![Matthew Smalley BA (Hons) (Oxon) PhD](https://profiles-cardiff.imgix.net/attachments/1222?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Yr Athro Matthew Smalley
BA (Hons) (Oxon) PhD
Timau a rolau for Matthew Smalley
Athro
Ysgol y Biowyddorau
Trosolwyg
Mae fy ngrŵp yn ceisio deall yr amrywiadau genetig sy'n gwneud gwahanol unigolion yn dueddol o wahanol fathau o ganser, gan weithio'n agos gyda patholegwyr milfeddygol ac oncolegwyr i astudio canser mewn cŵn. Mae gwahanol fridiau cŵn mewn perygl o wahanol fathau o ganser (er enghraifft, mae springer spaniels Saesneg mewn mwy o berygl o ganser mamari, o'i gymharu â chroesfridiau, tra bod rottweiler mewn mwy o berygl o osteosarcoma) ac felly maent yn system ddelfrydol i nodi ffactorau genetig sy'n effeithio ar risg canser.
Fel sgil-gynnyrch cyfeiriad newydd ein gwaith, rydym hefyd wedi dechrau datblygu marcwyr prognostig a rhagfynegol moleciwlaidd newydd i helpu i reoli tiwmorau mewn anifeiliaid cydymaith yn glinigol.
Cyhoeddiad
2024
- Williams, J. S. et al. 2024. Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc. Cell & Bioscience 14(38) (10.1186/s13578-024-01206-8)
- Tornillo, G., Warrington, L., Kendrick, H., Higgins, A. T., Hay, T., Beck, S. and Smalley, M. J. 2024. Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model. Disease Models and Mechanisms 17(1), article number: dmm050211. (10.1242/dmm.050211)
2023
- Varney, D. et al. 2023. Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016. Veterinary Record 193(5), article number: e3054. (10.1002/vetr.3054)
- Ordonez, L., Tornillo, G., Kendrick, H., Hay, T. and Smalley, M. J. 2023. NOTCH and AKT signalling interact to drive mammary tumour heterogeneity. Cancers 15(17), article number: 4324. (10.3390/cancers15174324)
- O'Neill, D., Edmunds, G., Urquhart-Gilmore, J., Church, D., Rutherford, L., Smalley, M. and Brodbelt, D. 2023. Dog breeds and conformations predisposed to osteosarcoma in the UK: a VetCompass study. Canine Medicine and Genetics 10, article number: 8. (10.1186/s40575-023-00131-2)
- Edmunds, G., Beck, S., Umakant Kale, K., Spasic, I., O'Neill, D., Brodbelt, D. and Smalley, M. J. 2023. Associations between dog breed and clinical features of mammary epithelial neoplasia in bitches: an epidemiological study of submissions to a single diagnostic pathology centre between 2008-2021. Journal of Mammary Gland Biology and Neoplasia 28(6) (10.1007/s10911-023-09531-3)
- Shorning, B., Trent, N., Griffiths, D. F., Worzfeld, T., Offermanns, S., Smalley, M. J. and Williamson, M. 2023. Plexin-B1 mutation drives metastasis in prostate cancer mouse models. Cancer Research Communications 3(3), pp. 444-458. (10.1158/2767-9764.CRC-22-0480)
2022
- Dimitriou, P., Li, J., Tornillo, G., Smalley, M. and Barrow, D. 2022. Droplet incubator: a new droplet-based model to investigate living cell-synthetic cell interactions. Presented at: MicroTAS 2022, Hangzhou, China, 23-27 October 2022.
2021
- Castro, J. et al. 2021. A nuclear-directed ribonuclease variant targets cancer stem cells and inhibits migration and invasion of breast cancer cells. Cancers 13(17), article number: 4350. (10.3390/cancers13174350)
- Ordonez, L. D. et al. 2021. Reproductive history determines ErbB2 locus amplification, WNT signalling and tumour phenotype in a murine breast cancer model. Disease Models and Mechanisms 14(5), article number: dmm048736. (10.1242/dmm.048736)
- Edmunds, G. L. et al. 2021. Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study. Canine Medicine and Genetics 8, article number: 2. (10.1186/s40575-021-00100-7)
2020
- Pires, A. et al. 2020. Immune remodelling of the extracellular matrix drives loss of cancer stem cells and tumor rejection. Cancer Immunology Research 8(12), pp. 1520 - 1531. (10.1158/2326-6066.CIR-20-0070)
- Regan, J. L. and Smalley, M. J. 2020. Integrating single-cell RNA-sequencing and functional assays to decipher mammary cell states and lineage hierarchies. NPJ Breast Cancer 6, article number: 32. (10.1038/s41523-020-00175-8)
- Shorning, B. Y., Dass, M. S., Smalley, M. J. and Pearson, H. B. 2020. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. International Journal of Molecular Sciences 21(12), article number: 4507. (10.3390/ijms21124507)
2019
- Ordonez, L. D. et al. 2019. Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in Brca2-mutant mammary tumours. Oncotarget 10(27), pp. 2586-2606. (10.18632/oncotarget.26830)
- Mohamed, N., Hay, T., Reed, K. R., Smalley, M. J. and Clarke, A. R. 2019. APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. BMC Cancer 19, article number: 677. (10.1186/s12885-019-5867-y)
2018
- Tornillo, G. et al. 2018. Dual mechanisms of LYN kinase dysregulation drive aggressive behaviour in breast cancer cells. Cell Reports 25(13), pp. 3674-3692. (10.1016/j.celrep.2018.11.103)
- 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)
2017
- Jefferies, M. T. et al. 2017. PTEN loss and activation of K-RAS and β-catenin cooperate to accelerate prostate tumourigenesis. Journal of Pathology 243(4), pp. 442-456. (10.1002/path.4977)
- Chiang, K. et al. 2017. PRMT5 is a critical regulator of breast cancer stem cell function via Histone Methylation and FOXP1 expression. Cell Reports 21(12), pp. 3498-3513. (10.1016/j.celrep.2017.11.096)
- Soady, K. J. et al. 2017. Receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis. Development 144(20), pp. 3777-3788. (10.1242/dev.149120)
2016
- Jardé, T. et al. 2016. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nature Communications 7, article number: 13207. (10.1038/ncomms13207)
- Abraham, T. et al. 2016. Ellipsoid segmentation model for analyzing light-attenuated 3D confocal image stacks of fluorescent multi-cellular spheroids. PLoS ONE 11(6), article number: e0156942. (10.1371/journal.pone.0156942)
- Estrada, M. F. et al. 2016. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. Biomaterials 78, pp. 50-61. (10.1016/j.biomaterials.2015.11.030)
2015
- Ferrari, N. et al. 2015. Runx2 contributes to the regenerative potential of the mammary epithelium. Scientific Reports 5, article number: 15658. (10.1038/srep15658)
- Greenow, K. R. and Smalley, M. J. 2015. Overview of genetically engineered mouse models of breast cancer used in translational biology and drug development. Current Protocols in Pharmacology 70(1), article number: 70:14.36.1-14.36.14. (10.1002/0471141755.ph1436s70)
- Tornillo, G. and Smalley, M. J. 2015. ERrrr..Where are the progenitors? Hormone receptors and mammary cell heterogeneity. Journal of Mammary Gland Biology and Neoplasia 20(1), pp. 63-73. (10.1007/s10911-015-9336-1)
- Francis, J. C. et al. 2015. Whole exome DNA sequence analysis of Brca2 and Trp53 deficient mouse mammary gland tumours. Journal of Pathology 236(2), pp. 186-200. (10.1002/path.4517)
