Professor Matthew Smalley
BA (Hons) (Oxon) PhD
Professor
School of Biosciences
- SmalleyMJ@cardiff.ac.uk
- +44 29208 75862
- Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ
Overview
My group is trying to understand how the combination of different tumour-initiating genetic lesions occurring in different normal stem and progenitor cells drives cancer heterogeneity. Working with a variety of model systems, we are interested both in inter-tumour heterogeneity – the clinical differences between tumours – as well as intra-tumour heterogeneity and the response of different cell subsets to selective pressures such as therapy. We are using this information to identify novel therapeutic targets for blocking tumour initiation, growth, therapy resistance and metastasis in different tumour subtypes, with a particular interest in triple-negative breast cancer and the non-DNA repair functions of BRCA1.
We also work closely with vets and veterinary oncologists to study cancer in dogs. Different dog breeds are at risk from different sorts of cancer (for example, English springer spaniels are at increased risk of mammary cancer, compared to crossbreeds, while rottweilers are at increased risk of osteosarcoma) and are therefore an ideal system to identify genetic factors which affect cancer risk. This will not only benefit our understanding of the origins of cancer in general (the comparative oncology or 'One Health' approach) but also directly benefit clinical management of companion animals.
Publication
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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
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
- 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)
- 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., 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)
- 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)
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
- 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)
- 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.
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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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., 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)
- 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)
- 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)
- 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)
- 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.
- 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.
Research
Breast cancer is a highly heterogeneous disease. That heterogeneity is found both as inter- and intra-tumour heterogeneity. Inter-tumour heterogeneity can be classified on the basis of clinical parameters (e.g. grade, expression of hormone receptors), gene expression profiling and/or histological description (there are more than 20 different histological subtypes of breast cancer in humans) and the biological basis for this heterogeneity is largely unknown. If we can understand this, we will not only have a better understanding of the basic biology of tumour development but it will also lead to better patient stratification and the development of targeted therapies for specific tumour subtypes.
Intra-tumour heterogeneity is shown by the multitude of different cell types found within a tumour. These can be described in terms of their appearance, e.g. epithelioid, spindle cells (EMT-like), squamoid, but also functionally. Functionally heterogeneous cells may be responsible for maintaining the primary tumour as well as for seeding of metastases and conferring on the tumour resistance to therapeutic interventions (although not all cells may show all these properties). Importantly, these functional populations do not have fixed identities, but may arise de novo in the tumour and also evolve in response to selective pressures, representing a moving target for therapy.
We are working with different model systems to address these issues. We have used mouse models of breast cancer to investigate how the same genetic lesions occurring in different stem/progenitor cells of origin can affect breast cancer heterogeneity. We have also studied how making different lesions in the same cell of origin activates different signalling networks to generate different tumour phenotypes. We have demonstrated that loss of the Brca1 tumour suppressor gene in luminal estrogen receptor negative epithelial stem/progenitors in the mammary gland, and not in basal stem cells, gives rise to tumours which phenocopy human BRCA1 breast cancers and the majority of non-familial basal-like breast cancers (Molyneux et al, Cell Stem Cell, 2010). Indeed, we have also demonstrated that this same population is likely the cell of origin for the majority of estrogen-receptor low/negative breast cancers (Melchor et al, J Pathology, 2014).
