (10.1016/j.ccr.2009.01.002)
- Burke, Z. D. et al., 2009. Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism. Gastroenterology 136 (7), pp.2316-2324. (10.1053/j.gastro.2009.02.063)
- Phesse, T. and Clarke, A. R. 2009. Normal stem cells in cancer prone epithelial tissues. British Journal of Cancer 100 (2), pp.221-227. (10.1038/sj.bjc.6604850)
2008
- Phesse, T. et al. 2008. Deficiency of Mbd2 attenuates Wnt induced tumourigenesis via deregulation of a novel Wnt inhibitor, Lect.2. Molecular and Cellular Biology 28 (19), pp.6094-6103. (10.1128/MCB.00539-08)
2007
- Sansom, O. J. et al. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446 (7136), pp.676-679. (10.1038/nature05674)
2006
- Muncan, V. et al., 2006. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Molecular and Cellular Biology 26 (22), pp.8418-8426. (10.1128/MCB.00821-06)
Adrannau llyfrau
- Tran, B. M. et al., 2021. Frizzled7 activates β-catenin-dependent and β-catenin-independent Wnt signalling pathways during developmental morphogenesis: implications for therapeutic targeting in colorectal cancer. In: Schulte, G. and Kozielewicz, P. eds. Handbook of Experimental Pharmacology 269: Pharmacology of the WNT Signaling System. Vol. 269, Handbook of Experimental Pharmacology Vol. 269.Springer. , pp.251-278. (10.1007/164_2021_524)
- Flanagan, D. J. et al., 2016. Isolation and culture of adult intestinal, gastric, and lver organoids for cre-recombinase-mediated gene deletion. In: Methods in Molecular Biology. Humana Press. , pp.1-11. (10.1007/7651_2016_14)
Erthyglau
- Swift, E. A. et al. 2026. Comparison of the in vivo biodistributions of αvβ6 binding agents for PET imaging applications. Molecular Therapy Oncology 34 (2) 201236. (10.1016/j.omton.2026.201236)
- Mulholland, E. J. et al., 2025. Epithelial GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche through stromal remodelling. Nature Communications 16 (1) 5167. (10.1038/s41467-025-60364-6)
- Hodson, K. et al. 2025. Targeting cancer with Paris' arrow: An updated perspective on targeting Wnt Receptor Frizzled 7. Sci 7 (2) 61. (10.3390/sci7020061)
- Badder, L. et al. 2024. The αvβ6 integrin specific virotherapy, Ad5NULL-A20.FCU1, selectively delivers 2 potent “in-tumour” chemotherapy to Pancreatic Ductal Adenocarcinoma. British Journal of Cancer 131 , pp.1694-1706. (10.1038/s41416-024-02869-3)
- Turnham, D. J. et al. 2024. Development and characterisation of a new patient-derived Xenograft model of AR-negative metastatic asctration-resistant prostate cancer. Cells 13 (8) 673. (10.3390/cells13080673)
- Routledge, D. et al., 2022. The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife 11 e77376. (10.7554/elife.77376)
- Bates, E. A. et al. 2022. Development of a low seroprevalence, αvβ6 integrin selective virotherapy based on human adenovirus type 10. Molecular Therapy - Oncolytics 25 , pp.43-56. (10.1016/j.omto.2022.03.007)
- Koushyar, S. et al. 2022. Exploring the Wnt pathway as a therapeutic target for prostate cancer. Biomolecules 12 (2) 309. (10.3390/biom12020309)
- Jardé, T. et al., 2020. Mesenchymal niche-derived neuregulin-1 drives intestinal stem cell proliferation and regeneration of damaged epithelium. Cell Stem Cell 27 (4), pp.646-662.E7. VOLUME 27, ISSUE 4, P646-662.E7, OCTOBER 01, 2020. (10.1016/j.stem.2020.06.021)
- Tran, B. M. et al., 2020. The hepatitis B virus pre-core protein p22 activates Wnt sgnaling. Cancers 12 (6) 1435. (10.3390/cancers12061435)
- Koushyar, S. et al. 2020. Targeting Wnt signaling for the treatment of gastric cancer. International Journal of Molecular Sciences 21 (11) 3927. (10.3390/ijms21113927)
- Flanagan, D. J. , Vincan, E. and Phesse, T. J. 2019. Wnt signaling in cancer: not a binary ON:OFF switch. Cancer Research (10.1158/0008-5472.CAN-19-1362)