- Iglesias, J. M. et al. 2015. Annexin A8 identifies a subpopulation of transiently quiescent c-Kit positive luminal progenitor cells of the ductal mammary epithelium. Plos One 10(3), article number: e0119718. (10.1371/journal.pone.0119718)
- Soady, K. J. et al. 2015. Mouse mammary stem cells express prognostic markers for triple-negative breast cancer. Breast Cancer Research 17, article number: 31. (10.1186/s13058-015-0539-6)
2014
- Hickman, J. A. et al. 2014. Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo. Biotechnology Journal 9(9), pp. 1115-1128. (10.1002/biot.201300492)
- Melchor, L. et al. 2014. Identification of cellular and genetic drivers of breast cancer heterogeneity in genetically engineered mouse tumour models. Journal of Pathology 233(2), pp. 124-137. (10.1002/path.4345)
- Cowley, M. et al. 2014. Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. PLoS Biology 12(2), pp. e1001799. (10.1371/journal.pbio.1001799)
2013
- Regan, J. et al. 2013. Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner. Cell Reports 4(1), pp. 110-123. (10.1016/j.celrep.2013.05.044)
- Gastaldi, S. et al. 2013. Met signaling regulates growth, repopulating potential and basal cell-fate commitment of mammary luminal progenitors: implications for basal-like breast cancer. Oncogene 32, pp. 1428-1440. (10.1038/onc.2012.154)
- Smalley, M. J., Piggott, L. and Clarkson, R. W. E. 2013. Breast cancer stem cells: obstacles to therapy. Cancer Letters 338(1), pp. 57-62. (10.1016/j.canlet.2012.04.023)
- Zvelebil, M. et al. 2013. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers. Breast Cancer Research 15(2), article number: R25. (10.1186/bcr3403)
- Eccles, S. A. et al. 2013. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research 15(5), pp. R92. (10.1186/bcr3493)
2012
- Ordonez, L. and Smalley, M. J. 2012. Who do they think they are? Wnt-responsive cells reveal their family trees. Breast Cancer Research 14(6), article number: 327. (10.1186/bcr3351)
- Soady, K. and Smalley, M. J. 2012. Slugging their way to immortality: Driving mammary epithelial cells into a stem cell-like state. Breast Cancer Research 14(5), article number: 319. (10.1186/bcr3188)
- Hopkins, S. et al. 2012. Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis. Developmental Cell 23(3), pp. 547-559. (10.1016/j.devcel.2012.08.001)
- Smalley, M. J. et al. 2012. Isolation of mouse mammary epithelial subpopulations: a comparison of leading methods. Journal of Mammary Gland Biology and Neoplasia 17(2), pp. 91-97. (10.1007/s10911-012-9257-1)
- Regan, J. L., Kendrick, H., Magnay, F., Vafaizadeh, V., Groner, B. and Smalley, M. 2012. c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer. Oncogene 31(7), pp. 869-883. (10.1038/onc.2011.289)
- Milani, E. S. et al. 2012. Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation. Development 140(1), pp. 117-125. (10.1242/dev.082941)
2011
- Wansbury, O. et al. 2011. Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment. Breast Cancer Research 13(4), article number: R79. (10.1186/bcr2928)
- Molyneux, G. and Smalley, M. J. 2011. The cell of origin of BRCA1 mutation-associated breast cancer: a cautionary tale of gene expression profiling. Journal of Mammary Gland Biology and Neoplasia 16(1), pp. 51-55. (10.1007/s10911-011-9202-8)
2010
- Molyneux, G. et al. 2010. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 7(3), pp. 403-417. (10.1016/j.stem.2010.07.010)
- Smalley, M. J. 2010. Isolation, culture and analysis of mouse mammary epithelial cells. In: Ward, A. and Tosh, D. eds. Mouse cell culture : methods and protocols. Methods in Molecular Biology Vol. 633. New York: Springer-Verlag, pp. 139-170., (10.1007/978-1-59745-019-5_11)
- Evers, B. et al. 2010. A tissue reconstitution model to study cancer cell-intrinsic and -extrinsic factors in mammary tumourigenesis. Journal of Pathology 220(1), pp. 34-44. (10.1002/path.2655)
2009
- Bentires-Alj, M., Clarke, R. B., Jonkers, J., Smalley, M. J. and Stein, T. 2009. It's all in the details: methods in breast development and cancer [Meeting Report]. Breast Cancer Research 11(4), article number: 305. (10.1186/bcr2346)
- Grigoriadis, A., Oliver, G., Tanney, A., Kendrick, H., Smalley, M. J., Jat, P. and Neville, A. M. 2009. Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues. BMC Genomics 10(1), article number: 324. (10.1186/1471-2164-10-324)
- Alexander, C. M. et al. 2009. Separating stem cells by flow cytometry: reducing variability for solid tissues. Cell Stem Cell 5(6), pp. 579-583. (10.1016/j.stem.2009.11.008)
- Huser, C. A. et al. 2009. TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival. Cell Death and Differentiation 17(2), pp. 304-315. (10.1038/cdd.2009.126)
- Britt, K. L., Kendrick, H., Regan, J. L., Molyneux, G., Magnay, F., Ashworth, A. and Smalley, M. J. 2009. Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells. Breast Cancer Research 11(2), article number: R20. (10.1186/bcr2245)
2008
- Kendrick, H., Regan, J., Magnay, F., Grigoriadis, A., Mitsopoulos, C., Zvelebil, M. and Smalley, M. J. 2008. Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate. BMC Genomics 9(1), article number: 591. (10.1186/1471-2164-9-591)
- Melchor, L. and Smalley, M. J. 2008. Highway to heaven: mammary gland development and differentiation. Breast Cancer Research 10(5), pp. 305-307. (10.1186/bcr2147)
- Lindeman, G., Visvader, J., Smalley, M. J. and Eaves, C. 2008. The future of mammary stem cell biology: the power of in vivo transplants [Letter]. Breast Cancer Research 10(3), pp. 402. (10.1186/bcr1986)
- Cariati, M., Naderi, A., Brown, J. P., Smalley, M. J., Pinder, S. E., Caldas, C. and Purushotham, A. D. 2008. Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line. International Journal of Cancer 122(2), pp. 298-304. (10.1002/ijc.23103)
- Smalley, M. J., Reis-Filho, J. and Ashworth, A. 2008. BRCA1 and stem cells: tumour typecasting. Nature Cell Biology 10(4), pp. 377-379. (10.1038/ncb0408-377)
2007
- Smalley, M. J. et al. 2007. Regulator of G-protein signalling 2 (RGS2) mRNA is differentially expressed in mammary epithelial subpopulations and overexpressed in the majority of breast cancers. Breast Cancer Research 9(6), article number: R85. (10.1186/bcr1834)
- Molyneux, G., Regan, J. and Smalley, M. J. 2007. Common molecular mechanisms of mammary gland development and breast cancer. Cellular and Molecular Life Sciences 64(24), pp. 3248-3260. (10.1007/s00018-007-7391-5)
- Britt, K., Ashworth, A. and Smalley, M. J. 2007. Pregnancy and the risk of breast cancer. Endocrine-Related Cancer 14(4), pp. 907-933. (10.1677/ERC-07-0137)
- Sleeman, K. E., Kendrick, H., Robertson, D., Isacke, C. M., Ashworth, A. and Smalley, M. J. 2007. Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. Journal of cell biology 176(1), pp. 19-26. (10.1083/jcb.200604065)