Our expertise in isolation of mammary cell subpopulations (Sleeman et al, Breast Cancer Research, 2006; Sleeman et al, J Cell Biol, 2007; Britt et al, Breast Cancer Research, 2009; Regan et al, Oncogene, 2012) has enabled us to purify mammary stem cells away from other mammary cell populations, including other basal cell types, and carry out molecular profiling. We have identified a number of genes specifically expressed in the mammary stem cells and have demonstrated that the mammary stem cell gene expression profile is highly prognostic for metastasis-free survival in triple-negative breast cancer patients (Sleeman et al, Breast Cancer Research, 2015). We are currently working with clincial collaborators to determine whether this expression profile also predicts response to chemotherapy in these patients,
We are also identifying key processes involved in regulation of normal mammary stem/progenitor cell behaviour. Following on from our detailed molecular analysis of mammary epithelial cell subpopulations (Kendrick et al, 2008), we identified the c-KIT signalling network as a regulator of mammary progenitor survival and proliferation (Regan et al, Oncogene, 2012). We also found that the SRC family kinase LYN, a downstream transducer of c-KIT signalling, is expressed in normal mammary progenitors and over-expressed in basal-like breast cancers (Molyneux et al, Cell Stem Cell, 2010; Regan et al, Oncogene, 2012). We have shown that in BRCA1-loss-of-function-associated breast cancer, LYN activity is uncoupled from activation by c-KIT. Rather, BRCA1 loss results in upregulation of a prolyl isomerase, PIN1, which interacts with and activates LYN, most likely by changing its conformation into an active state (Tornillo et al, Cell Reports, 2018). We have also shown that the balance of splice isoforms of LYN is altered in aggressive breast cancers, and that the longer isoform, LYN-A, promotes breast cancer cell migration and invasion (Tornillo et al, Cell Reports, 2018). We speculate that this effect is a result of altered interactions with the cytoskeleton. We are currently using a mouse genetics approach to confirm the role of LYN in BRCA1-associated breast cancer formation and examining whether blocking LYN function, either by targeting its kinase activity or altering the balance of LYN splice isoforms in a cell, has therapeutic potential.
Most recently we have become interested in companion animal oncology. Cancer is a frequent occurrence in dogs and cats, and in particular mammary cancer is the most frequent cancer of non-neutered female dogs. Interestingly, the histology of canine mammary cancer is much more similer to human breast cancer than is the histology of mouse mammary tumours (although there are some exceptions) and there are also a number of biological similarities, including, for example, some reports that high levels of c-KIT expression and low levels of BRCA1 are associated with malignant canine mammary tumours. Furthermore, different dogs breeds are predisposed to developing different cancer types, offering the opportunity to identify novel genetic risk factors. Therefore, we are now working with veterinary oncologists to apply our expertise in breast cancer models to companion animals, not only to better understand cancer in dogs, and therefore offer new approaches to prevention and treatment, but also as a model for human breast cancer biology,
Current grant support
- Breast Cancer Now (2023-2026) - Targeting long term responses to chemotherapy through a novel stem/immune vulnerability in Triple Negative Breast Cancer (co-applicant with Prof Richard Clarkson)
- Leo Foundation (2020-2023) - Establishing the keratinocyte stem cell basis for skin field cancerisation associated squamous cell carcinoma
- KESS studentships
Collaborators
- Prof Richard Clarkson (Cardiff University)
- Dr Grace Edmunds (Bristol Veterinary School, Bristol University)
- Dr Anita Grigoriadis (Kings College London)
- Dr Maria dM Vivanco (University of Bilbao)
- Dr Tim Robinson (Cardiff and Bristol Universities)
- Professor David Brodbelt (Royal Veterinary College)
- Dr Dan O'Neill (Royal Veterinary College)
Teaching
Personal tutor for Biomedical Science Undergraduates (1st - 4th year)
Project Supervisor for 3rd Year Undergradute Final Year Projects
Project Supervisor for Integrated Masters and Masters of Research Students
PhD Supervisor
Lecturer - Cell Biology (2nd Year Module)
Lecturer - Contemporary Topics in Disease (3rd Year Module)
Lecturer - Cancer: Cellular and Molecular Mechanisms and Therapeutics (3rd Year Module)
Biography
I carried out my PhD research and early postdoctoral training at the Institute of Cancer Research, at both the Sutton and Chelsea sites, working on mammary developmental biology. Following a one year EMBO Fellowship at the Netherlands Cancer Institute working with Prof Anton Berns and Prof Jos Jonkers on genetially modified mouse cancer models, I returned to the ICR as a senior postdoctoral fellow and then a junior group leader. At that time I began my research programme into using mouse models to understand the molecular and (stem) cellular origins of breast cancer heterogeneity, and using that knowledge to identify breast cancer subtype-specific molecular therapeutic targets. I moved to Cardiff School of Biosciences in 2012 as a Senior Lecturer with the new European Cancer Stem Cell Research Institute (ECSCRI). I was promoted to Reader and Deputy Director and then made a Professor in 2017. I was Director of ECSCRI from 2018 - 2022. My work on understand the origins of breast tumour heterogeneity continues, but I now mainly use veterinary clinical samples as model systems.