- Parry, L. and Phesse, T. J. 2019. FXR regulates intestinal stem cells response to bile acids in a high fat diet. Biotarget 3 (12)(10.21037/biotarget.2019.07.01)
- Flanagan, D. et al., 2019. The function of Lgr5+ cells in the gastric antrum does not require Fzd7 or Myc in vivo. Biomedicines 7 (3) 50. (10.3390/biomedicines7030050)
- Flanagan, D. J. et al., 2019. Frizzled-7 is required for Wnt signaling in gastric tumours with and without Apc mutations. Cancer Research 79 (5), pp.970-981. (10.1158/0008-5472.CAN-18-2095)
- Eissman, M. F. et al., 2019. IL-33 mediated mast cell activation promotes gastric cancer through macrophage mobilization. Nature Communications 10 2735. (10.1038/s41467-019-10676-1)
- Greenow, K. R. et al., 2018. Lect2 deficiency is characterised by altered cytokine levels and promotion of intestinal tumourigenesis. Oncotarget 9 (92), pp.36430-36443. (10.18632/oncotarget.26335)
- May, S. et al. 2018. Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. Journal of Pathology 245 (3), pp.270-282. (10.1002/path.5074)
- Pearson, H. B. et al. 2018. Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth. Cancer Discovery 8 (6), pp.764-779. (10.1158/2159-8290.CD-17-0867)
- Flanagan, D. et al., 2018. Wnt Signalling in gastrointestinal epithelial stem cells. Genes 9 (4) 178. (10.3390/genes9040178)
- Vincan, E. et al., 2018. The central role of Wnt signaling and organoid technology in personalizing anticancer therapy. Progress in Molecular Biology and Translational Science 153 , pp.299-319. (10.1016/bs.pmbts.2017.11.009)
- Phesse, T. , Marsh Durban, V. and Sansom, O. J. 2017. Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models. Carcinogenesis 38 (10), pp.953-965. (10.1093/carcin/bgx080)
- Flanagan, D. J. et al., 2017. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo. Disease Models and Mechanisms 10 (8), pp.971-980. (10.1242/dmm.029876)
- Phesse, T. J. and Sansom, O. J. 2017. Lgr5 joins the club of gastric stem cell markers in the corpus. Nature Cell Biology 19 (7), pp.752-754. (10.1038/ncb3567)
- Flanagan, D. J. , Vincan, E. and Phesse, T. J. 2017. Winding back Wnt signalling: potential therapeutic targets for treating gastric cancers. British Journal of Pharmacology 174 (24), pp.4666-4683. (10.1111/bph.13890)
- Schwab, R. H. et al., 2017. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Developmental Dynamics 247 (3), pp.521-530. (10.1002/dvdy.24527)
- Togel, L. et al., 2016. Dual targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells. Molecular Cancer Therapeutics 15 (6), pp.1217-1226. (10.1158/1535-7163.MCT-15-0724)
- Phesse, T. , Flanagan, D. and Vincan, E. 2016. Frizzled7: a promising achilles' heel for targeting the Wnt receptor complex to treat cancer. Cancers 8 (5), pp.50. (10.3390/cancers8050050)
- Pearson, H. B. et al. 2015. The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Molecular Cancer 14 169. (10.1186/s12943-015-0440-z)
- Flanagan, D. et al., 2015. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4 (5), pp.759-767. (10.1016/j.stemcr.2015.03.003)
- Elsum, I. A. et al., 2014. Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene 33 (48), pp.5523-5533. (10.1038/onc.2013.498)
- Phesse, T. J. et al. 2014. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt–β-catenin–mediated intestinal tumor growth and regeneration. Science Signaling 7 (345) ra92. (10.1126/scisignal.2005411)
- Infantino, S. et al., 2014. The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice. Science Signaling 7 (338), pp.ra77. (10.1126/scisignal.2005105)
- Phesse, T. J. et al. 2014. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death and Differentiation 21 (6), pp.956-966. (10.1038/cdd.2014.15)
- Rickard, J. et al., 2014. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157 (5), pp.1175-1188. (10.1016/j.cell.2014.04.019)