- Regan, J. and Smalley, M. J. 2007. Prospective isolation and functional analysis of stem and differentiated cells from the mouse mammary gland. Stem Cell Reviews 3(2), pp. 124-136. (10.1007/s12015-007-0017-3)
2006
- Sleeman, K. E., Kendrick, H., Ashworth, A., Isacke, C. M. and Smalley, M. J. 2006. CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Research 8(R7) (10.1186/bcr1371)
2005
- Smalley, M. J. et al. 2005. Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta. Journal of Cell Science 118(22), pp. 5279-5289. (10.1242/jcs.02647)
- Smalley, M. J., Titley, I. and Ashworth, A. 2005. An improved definition of mouse mammary epithelial side population cells. Cytotherapy 7(6), pp. 497-508. (10.1080/14653240500361145)
- Smalley, M. J. and Clarke, R. B. 2005. The mammary gland “side population”: a putative stem/progenitor cell marker?. Journal of Mammary Gland Biology and Neoplasia 10(1), pp. 37-47. (10.1007/s10911-005-2539-0)
2004
- Ciani, L., Krylova, O., Smalley, M. J., Dale, T. C. and Salinas, P. 2004. A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules. Journal of Cell Biology 164(2), pp. 243-253. (10.1083/jcb.200309096)
2003
- Alvi, A. J. et al. 2003. Functional and molecular characterisation of mammary side population cells. Breast Cancer Research 5(1), pp. R1-R8. (10.1186/bcr547)
- Smalley, M. J. and Ashworth, A. 2003. Stem cells and breast cancer: A field in transit. Nature Reviews Cancer 3, pp. 832-844. (10.1038/nrc1212)
2002
- Fraser, E. et al. 2002. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. Journal of Biological Chemistry 277(3), pp. 2176-2185. (10.1074/jbc.M109462200)
2001
- Smalley, M. J. and Dale, T. C. 2001. Wnt signaling and mammary tumorigenesis. Journal of Mammary Gland Biology and Neoplasia 6(1), pp. 37-52.
- Smalley, M. J., Leiper, K., Tootle, R., McCloskey, P., O'Hare, M. J. and Hodgson, H. 2001. Immortalisation of human hepatocytes by temperature-sensitive SV40 large-T antigen. In Vitro Cellular and Developmental Biology - Animal 37(3), pp. 166-168. (10.1290/1071-2690(2001)037<0166:IOHHBT>2.0.CO;2)
2000
- Webster, M. T. et al. 2000. Sequence variants of the Axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosomes and Cancer 28(4), pp. 443-453. (10.1002/1098-2264(200008)28:4<443::AID-GCC10>3.0.CO;2-D)
- Naylor, S., Smalley, M. J., Robertson, D., Gusterson, B. A., Edwards, P. A. and Dale, T. C. 2000. Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium. Journal of Cell Science 113(12), pp. 2129-2138.
- Sarkar, L., Cobourne, M., Naylor, S., Smalley, M. J., Dale, T. C. and Sharpe, P. T. 2000. Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proceedings of the National Academy of Sciences of the United States of America 97(9), pp. 4520-4524. (10.1073/pnas.97.9.4520)
1999
- Smalley, M. J., Titley, J., Paterson, H., Perusinghe, N., Clarke, C. and O'Hare, M. J. 1999. Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens. Journal of Histochemistry & Cytochemistry 47(12), pp. 1513-1524. (10.1177/002215549904701203)
- Smalley, M. J. and Dale, T. C. 1999. Wnt signalling in mammalian development and cancer. Cancer and Metastasis Reviews 18(2), pp. 215-230. (10.1023/A:1006369223282)
- Smalley, M. J. et al. 1999. Interaction of Axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. EMBO Journal 18(10), pp. 2823-2835. (10.1093/emboj/18.10.2823)
- Smalley, M. J. et al. 1999. Behavior of a cell line derived from normal human hepatocytes on non-physiological and physiological-type substrates: Evidence for enhancement of secretion of liver-specific proteins by a three-dimensional growth pattern. In Vitro Cellular and Developmental Biology - Animal 35(1), pp. 22-32. (10.1007/s11626-999-0040-6)
1998
- Smalley, M. J., Titley, J. and O'Hare, M. J. 1998. Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cellular and Developmental Biology - Animal 34(9), pp. 711-721. (10.1007/s11626-998-0067-0)
Articles
- Williams, J. S. et al. 2024. Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc. Cell & Bioscience 14(38) (10.1186/s13578-024-01206-8)
- Tornillo, G., Warrington, L., Kendrick, H., Higgins, A. T., Hay, T., Beck, S. and Smalley, M. J. 2024. Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model. Disease Models and Mechanisms 17(1), article number: dmm050211. (10.1242/dmm.050211)
- Varney, D. et al. 2023. Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016. Veterinary Record 193(5), article number: e3054. (10.1002/vetr.3054)
- Ordonez, L., Tornillo, G., Kendrick, H., Hay, T. and Smalley, M. J. 2023. NOTCH and AKT signalling interact to drive mammary tumour heterogeneity. Cancers 15(17), article number: 4324. (10.3390/cancers15174324)
- O'Neill, D., Edmunds, G., Urquhart-Gilmore, J., Church, D., Rutherford, L., Smalley, M. and Brodbelt, D. 2023. Dog breeds and conformations predisposed to osteosarcoma in the UK: a VetCompass study. Canine Medicine and Genetics 10, article number: 8. (10.1186/s40575-023-00131-2)
- Edmunds, G., Beck, S., Umakant Kale, K., Spasic, I., O'Neill, D., Brodbelt, D. and Smalley, M. J. 2023. Associations between dog breed and clinical features of mammary epithelial neoplasia in bitches: an epidemiological study of submissions to a single diagnostic pathology centre between 2008-2021. Journal of Mammary Gland Biology and Neoplasia 28(6) (10.1007/s10911-023-09531-3)
- Shorning, B., Trent, N., Griffiths, D. F., Worzfeld, T., Offermanns, S., Smalley, M. J. and Williamson, M. 2023. Plexin-B1 mutation drives metastasis in prostate cancer mouse models. Cancer Research Communications 3(3), pp. 444-458. (10.1158/2767-9764.CRC-22-0480)
- Castro, J. et al. 2021. A nuclear-directed ribonuclease variant targets cancer stem cells and inhibits migration and invasion of breast cancer cells. Cancers 13(17), article number: 4350. (10.3390/cancers13174350)
- Ordonez, L. D. et al. 2021. Reproductive history determines ErbB2 locus amplification, WNT signalling and tumour phenotype in a murine breast cancer model. Disease Models and Mechanisms 14(5), article number: dmm048736. (10.1242/dmm.048736)
- Edmunds, G. L. et al. 2021. Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study. Canine Medicine and Genetics 8, article number: 2. (10.1186/s40575-021-00100-7)
- Pires, A. et al. 2020. Immune remodelling of the extracellular matrix drives loss of cancer stem cells and tumor rejection. Cancer Immunology Research 8(12), pp. 1520 - 1531. (10.1158/2326-6066.CIR-20-0070)
- Regan, J. L. and Smalley, M. J. 2020. Integrating single-cell RNA-sequencing and functional assays to decipher mammary cell states and lineage hierarchies. NPJ Breast Cancer 6, article number: 32. (10.1038/s41523-020-00175-8)