Professional memberships
Member of the British Society for Veterinary Pathology
Academic positions
Present and previous appointments
2018 – 2022 Director, European Cancer Stem Cell Research Institute, Cardiff University.
2017 – ongoing Professor, European Cancer Stem Cell Research Institute / School of Biosciences, Cardiff University.
2016 – 2017 Co-Director, Cancer Research UK Cardiff Research Centre.
2015 – 2022 Deputy Head of Division of Biomedicine, School of Biosciences, Cardiff University.
2014 – 2017 Reader, European Cancer Stem Cell Research Institute / School of Biosciences, Cardiff University.
2013 – 2017 Deputy Director, European Cancer Stem Cell Research Institute.
2012 – 2014 Senior Lecturer, European Cancer Stem Cell Research Institute / School of Biosciences, Cardiff University.
2006 – 2011 Team Leader (Career Development Research Faculty), The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London.
2003 – 2005 Post-Doctoral Research Fellow, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London.
2002 – 2003 EMBO Post-Doctoral Fellowship, Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
1997 – 2002 Post-Doctoral Research Fellow, Section of Cell and Molecular Biology, The Institute of Cancer Research, London.
1994 – 1997 Post-Doctoral Research Officer, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Qualifications
1994 PhD, Cell Biology, The Institute of Cancer Research, London.
1990 BA (Hons, Upper Second Class), Zoology, Oxford University.
Committees and reviewing
Co-organiser of 2017, 2018 and 2020 EMBO Workshops on Mammary Gland Biology (held at EMBL Heidelberg)
Founder member of the European Network of Breast Development and Cancer Laboratories (http://www.enbdc.org/)
Member of Breast Cancer Campaign/Breast Cancer Now Scientific Advisory Board (May 2012 – June 2017)
Co-Chair of BIOSI Athena SWAN Self-Assessment Team (to April 2016; lead author on application which achieved Athena SWAN Silver Award).
SWAN representative on the BIOSI Staff and Working Environment Committee (to April 2016)
ECSCRI representative on BIOSI safety committee (to January 2016)
Joint academic lead in the Cardiff Stem Cell Network (to January 2016)
BIOSI representative on the College of Biological and Life Sciences Animal Welfare and Regulated Procedures Committee (to January 2016)
Member of the Editorial Board of Breast Cancer Research (March 2015 – ongoing)
Member of Irish Health Research Board – Patient Oriented Panel (June 2013)
Member of the Editorial Board of the Journal of Mammary Gland Biology and Neoplasia (May 2011 - ongoing).
Deputy Group Leader of Group 7 (Invasion, Metastasis, Angiogenesis, Hypoxia, Stem Cells, Circulating Cells) of 2012 Breast Cancer Campaign Gap Analysis, October 2012.
Invited participant (Biology – Initiation of Breast Cancer specialist workshop), Breast Cancer Campaign gap analysis meeting, 2 November 2006 (Published as A. Thompson, K. Brennan, A. Cox, J. Gee, D. Harcourt, A. Harris, M. Harvie, I. Holen, A. Howell, R. Nicholson, M. Steel and C. Streuli on behalf of Breast Cancer Campaign Gap Analysis Meeting, 2 November 2006, London, UK (2008). Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Research 10:R36).
Manuscript reviewer for Breast Cancer Research, Cancer Research, Carcinogenesis, Cell Stem Cell, Clinical and Experimental Metastasis, Expert Reviews in Molecular Medicine, Genes and Development, International Journal of Cancer, Journal of Cell Science, Nature, Nature Reviews Cancer, Oncogene and Stem Cells
Supervisions
I am not currently available to supervise new PhD students.
Research themes
Specialisms
- Cancer cell biology
- Cancer genetics
- Veterinary pathology