- Hare, L. et al., 2014. Physiological expression of the PI3K-activating mutationPik3caH1047Rcombines withApcloss to promote development of invasive intestinal adenocarcinomas in mice. Biochemical Journal 458 (2), pp.251-258. (10.1042/BJ20131412)
- Stuart, E. et al., 2014. Therapeutic inhibition of jak activity inhibits progression of gastrointestinal tumors in mice. Molecular Cancer Therapeutics 13 (2), pp.468. (10.1158/1535-7163.MCT-13-0583-T)
- Phesse, T. and Sansom, O. J. 2013. Responding to R-spondin: slit2 potentiates intestinal regeneration. Cell Stem Cell 13 , pp.512-514. (10.1016/j.stem.2013.10.006)
- Meniel, V. et al. 2013. Cited1 deficiency suppresses intestinal tumorigenesis. PLoS Genetics 9 (8) e1003638. (10.1371/journal.pgen.1003638)
- Sakthianandeswaren, A. et al., 2011. PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. Cancer Research 71 (10), pp.3709-3719. (10.1158/0008-5472.CAN-10-2342)
- Ashton, G. H. et al., 2010. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Developmental Cell 19 (2), pp.259-269. (10.1016/j.devcel.2010.07.015)
- Pearson, H. B. , Phesse, T. and Clarke, A. R. 2009. K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse. Cancer Research 69 (1), pp.94-101. http://dx.doi.org/10.1158/0008-5472.CAN-08-2895. (10.1158/0008-5472.CAN-08-2895)
- Bollrath, J. et al., 2009. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15 (2), pp.91-102. (10.1016/j.ccr.2009.01.002)
- Burke, Z. D. et al., 2009. Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism. Gastroenterology 136 (7), pp.2316-2324. (10.1053/j.gastro.2009.02.063)
- Phesse, T. and Clarke, A. R. 2009. Normal stem cells in cancer prone epithelial tissues. British Journal of Cancer 100 (2), pp.221-227. (10.1038/sj.bjc.6604850)
- Phesse, T. et al. 2008. Deficiency of Mbd2 attenuates Wnt induced tumourigenesis via deregulation of a novel Wnt inhibitor, Lect.2. Molecular and Cellular Biology 28 (19), pp.6094-6103. (10.1128/MCB.00539-08)
- Sansom, O. J. et al. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446 (7136), pp.676-679. (10.1038/nature05674)
- Muncan, V. et al., 2006. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Molecular and Cellular Biology 26 (22), pp.8418-8426. (10.1128/MCB.00821-06)
Ymchwil
Fy mhrif ddiddordeb ymchwil yw deall sut mae signalau celloedd yn rheoli homeostasis, adfywio, swyddogaeth bôn-gelloedd a chlefyd, gyda ffocws ar signalau Wnt yn y llwybr gastroberfeddol. Mae llawer o'r llwybrau signalau celloedd sy'n hanfodol ar gyfer datblygiad embryonig, homeostasis ac adfywio meinweoedd epithelial yn cael eu dadreoleiddio yn ystod clefyd, ac yn enwedig canser. Felly, trwy ddeall y digwyddiadau moleciwlaidd sy'n rheoleiddio signalau celloedd yn ystod y prosesau biolegol hyn, a'r aberrations sy'n arwain at ddadreoleiddio a chlefydau, rydym yn anelu at nodi strategaethau therapiwtig newydd.
Mae fy labordy yn defnyddio cyfuniad o dechnegau in vitro datblygedig, fel diwylliannau organoid (Ffig. 1), ynghyd â modelau llygoden soffistigedig (Ffig. 2), i gael mewnwelediadau newydd i'r gofyniad am signalau celloedd yn ystod bioleg yr epitheliwm gastroberfeddol oedolion, a thrwy hynny ddeall sut mae signalau wedi'u dadreoleiddio yn arwain at glefyd.
Mae bôn-gelloedd yn gysylltiedig â chanser, gan eu bod wedi cael eu dangos yn aml fel cell tarddiad ar gyfer sawl canser gwahanol gan gynnwys y coluddyn. Mae darganfod Lgr5 fel marciwr bôn-gelloedd coluddyn wedi darparu offeryn ymchwil pwerus i alluogi mewnwelediad pellach i fioleg y coluddyn a rôl bôn-gelloedd mewn canser. Yn wir, mae Lgr5 hefyd yn nodi poblogaeth o fôn-gelloedd canser sy'n gallu darparu priodweddau amlhau a hunan-adnewyddu tiwmorau coluddyn. Felly, mae deall beth sy'n rheoleiddio bôn-gelloedd yn ddiddordeb mawr yn y maes ac mae gan ein labordy ddiddordeb arbennig yn rôl signalau Wnt.