- Shorning, B. Y., Dass, M. S., Smalley, M. J. and Pearson, H. B. 2020. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. International Journal of Molecular Sciences 21(12), article number: 4507. (10.3390/ijms21124507)
- Ordonez, L. D. et al. 2019. Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in Brca2-mutant mammary tumours. Oncotarget 10(27), pp. 2586-2606. (10.18632/oncotarget.26830)
- Mohamed, N., Hay, T., Reed, K. R., Smalley, M. J. and Clarke, A. R. 2019. APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. BMC Cancer 19, article number: 677. (10.1186/s12885-019-5867-y)
- Tornillo, G. et al. 2018. Dual mechanisms of LYN kinase dysregulation drive aggressive behaviour in breast cancer cells. Cell Reports 25(13), pp. 3674-3692. (10.1016/j.celrep.2018.11.103)
- 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)
- Jefferies, M. T. et al. 2017. PTEN loss and activation of K-RAS and β-catenin cooperate to accelerate prostate tumourigenesis. Journal of Pathology 243(4), pp. 442-456. (10.1002/path.4977)
- Chiang, K. et al. 2017. PRMT5 is a critical regulator of breast cancer stem cell function via Histone Methylation and FOXP1 expression. Cell Reports 21(12), pp. 3498-3513. (10.1016/j.celrep.2017.11.096)
- Soady, K. J. et al. 2017. Receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis. Development 144(20), pp. 3777-3788. (10.1242/dev.149120)
- Jardé, T. et al. 2016. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nature Communications 7, article number: 13207. (10.1038/ncomms13207)
- Abraham, T. et al. 2016. Ellipsoid segmentation model for analyzing light-attenuated 3D confocal image stacks of fluorescent multi-cellular spheroids. PLoS ONE 11(6), article number: e0156942. (10.1371/journal.pone.0156942)
- Estrada, M. F. et al. 2016. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. Biomaterials 78, pp. 50-61. (10.1016/j.biomaterials.2015.11.030)
- Ferrari, N. et al. 2015. Runx2 contributes to the regenerative potential of the mammary epithelium. Scientific Reports 5, article number: 15658. (10.1038/srep15658)
- Greenow, K. R. and Smalley, M. J. 2015. Overview of genetically engineered mouse models of breast cancer used in translational biology and drug development. Current Protocols in Pharmacology 70(1), article number: 70:14.36.1-14.36.14. (10.1002/0471141755.ph1436s70)
- Tornillo, G. and Smalley, M. J. 2015. ERrrr..Where are the progenitors? Hormone receptors and mammary cell heterogeneity. Journal of Mammary Gland Biology and Neoplasia 20(1), pp. 63-73. (10.1007/s10911-015-9336-1)
- Francis, J. C. et al. 2015. Whole exome DNA sequence analysis of Brca2 and Trp53 deficient mouse mammary gland tumours. Journal of Pathology 236(2), pp. 186-200. (10.1002/path.4517)
- Iglesias, J. M. et al. 2015. Annexin A8 identifies a subpopulation of transiently quiescent c-Kit positive luminal progenitor cells of the ductal mammary epithelium. Plos One 10(3), article number: e0119718. (10.1371/journal.pone.0119718)
- Soady, K. J. et al. 2015. Mouse mammary stem cells express prognostic markers for triple-negative breast cancer. Breast Cancer Research 17, article number: 31. (10.1186/s13058-015-0539-6)
- Hickman, J. A. et al. 2014. Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo. Biotechnology Journal 9(9), pp. 1115-1128. (10.1002/biot.201300492)
- Melchor, L. et al. 2014. Identification of cellular and genetic drivers of breast cancer heterogeneity in genetically engineered mouse tumour models. Journal of Pathology 233(2), pp. 124-137. (10.1002/path.4345)
- Cowley, M. et al. 2014. Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. PLoS Biology 12(2), pp. e1001799. (10.1371/journal.pbio.1001799)
- Regan, J. et al. 2013. Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner. Cell Reports 4(1), pp. 110-123. (10.1016/j.celrep.2013.05.044)
- Gastaldi, S. et al. 2013. Met signaling regulates growth, repopulating potential and basal cell-fate commitment of mammary luminal progenitors: implications for basal-like breast cancer. Oncogene 32, pp. 1428-1440. (10.1038/onc.2012.154)
- Smalley, M. J., Piggott, L. and Clarkson, R. W. E. 2013. Breast cancer stem cells: obstacles to therapy. Cancer Letters 338(1), pp. 57-62. (10.1016/j.canlet.2012.04.023)
- Zvelebil, M. et al. 2013. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers. Breast Cancer Research 15(2), article number: R25. (10.1186/bcr3403)
- Eccles, S. A. et al. 2013. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research 15(5), pp. R92. (10.1186/bcr3493)
- Ordonez, L. and Smalley, M. J. 2012. Who do they think they are? Wnt-responsive cells reveal their family trees. Breast Cancer Research 14(6), article number: 327. (10.1186/bcr3351)
- Soady, K. and Smalley, M. J. 2012. Slugging their way to immortality: Driving mammary epithelial cells into a stem cell-like state. Breast Cancer Research 14(5), article number: 319. (10.1186/bcr3188)
- Hopkins, S. et al. 2012. Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis. Developmental Cell 23(3), pp. 547-559. (10.1016/j.devcel.2012.08.001)
- Smalley, M. J. et al. 2012. Isolation of mouse mammary epithelial subpopulations: a comparison of leading methods. Journal of Mammary Gland Biology and Neoplasia 17(2), pp. 91-97. (10.1007/s10911-012-9257-1)
- Regan, J. L., Kendrick, H., Magnay, F., Vafaizadeh, V., Groner, B. and Smalley, M. 2012. c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer. Oncogene 31(7), pp. 869-883. (10.1038/onc.2011.289)
- Milani, E. S. et al. 2012. Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation. Development 140(1), pp. 117-125. (10.1242/dev.082941)
- Wansbury, O. et al. 2011. Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment. Breast Cancer Research 13(4), article number: R79. (10.1186/bcr2928)
- Molyneux, G. and Smalley, M. J. 2011. The cell of origin of BRCA1 mutation-associated breast cancer: a cautionary tale of gene expression profiling. Journal of Mammary Gland Biology and Neoplasia 16(1), pp. 51-55. (10.1007/s10911-011-9202-8)
- Molyneux, G. et al. 2010. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 7(3), pp. 403-417. (10.1016/j.stem.2010.07.010)
- Evers, B. et al. 2010. A tissue reconstitution model to study cancer cell-intrinsic and -extrinsic factors in mammary tumourigenesis. Journal of Pathology 220(1), pp. 34-44. (10.1002/path.2655)
- Bentires-Alj, M., Clarke, R. B., Jonkers, J., Smalley, M. J. and Stein, T. 2009. It's all in the details: methods in breast development and cancer [Meeting Report]. Breast Cancer Research 11(4), article number: 305. (10.1186/bcr2346)
- Grigoriadis, A., Oliver, G., Tanney, A., Kendrick, H., Smalley, M. J., Jat, P. and Neville, A. M. 2009. Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues. BMC Genomics 10(1), article number: 324. (10.1186/1471-2164-10-324)
- Alexander, C. M. et al. 2009. Separating stem cells by flow cytometry: reducing variability for solid tissues. Cell Stem Cell 5(6), pp. 579-583. (10.1016/j.stem.2009.11.008)
- Huser, C. A. et al. 2009. TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival. Cell Death and Differentiation 17(2), pp. 304-315. (10.1038/cdd.2009.126)
- Britt, K. L., Kendrick, H., Regan, J. L., Molyneux, G., Magnay, F., Ashworth, A. and Smalley, M. J. 2009. Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells. Breast Cancer Research 11(2), article number: R20. (10.1186/bcr2245)
- Kendrick, H., Regan, J., Magnay, F., Grigoriadis, A., Mitsopoulos, C., Zvelebil, M. and Smalley, M. J. 2008. Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate. BMC Genomics 9(1), article number: 591. (10.1186/1471-2164-9-591)
- Melchor, L. and Smalley, M. J. 2008. Highway to heaven: mammary gland development and differentiation. Breast Cancer Research 10(5), pp. 305-307. (10.1186/bcr2147)
- Lindeman, G., Visvader, J., Smalley, M. J. and Eaves, C. 2008. The future of mammary stem cell biology: the power of in vivo transplants [Letter]. Breast Cancer Research 10(3), pp. 402. (10.1186/bcr1986)
- Cariati, M., Naderi, A., Brown, J. P., Smalley, M. J., Pinder, S. E., Caldas, C. and Purushotham, A. D. 2008. Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line. International Journal of Cancer 122(2), pp. 298-304. (10.1002/ijc.23103)
- Smalley, M. J., Reis-Filho, J. and Ashworth, A. 2008. BRCA1 and stem cells: tumour typecasting. Nature Cell Biology 10(4), pp. 377-379. (10.1038/ncb0408-377)
- Smalley, M. J. et al. 2007. Regulator of G-protein signalling 2 (RGS2) mRNA is differentially expressed in mammary epithelial subpopulations and overexpressed in the majority of breast cancers. Breast Cancer Research 9(6), article number: R85. (10.1186/bcr1834)
- Molyneux, G., Regan, J. and Smalley, M. J. 2007. Common molecular mechanisms of mammary gland development and breast cancer. Cellular and Molecular Life Sciences 64(24), pp. 3248-3260. (10.1007/s00018-007-7391-5)
- Britt, K., Ashworth, A. and Smalley, M. J. 2007. Pregnancy and the risk of breast cancer. Endocrine-Related Cancer 14(4), pp. 907-933. (10.1677/ERC-07-0137)
- Sleeman, K. E., Kendrick, H., Robertson, D., Isacke, C. M., Ashworth, A. and Smalley, M. J. 2007. Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. Journal of cell biology 176(1), pp. 19-26. (10.1083/jcb.200604065)
- Regan, J. and Smalley, M. J. 2007. Prospective isolation and functional analysis of stem and differentiated cells from the mouse mammary gland. Stem Cell Reviews 3(2), pp. 124-136. (10.1007/s12015-007-0017-3)
- Sleeman, K. E., Kendrick, H., Ashworth, A., Isacke, C. M. and Smalley, M. J. 2006. CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Research 8(R7) (10.1186/bcr1371)
- Smalley, M. J. et al. 2005. Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta. Journal of Cell Science 118(22), pp. 5279-5289. (10.1242/jcs.02647)
- Smalley, M. J., Titley, I. and Ashworth, A. 2005. An improved definition of mouse mammary epithelial side population cells. Cytotherapy 7(6), pp. 497-508. (10.1080/14653240500361145)
- Smalley, M. J. and Clarke, R. B. 2005. The mammary gland “side population”: a putative stem/progenitor cell marker?. Journal of Mammary Gland Biology and Neoplasia 10(1), pp. 37-47. (10.1007/s10911-005-2539-0)
- Ciani, L., Krylova, O., Smalley, M. J., Dale, T. C. and Salinas, P. 2004. A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules. Journal of Cell Biology 164(2), pp. 243-253. (10.1083/jcb.200309096)
- Alvi, A. J. et al. 2003. Functional and molecular characterisation of mammary side population cells. Breast Cancer Research 5(1), pp. R1-R8. (10.1186/bcr547)
- Smalley, M. J. and Ashworth, A. 2003. Stem cells and breast cancer: A field in transit. Nature Reviews Cancer 3, pp. 832-844. (10.1038/nrc1212)
- Fraser, E. et al. 2002. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. Journal of Biological Chemistry 277(3), pp. 2176-2185. (10.1074/jbc.M109462200)
- Smalley, M. J. and Dale, T. C. 2001. Wnt signaling and mammary tumorigenesis. Journal of Mammary Gland Biology and Neoplasia 6(1), pp. 37-52.
- Smalley, M. J., Leiper, K., Tootle, R., McCloskey, P., O'Hare, M. J. and Hodgson, H. 2001. Immortalisation of human hepatocytes by temperature-sensitive SV40 large-T antigen. In Vitro Cellular and Developmental Biology - Animal 37(3), pp. 166-168. (10.1290/1071-2690(2001)037<0166:IOHHBT>2.0.CO;2)
- Webster, M. T. et al. 2000. Sequence variants of the Axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosomes and Cancer 28(4), pp. 443-453. (10.1002/1098-2264(200008)28:4<443::AID-GCC10>3.0.CO;2-D)
- Naylor, S., Smalley, M. J., Robertson, D., Gusterson, B. A., Edwards, P. A. and Dale, T. C. 2000. Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium. Journal of Cell Science 113(12), pp. 2129-2138.
- Sarkar, L., Cobourne, M., Naylor, S., Smalley, M. J., Dale, T. C. and Sharpe, P. T. 2000. Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proceedings of the National Academy of Sciences of the United States of America 97(9), pp. 4520-4524. (10.1073/pnas.97.9.4520)
- Smalley, M. J., Titley, J., Paterson, H., Perusinghe, N., Clarke, C. and O'Hare, M. J. 1999. Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens. Journal of Histochemistry & Cytochemistry 47(12), pp. 1513-1524. (10.1177/002215549904701203)
- Smalley, M. J. and Dale, T. C. 1999. Wnt signalling in mammalian development and cancer. Cancer and Metastasis Reviews 18(2), pp. 215-230. (10.1023/A:1006369223282)
- Smalley, M. J. et al. 1999. Interaction of Axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. EMBO Journal 18(10), pp. 2823-2835. (10.1093/emboj/18.10.2823)
- Smalley, M. J. et al. 1999. Behavior of a cell line derived from normal human hepatocytes on non-physiological and physiological-type substrates: Evidence for enhancement of secretion of liver-specific proteins by a three-dimensional growth pattern. In Vitro Cellular and Developmental Biology - Animal 35(1), pp. 22-32. (10.1007/s11626-999-0040-6)
- Smalley, M. J., Titley, J. and O'Hare, M. J. 1998. Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cellular and Developmental Biology - Animal 34(9), pp. 711-721. (10.1007/s11626-998-0067-0)
Book sections
- Smalley, M. J. 2010. Isolation, culture and analysis of mouse mammary epithelial cells. In: Ward, A. and Tosh, D. eds. Mouse cell culture : methods and protocols. Methods in Molecular Biology Vol. 633. New York: Springer-Verlag, pp. 139-170., (10.1007/978-1-59745-019-5_11)
Conferences
- Dimitriou, P., Li, J., Tornillo, G., Smalley, M. and Barrow, D. 2022. Droplet incubator: a new droplet-based model to investigate living cell-synthetic cell interactions. Presented at: MicroTAS 2022, Hangzhou, China, 23-27 October 2022.