Er bod y llwybr Wnt wedi'i ddadreoleiddio mewn tua 85% o diwmorau'r colon, mae hefyd ei angen, ar lefelau is, ar gyfer swyddogaeth homeostatig arferol y coluddyn, ac yn ystod adfywio. Mae'r trawsnewidyddion signal cytoplasmig sy'n gysylltiedig â signalau Wnt wedi'u nodweddu'n dda, ac mae'r ymchwil gyfredol yn parhau i gael mewnwelediadau newydd i'w gymhlethdod a'i ryngweithio â llwybrau eraill (Bollrath a Phesse et al, Cancer Cell, 2009 a Phesse et al, Science Signalling, 2014). O'i gymharu â'r rheoleiddwyr Wnt cytoplasmig, mae'r cymhleth derbynnydd Wnt yn cael ei ddeall yn gymharol wael. Yn wir, nid yw'n cael ei ddogfennu'n llawn o hyd pa un o'r 10 derbynnydd Wnt Frizzled mamalaidd sy'n rhwymo i ba un o'r 19 ligand Wnt mamalaidd. Dim ond yn 2015 y gwnaethom ddangos mai Frizzled7 yw'r derbynnydd Wnt mwyaf sy'n ofynnol ar gyfer swyddogaeth bôn-gelloedd coluddyn a gastrig (Flanagan a Phesse et al, Stem Cell Reports, 2015, adolygwyd yn Phesse et al, Cancers, 2016 a Flanagan et al., DMM, 2017), ac mae prosiectau cyfredol yn ymchwilio i rôl y derbynnydd hwn mewn organau a lleoliadau clefydau eraill gan gynnwys targedu signalau Wnt mewn canser y prostad metastatig.
Yn ddiweddar, rydym wedi sicrhau cyllid mawr gan Prostate Cancer UK (https://prostatecanceruk.org/research/research-we-fund/ria24-st2-003) ac Ymchwil Canser Cymru (https://www.cancerresearch.wales/research/our-research/our-projects/investigating-the-function-of-fzd7-in-cholangiocarcinoma-and-determining-the-therapeutic-benefit-of-targeting-fzd7-with-a-novel-fzd7-adc)
Cydweithwyr Allweddol
Yr Athro Owen Sansom – Beatson CRUK, Yr Alban
Yr Athro Elizabeth Vincan – Prifysgol Melbourne, Awstralia
Yr Athro Karl Willert – Prifysgol California, San Diego
Addysgu
Rwy'n rhoi darlithoedd, gweithdai a thiwtorialau mewn sawl pwnc gan gynnwys, bioleg foleciwlaidd, bioleg celloedd, therapi canser a bôn-gelloedd.
Ar hyn o bryd rwy'n dysgu yn y modiwlau canlynol yng Nghaerdydd:
- Bioleg Moleciwlaidd y Genyn
- Mecanweithiau Moleciwlaidd a Chellog Iechyd Dynol
- Pynciau Cyfoes mewn Clefydau
- Canser: Celloedd a Moleciwlaidd Mechanisndms a Therapiwteg
Rwy'n cyd-arweinydd ar gyfer Mecanweithiau Moleciwlaidd a Chellog Iechyd Pobl.
Rwy'n arwain Ymchwil Ôl-raddedig yn yr Is-adran Biofeddygaeth
Rwy'n Gymrawd o'r Academi Addysg Uwch (FHEA), ac yn mynd ati i ddefnyddio'r holl addysgu.
Bywgraffiad
Dyfarnwyd PhD i Dr Phesse o Brifysgol Warwick lle astudiodd y cydweithrediad rhwng signalau Wnt a signalau TGF-β yn ystod datblygiad embryonig. Yn ystod y prosiect hwn dysgodd am y rôl bwysig a chwaraeodd signalau Wnt yn ystod canser, ac wedi hynny sicrhaodd swydd ôl-ddoethurol yn labordy yr Athro Alan Clarke ym Mhrifysgol Caerdydd. Yn labordy Alan y meithrin ei brif ddiddordeb ymchwil, gan astudio sut mae signalau celloedd yn rheoleiddio homeostasis, swyddogaeth bôn-gelloedd, adfywio a chanser. Mae ei waith wedi canolbwyntio'n bennaf ar lwybr signalau Wnt a'r llwybr gastroberfeddol, er ei fod hefyd wedi ymchwilio i organau eraill gan gynnwys yr afu, y prostad a'r croen, gyda'r nod sylfaenol o nodi strategaethau therapiwtig newydd ar gyfer trin canser.
Ar ôl tair blynedd lwyddiannus gydag Alan, enillodd Toby Gymrodoriaeth gan y Cyngor Prydeinig i weithio yn Sefydliad Ludwig ym Melbourne i astudio'r rhyngweithio rhwng signalau Wnt a signalau gp130/Stat3 mewn canser GI. Cyhoeddodd y gwaith hwn yn Cancer Cell yn 2009 sydd wedi cael ei ddyfynnu ers hynny dros 700 o weithiau. Wedi hynny, cynhaliodd gyllid parhaus y Cyngor Ymchwil Feddygol Iechyd Cenedlaethol am y 6 blynedd canlynol a alluogodd ef i reoli grŵp ymchwil bach mewn amrywiaeth o sefydliadau, gan gynnwys Sefydliad mawreddog Walter ac Eliza Hall a Phrifysgol Melbourne, gan astudio rôl signalau celloedd mewn adfywio a chanser.