Ymchwil
Mae canser yn glefyd heterogenaidd iawn ac mae canser y fron yn enghraifft glasurol o hyn. Mae'r heterogenedd hwnnw i'w ganfod fel heterogenedd rhyng- a mewn-tiwmor. Gellir dosbarthu heterogenedd rhyng-diwmor mewn canser y fron ar sail paramedrau clinigol (e.e. gradd, mynegiant derbynyddion hormonau), proffilio mynegiant genynnau a/neu ddisgrifiad histolegol (mae mwy nag 20 o wahanol is-deipiau histolegol o ganser y fron mewn bodau dynol). Dangosir heterogenedd mewn-tiwmor, mewn cyferbyniad, gan y llu o wahanol fathau o gelloedd a geir mewn tiwmor. Gellir disgrifio'r rhain yn nhermau eu hymddangosiad, e.e. epithelioid, celloedd gwerthyd (tebyg i EMT), squamoid, ond hefyd yn swyddogaethol. Gall celloedd heterogenaidd swyddogaethol fod yn gyfrifol am gynnal y tiwmor cynradd yn ogystal ag am hadu metastases a rhoi ymwrthedd i'r tiwmor i ymyriadau therapiwtig (er na all pob cell ddangos yr holl briodweddau hyn). Yn bwysig, nid oes gan y poblogaethau swyddogaethol hyn hunaniaethau sefydlog, ond gallant godi de novo yn y tiwmor a hefyd esblygu mewn ymateb i bwysau dethol, sy'n cynrychioli targed symudol ar gyfer therapi.
Mewn gwaith blaenorol, fe wnaethom ddefnyddio modelau llygoden o ganser y fron i ymchwilio i sut y gall yr un briwiau genetig sy'n digwydd mewn gwahanol fôn-gelloedd tarddiad effeithio ar heterogeneity canser y fron. Rydym hefyd wedi astudio sut mae gwneud gwahanol briwiau yn yr un gell tarddiad yn actifadu gwahanol rwydweithiau signalau i gynhyrchu gwahanol ffenoteipiau tiwmor. Rydym wedi dangos bod colli'r genyn atal tiwmor Brca1 mewn bôn/cyndeidiau epithelial negyddol derbynnydd estrogen luminal yn y chwarren mamariaidd, ac nid mewn bôn-gelloedd gwaelodol, yn arwain at diwmorau sy'n ffenopïo canserau'r fron BRCA1 dynol a'r mwyafrif o ganserau'r fron nad ydynt yn deuluol fel gwaelodol (Molyneux et al, Cell Stem Cell, 2010). Yn wir, rydym hefyd wedi dangos bod yr un boblogaeth hon yn debygol o fod y gell tarddiad ar gyfer y mwyafrif o ganserau'r fron isel / negyddol (Melchor et al, J Pathology, 2014).
Ein harbenigedd mewn ynysu is-boblogaethau celloedd mamari (Sleeman et al, Breast Cancer Research, 2006; Sleeman et al, J Cell Biol, 2007; Britt et al, Ymchwil Canser y Fron, 2009; Regan et al, Oncogene, 2012) yn ein galluogi i buro bôn-gelloedd mamari i ffwrdd o boblogaethau celloedd mamari eraill, gan gynnwys mathau o gelloedd gwaelodol eraill, a chynnal proffilio moleciwlaidd. Fe wnaethom nodi nifer o enynnau a fynegir yn benodol yn y bôn-gelloedd mamari a dangos bod proffil mynegiant genynnau bôn-gelloedd mamari yn prognostig iawn ar gyfer goroesi heb metastasis mewn cleifion canser y fron triphlyg-negyddol (Sleeman et al, Breast Cancer Research, 2015).
Gan weithio'n fwy mecananyddol, fe wnaethom nodi prosesau allweddol sy'n gysylltiedig â rheoleiddio ymddygiad bôn-gelloedd mamari arferol. Yn dilyn ymlaen o'n dadansoddiad moleciwlaidd manwl o is-boblogaethau celloedd epithelial mamari (Kendrick et al, 2008), fe wnaethom nodi'r rhwydwaith signalau c-KIT fel rheoleiddiwr goroesi ac amlhau rhagflaenydd mamari (Regan et al, Oncogene, 2012). Canfuom hefyd fod y kinase teulu SRC LYN, trawsnewidiwr i lawr yr afon o signalau c-KIT, yn cael ei fynegi mewn rhagflaenwyr mamari arferol ac yn cael ei or-fynegi mewn canserau'r fron tebyg i basal (Molyneux et al, Cell Stem Cell, 2010; Regan et al, Oncogene, 2012). Rydym wedi dangos bod mewn canser y fron sy'n gysylltiedig â cholli swyddogaeth BRCA1, mae gweithgaredd LYN yn cael ei ddatgysylltu rhag actifadu gan c-KIT. Yn hytrach, mae colli BRCA1 yn arwain at uwchreoleiddio isomerase prolyl, PIN1, sy'n rhyngweithio â LYN ac yn actifadu, yn fwyaf tebygol trwy newid ei gydffurfiad i gyflwr gweithredol (Tornillo et al, Cell Reports, 2018). Rydym hefyd wedi dangos bod cydbwysedd isofformiau splice LYN yn cael ei newid mewn canserau'r fron ymosodol, a bod yr isoform hirach, LYN-A, yn hyrwyddo mudo a goresgyniad celloedd canser y fron (Tornillo et al, Cell Reports, 2018). Fodd bynnag, nid oedd gan ddileu genetig LYN mewn celloedd tiwmor o ganser y fron sy'n gysylltiedig â cholli swyddogaeth BRCA1 fawr o wahaniaeth ar ymddygiad tiwmor. Yn hytrach, roedd maint y ymdreiddiad celloedd imiwnedd i'r tiwmor yn rhagfynegydd gwell o ymddygiad tiwmor (Tornillo et al, Disease Models Mechanisms 2024).
Rydym bellach wedi newid ein ffocws i geisio deall beth yw'r ffactorau genetig sy'n rhagdueddol i unigolion gael un math o ganser ac nid un arall, gan ddefnyddio geneteg bridiau cŵn domestig fel system enghreifftiol. Fel cam cyntaf, rydym wedi gweithio gydag oncolegwyr milfeddygol, patholegwyr ac epidemiolegwyr i ddeall y ffenoteipiau brîd sy'n gysylltiedig â gwahanol fathau o ganser, yn enwedig canser mamari cŵn (sy'n fodel ardderchog ar gyfer canser y fron dynol, er gyda rhai rhybuddion) ac osteosarcoma.