Yn 2016 fe'i penodwyd yn Uwch Gymrawd Ymchwil a phennaeth cyd-labordy ym Mhrifysgol Melbourne, cyn derbyn cymrodoriaethau ychwanegol yn y DU (Ymddiriedolaeth Wellcome a Phrifysgol Caerdydd) i hwyluso ei symud yn ôl i Gaerdydd fel Cymrawd yn Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop ym Mhrifysgol Caerdydd. Yn 2019 fe'i penodwyd yn Uwch Gymrawd Ymchwil, ac yn 2021 yn Ddarlithydd, yn Uwch Ddarlithydd yn 2023 a Darllenydd yn 2026.
Mae ganddo swydd barhaus ym Mhrifysgol Melbourne fel Uwch Gymrawd er Anrhydedd, gan gynnal cysylltiadau agos yno gyda chyd-ariannu a diddordebau ymchwil agos gyda chydweithwyr yno.
Anrhydeddau a dyfarniadau
Uwch Gymrawd Anrhydeddus ym Mhrifysgol Melbourne, Awstralia.
Aelodaethau proffesiynol
Cymrawd yr Academi Addysg Uwch
Safleoedd academaidd blaenorol
|
2023-presennol |
Uwch Ddarlithydd, Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop, Prifysgol Caerdydd. |
|
2021- 2023 |
Darlithydd, Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop, Prifysgol Caerdydd. |
|
2018 – presennol |
Uwch Gymrawd Tenured yn Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop, Prifysgol Caerdydd. |
|
2016 - presennol |
Cymrawd Ymchwil Arweinydd Grŵp yn Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop, Prifysgol Caerdydd. |
|
2016 - presennol |
Uwch Gymrawd Anrhydeddus, Sefydliad Doherty, Prifysgol Melbourne, Awstralia. |
|
2016 |
Pennaeth Cyd-labordy gyda'r Athro Vincan, Sefydliad Doherty, Prifysgol Melbourne, Awstralia. |
|
2012 – 2015 |
Uwch Gymrawd Ôl-ddoethurol yn Sefydliad Ymchwil Meddygol Walter ac Eliza Hall, Melbourne, Awstralia. |
|
2008 - 2012 |
Uwch Gymrawd Ôl-ddoethurol yn Sefydliad Ymchwil Canser Ludwig Cyf. yn labordy yr Athro Matthias Ernst, Melbourne, Awstralia. |
|
2008 - 2012 |
Cymrawd Anrhydeddus Prifysgol Melbourne, Adran Llawfeddygaeth ac Adran Bioleg Feddygol, Awstralia, Melbourne. |
|
2004 - 2008 |
Postfeddyg ym Mhrifysgol Caerdydd, y DU yn labordy'r Athro Alan Clarke. |
Ymrwymiadau siarad cyhoeddus
Prif Siaradwr yn Inaugural WntUK COnference, Llundain, 2024.
Pwyllgorau ac adolygu
Adolygydd Grant ar gyfer MRC, BBSRC, NHMRC (Aus), Ymchwil Canser Fyd-eang, Sefydliad Croen Prydain, Ymchwil Coluddyn y DU, Ymddiriedolaeth Leverhulme, a Phrifysgol Tel-Aviv.
Adolygydd Journal ar gyfer llawer o gyfnodolion gan gynnwys Nature, Nat Cell Biol, EMBO Reports, Oncogene, Carcinogenesis a DMM.
Aelod Panel REF2021 ac Adolygiad REF2028 mewnol.
Cadeirydd Pwyllgor Grantiau Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop.
Aelod o'r Panel ar gyfer Bwrdd Cynghori Athena Swann ar Rieni a Gofalwyr.
Meysydd goruchwyliaeth
Mae gen i ddiddordeb mewn goruchwylio myfyrwyr PhD ym meysydd:
- Signalau Wnt
- Canser gastroberfeddol
- Canser y prostad
- Cholangiocarcinoma
- Virotherapy ar gyfer canser
Goruchwyliaeth gyfredol
Ymgysylltu
ArrayNews articles
Contact Details
Themâu ymchwil
Arbenigeddau
- Bioleg celloedd canser
- Therapi canser
- Celloedd bonyn
- Signalau Wnt