Rydym wedi dangos bod risg osteosarcoma yn cynyddu gyda chynnydd mewn màs corff, ond hefyd bod cŵn penglog hir (dolichocephalic) mewn perygl uwch na chŵn wyneb gwastad (brachycephalic) (Edmunds et al, Canine Medicine and Genetics, 2021) (gweler y ffigur isod).
Chwedl Ffigur: Siâp penglog brîd ac OR ar gyfer risg osteosarcoma wedi'i plotio yn erbyn màs cymedrig y corff. Cyfrifwyd màs y corff fel cymedr amcangyfrifon VetCompass o fàs cyfartalog ar gyfer gwrywod a benywod o bob brîd. Ak (u), Akita (Heb ei benodi); AC, Alaskan Malamute; AB, Bulldog Americanaidd; Bydd, Beagle; BF, Bichon Frise; BC, Border Collie; BT, Daeargi Ffin; Bo, Bocsiwr; Bu(u), Bulldog (Heb ei benodi); CT, Daeargi Cairn; CKCS, Cavalier King Charles Spaniel; CS, Cocker Spaniel; Co (u), Collie (Heb ei benodi); Da, Dalmatian; DdB, Dogue de Bordeaux; ESS, Springer Spaniel Saesneg; FT, Daeargi Llwynog; FB, Bulldog Ffrengig; GP(u), Pointer Almaeneg; GSD, ci bugail Almaeneg; GR, Golden Retriever; GD, Great Dane; Gr(u), Greyhound (Heb ei benodi); HV, Vizsla Hwngari; Hu, Husky; JRT, Jack Russell Terrier; La, Labradoodle; LR, Labrador Retriever; Lu, Lurcher; Ma(u), Mastiff (Heb ei benodi); Pi (u), Pinscher (Heb ei benodi); Po(u), Poodle (Heb ei benodi); RR, Rhodesian Ridgeback; Ro, Rottweiler; ST, Daeargi'r Alban; SBT, Daeargi Tarw Swydd Stafford; SP, Poodle Safonol; TT, Daeargi Tibet; Ni, Weimaraner; WHWT, West Highland White Terrier; Wh, Whippet (o Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study. Grace L Edmunds, Matthew J Smalley, Sam Beck, Rachel J Errington, Sara Gould, Helen Winter, Dave C Brodbelt, Dan G O'Neill. Geneteg Med Cŵn, 2021, 8 (1): 2).
Rydym hefyd wedi nodi bridiau sydd â risg uwch o ganser mamari (Varney et al, Veterinary Record, 2023) yn ogystal â darganfod bod brîd nid yn unig yn effeithio ar risg o gael canser ond hefyd ar sut y gall y canser hwnnw ymddwyn, o leiaf ar gyfer tiwmorau mamari (Edmunds et al, Journal of Mammary Gland Biology and Neoplasia, 2023). Gan adeiladu ar ein gwaith blaenorol ar c-KIT, rydym bellach yn astudio a yw etifeddu haploteipiau brîd-benodol o'r genyn KIT yn sail i'r dueddiadau brîd adnabyddus i diwmorau mastgelloedd cŵn, math o diwmor sy'n cael ei yrru gan actifadu afferrant o signalau c-KIT.
Mae ein ffocws presennol hefyd wedi darparu cyfleoedd i weithio gyda chydweithwyr clinigol i nodi a dilysu marcwyr prognostig a rhagfynegol newydd posibl mewn ystod o fathau o diwmor o anifeiliaid cydymaith .
Cymorth grant cyfredol
- Canser y Fron Nawr (2023-2026) - Targedu ymatebion hirdymor i gemotherapi trwy fregusrwydd bôn/imiwnedd newydd mewn Canser y Fron Triphlyg Negyddol (cyd-ymgeisydd gyda'r Athro Richard Clarkson)
Cydweithwyr
- Yr Athro Richard Clarkson (Prifysgol Caerdydd)
- Dr Grace Edmunds (Ysgol Filfeddygol Bryste, Prifysgol Bryste)
- Dr Melanie Dobromylskyj (Patholegwyr y Ffindir)
- Dr Sam Beck (Independent Anatomic Ltd)
- Dr Anita Grigoriadis (Coleg y Brenin Llundain)
- Yr Athro David Brodbelt (Coleg Milfeddygol Brenhinol)
- Dr Dan O'Neill (Coleg Milfeddygol Brenhinol)
Addysgu
Tiwtor personol ar gyfer Israddedigion Gwyddoniaeth Biofeddygol (1af - 4ydd blwyddyn)
Goruchwyliwr Prosiect ar gyfer Prosiectau'r Flwyddyn Olaf Dangradute 3edd Blwyddyn Olaf
Goruchwyliwr Prosiect ar gyfer myfyrwyr Meistr a Meistr Ymchwil Integredig
Goruchwyliwr PhD
Darlithydd - Bioleg Cell (Modiwl 2il Flwyddyn)
Darlithydd - Pynciau Cyfoes mewn Clefydau (Modiwl 3edd Flwyddyn)
Darlithydd - Canser: Mecanweithiau Cellog a Moleciwlaidd a Therapiwteg (Modiwl 3edd Flwyddyn)
Bywgraffiad
Fe wnes i fy ymchwil PhD a hyfforddiant ôl-ddoethurol cynnar yn y Sefydliad Ymchwil Canser, ar safleoedd Sutton a Chelsea, gan weithio ar fioleg datblygiadol mamariaidd. Ar ôl Cymrodoriaeth EMBO blwyddyn yn Sefydliad Canser yr Iseldiroedd yn gweithio gyda'r Athro Anton Berns a'r Athro Jos Jonkers ar fodelau canser llygoden wedi'u haddasu'n enetig, dychwelais i'r ICR fel uwch gymrawd ôl-ddoethurol ac yna arweinydd grŵp iau. Ar y pryd dechreuais fy rhaglen ymchwil i ddefnyddio modelau llygoden i ddeall tarddiad moleciwlaidd a chellog heterogenedd canser y fron, a defnyddio'r wybodaeth honno i nodi targedau therapiwtig moleciwlaidd penodol is-faint canser y fron. Symudais i Ysgol Biowyddorau Caerdydd yn 2012 fel Uwch Ddarlithydd gyda'r Sefydliad Ymchwil Bôn-gelloedd Canser Ewropeaidd (ECSCRI) newydd. Cefais fy dyrchafu'n Ddarllenydd a Dirprwy Gyfarwyddwr ac yna yn Athro yn 2017. Roeddwn i'n Gyfarwyddwr ECSCRI rhwng 2018 a 2022. Ar hyn o bryd rwy'n gweithio ar ddeall gyrwyr genetig rhagdueddiad canser gan ddefnyddio samplau clinigol milfeddygol fel systemau model yn ogystal â datblygu dulliau diagnostig prognostig a rhagfynegol newydd ar gyfer patholeg foleciwlaidd milfeddygol.
Aelodaethau proffesiynol
Aelod o'r Gymdeithas Brydeinig ar gyfer Patholeg Filfeddygol
Safleoedd academaidd blaenorol
Apwyntiadau presennol a blaenorol
2018 – 2022 Cyfarwyddwr, Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop, Prifysgol Caerdydd.
2017 – Athro parhaus , Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop / Ysgol y Biowyddorau, Prifysgol Caerdydd.
2016 – 2017 Cyd-gyfarwyddwr, Cancer Research UK Canolfan Ymchwil Caerdydd.
2015 – 2022 Dirprwy Bennaeth Adran Biofeddygaeth, Ysgol y Biowyddorau, Prifysgol Caerdydd.
2014 – 2017 Darllenydd, Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop / Ysgol y Biowyddorau, Prifysgol Caerdydd.
2013 – 2017 Dirprwy Gyfarwyddwr, Sefydliad Ymchwil Bôn-gelloedd Canser Ewropeaidd.
2012 – 2014 Uwch Ddarlithydd, Sefydliad Ymchwil Bôn-gelloedd Canser Ewrop / Ysgol y Biowyddorau, Prifysgol Caerdydd.
2006 – 2011 Arweinydd Tîm (Cyfadran Ymchwil Datblygu Gyrfa), Canolfan Ymchwil Canser y Fron Breakthrough , Sefydliad Ymchwil Canser, Llundain.
2003 – 2005 Cymrawd Ymchwil Ôl-ddoethurol, Canolfan Ymchwil Canser y Fron Breakthrough , Sefydliad Ymchwil Canser, Llundain.
2002 – 2003 EMBO Cymrodoriaeth Ôl-ddoethurol, Adran Geneteg Moleciwlaidd, Sefydliad Canser yr Iseldiroedd, Amsterdam, Yr Iseldiroedd, Yr Iseldiroedd.
1997 – 2002 Cymrawd Ymchwil Ôl-ddoethurol, Adran Bioleg Celloedd a Moleciwlaidd, Sefydliad Ymchwil Canser, Llundain.
1994 – 1997 Swyddog Ymchwil Ôl-ddoethurol, Ysgol Feddygol Ôl-raddedig Frenhinol, Ysbyty Hammersmith, Llundain.
Cymwysterau
1994 PhD, Bioleg Celloedd, Sefydliad Ymchwil Canser, Llundain.
1990 BA (Anrh, Uwch Ail Ddosbarth), Sŵoleg, Prifysgol Rhydychen.
Pwyllgorau ac adolygu
Cyd-drefnydd Gweithdai EMBO 2017, 2018 a 2020 ar Bioleg Mammary Gland (a gynhaliwyd yn EMBL Heidelberg)
Sefydlydd Rhwydwaith Ewropeaidd Labordai Datblygu Canser a Datblygu Canser (http://www.enbdc.org/)
Aelod o Ymgyrch Canser y Fron/Bwrdd Cynghori Gwyddonol Canser y Fron Nawr (Mai 2012 – Mehefin 2017)
Cyd-gadeirydd Tîm Hunanasesu BIOSI Athena SWAN (hyd at Ebrill 2016; prif awdur ar gais a enillodd Wobr Arian Athena SWAN).
Cynrychiolydd SWAN ar Bwyllgor Staff ac Amgylchedd Gwaith BIOSI (hyd at Ebrill 2016)
Cynrychiolydd ECSCRI ar bwyllgor diogelwch BIOSI (hyd at Ionawr 2016)
Arweinydd academaidd ar y cyd yn Rhwydwaith Bôn-gelloedd Caerdydd (hyd at Ionawr 2016)
Cynrychiolydd BIOSI ar Bwyllgor Lles Anifeiliaid a Gweithdrefnau a Reoleiddir y Coleg Gwyddorau Biolegol a Bywyd (hyd at Ionawr 2016)
Aelod o Fwrdd Golygyddol Ymchwil Canser y Fron (Mawrth 2015 – parhaus)
Aelod o Fwrdd Ymchwil Iechyd Iwerddon – Panel sy'n Canolbwyntio ar Gleifion (Mehefin 2013)
Aelod o Fwrdd Golygyddol y Journal of Mammary Gland Biology and Neoplasia (Mai 2011 - parhaus).
Dirprwy Arweinydd Grŵp 7 (Goresgyniad, Metastasis, Angiogenesis, Hypoxia, Bôn-gelloedd, Celloedd Cylchredeg) o Ddadansoddi Bwlch Ymgyrch Canser y Fron 2012, Hydref 2012.
Gwahodd cyfranogwr (Bioleg – Cychwyn gweithdy arbenigol Canser y Fron), Cyfarfod dadansoddi bwlch Ymgyrch Cancr y Fron, 2 Tachwedd 2006 (Cyhoeddwyd fel A. Thompson, K. Brennan, A. Cox, J. Gee, D. Harcourt, A. Harris, M. Harvie, I. Holen, A. Howell, R. Nicholson, M. Steel a C. Streuli ar ran Cyfarfod Dadansoddi Bwlch Ymgyrch Cancr y Fron, 2 Tachwedd 2006, Llundain, Lloegr (2008). Gwerthusiad o'r cyfyngiadau gwybodaeth cyfredol mewn ymchwil canser y fron: dadansoddiad bwlch. Ymchwil Canser y Fron 10:R36).
Adolygydd llawysgrif ar gyfer Ymchwil Canser y Fron, Ymchwil Cancr, Carcinogenesis, Cell Bôn-gell, Metastasis Clinigol ac Arbrofol, Adolygiadau Arbenigol mewn Meddygaeth Moleciwlaidd, Genes a Datblygu, International Journal of Cancer, Journal of Cell Science, Nature, Nature Reviews Cancer, Oncogene a Bôn-gelloedd
Meysydd goruchwyliaeth
I am interested in supervising PhD students in the areas of:
- Non-DNA repair functions of BRCA1 in breast cancer
- SRC-family kinases in breast cancer
- Veterinary oncology
Note self-funded PhD students must also come with bench fees to support experimental costs
Past projects
Current Students
2019 - 2022 Alex Gibbs (KESS PhD; second supervisor) Cancer stem cells in squamous cell carcinoma
2019 - 2022 Gemma Davies (KESS PhD; second supervisor) CD200 signalling in renal cancer
2018 – 2020 Manisha Das (KESS PhD; second supervisor) PI3K and PTEN signalling in prostate cancer
Previous Students
2016 – 2019 Ana Jiminez Pascual (PhD, second supervisor) FGRF signalling in glioma
2015 – 2017 Maria Konstantinou (PhD, submitted Jan 2018) Theranostic targeting of DNA damage in colo-rectal cancer
2014 – 2017 Noha Mohamed (PhD, awarded 2017) WNT signalling in ovarian cancer
2013 – 2016 Mairian Thomas (PhD, awarded 2016; second supervisor) Novel in vitro mammary cell culture models
2013 – 2014 Huw Morgan (MRes) Novel models of ER+ breast cancer
2009 – 2013 Kelly Soady (PhD, awarded 2013) Identification, purification and molecular characterisation of mammary epithelial stem cells
2006 – 2010 Joseph Regan (PhD, awarded 2010) c-KIT signalling in mammary stem cells
2005 – 2007 Katherine Sleeman (PhD, awarded 2007) Identification of mammary stem and progenitor cell populations
Contact Details
Themâu ymchwil
Arbenigeddau
- Bioleg celloedd canser
- Geneteg canser
- Patholeg filfeddygol
