Dr Robert Clarke PhD

Photograph of Robert Clarke

Reader in Breast Biology

Breakthrough Breast Cancer Research Unit

Institute of Cancer Sciences
University of Manchester
Manchester Academic Health Science Centre
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX

Role

Former President (2012-2014) and Board Member, International Association for Breast Cancer Research

Associate Editor: American Journal of Pathology (2008-2014) and Breast Cancer Research (2005-2014)

Editorial Board: American Journal of Pathology, Breast Cancer Research and Journal of Mammary Gland Biology and Neoplasia

Memberships of Committees and Professional Bodies

Service on committees

Organising Committee for BACR Breast Cancer Gaps Conference, Newcastle-Gateshead, 2015.

Organising committee for the 7th European Network for Breast Development and Cancer (ENBDC) Workshop, Luzern, Switzerland, April 23-25, 2015.

http://www.enbdc.org/

Member of the British Association for Cancer Research (BACR) Executive Committee, 2012-2015.

Organising Committee for ‘Targeting Notch in Cancer’ Conferences, 2011-2015.

Organising committee for the European Network for Breast Development and Cancer (ENBDC) Workshops, 2009-2015.

Member of Breast Cancer Campaign Tissue Bank Access Committee, 2012-.

Editorial work

Associate Editor:
American Journal of Pathology, 2008-2014
Breast Cancer Research, 2005-2014

Editorial Board: American Journal of Pathology, Breast Cancer Research and Journal of Mammary Gland Biology and Neoplasia.

Research

The goal of our research is to understand the hierarchical relationship between cells in breast epithelium in order to gain an insight into the processes that underlie cancer initiation in this tissue. The primary aim, therefore, is to characterise and to understand the regulation of mammary epithelial stem cells since these are likely to be the targets of cancer-initiating events, and may be the underlying tumourigenic cells in breast cancers. We also wish to understand how steroid hormones such as oestrogen regulate this cellular hierarchy since both normal and tumour development is hormone dependent.

Development of the mammary gland involves the formation of collecting ducts and lobules, both of which are bilayered epithelia made up of contractile myo-epithelial and milk-producing luminal cells. One current interest is which of the Notch, Wnt, TGFbeta, EGF pathways and other relevant (eg. cytokines, Prl, GH and ovarian hormones) signalling pathways regulate stem cell self-renewal. We are also exploiting gene expression arrays, methods for functional genomics and proteomics to identify novel pathways that participate in stem cell regulation.

Identification of stem cell self-renewal pathways may be important for future cancer prevention and therapy. An emerging concept is that in leukemia as well as in neural and epithelial cancers, including breast cancer, only a minority of cells, i.e. the “cancer stem cells”, have the capacity to initiate tumours. Characterising the cancer stem cell and understanding the molecular basis for dysregulated self-renewal is crucial for identification of a) targets for effective therapeutic intervention, and b) those cells in micrometastases which can initiate tumours.

A second theme in the lab is identifying early changes that occur in normal and premalignant tissues and predict the emergence of a tumour. If these changes can be detected and prevented, then it may be possible to reduce the increasing incidence of breast cancer, particularly in the developed Western countries where the lifetime risk of breast cancer now exceeds one in ten women.

The results of these investigations should lead to an increased understanding of the biology of the normal human breast which, in turn, could lead to the development of new strategies or new targets for breast cancer prevention and therapy.

Links:   http://www.breastcentre.manchester.ac.uk/Research

Latest Publications:

Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT, Caldas C, Clarke RB, de Jong S, Jonkers J, Mælandsmo GM, Roman-Roman S, Seoane J, Trusolino L, Villanueva A. Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research. Cancer Discov. 2014 Sep;4(9):998-1013.

Howell A, Anderson AS, Clarke RB, Duffy SW, Evans DG, Garcia–Closas M, Gescher AJ, Key TJ, Saxton JM and Harvie MN (2014) Risk Determination and Prevention of Breast Cancer. Breast Cancer Research, 16:446.

Williams KE, Bundred NJ, Landberg G, Clarke RB and Farnie G (2014) Focal Adhesion Kinase and Wnt signalling regulates human Ductal Carcinoma in Situ stem cell activity and response to radiotherapy. Stem Cells, Sep 3. doi: 10.1002/stem.1843. [Epub ahead of print].

Teaching

Lectures on Cancer Stem Cells in final year BSc Biology and MSc Oncology courses.

Biography

I did my undergraduate BSc studies in Biology at the University of Sussex and the Université de Grenoble.  Following two and half years as a Research Assistant with Professor Potten at the Paterson Institute for Cancer Research, I studied the control of proliferation in the normal and neoplastic human mammary gland for my PhD at The University of Manchester (1995). Subsequently, I undertook post-doctoral training with Dr Liz Anderson in the Clinical Research Department of The Christie, Manchester. I returned to The University of Manchester as a Cancer Research UK Research Fellow in 2001, becoming a Group Leader in the Division of Cancer Studies based at the Paterson Institute for Cancer Research.  I am currently a Reader in Breast Biology in the Breakthrough Breast Cancer Research Unit at the Institute of Cancer Sciences, University of Manchester.

Qualifications

BSc (Hons), PhD

Collaborators and affiliated staff

Lab staff

  • Ahmet Ucar, PhD - Breast Cancer Campaign-funded Senior Postdoctoral Research Associate
  • Rachel Eyre, PhD - Breakthrough Breast Cancer-funded Postdoctoral Research Associate
  • Bruno Simões, PhD - EU FP7-funded Postdoctoral Research Associate
  • Denis Alférez, PhD - Breakthrough Breast Cancer-funded Postdoctoral Research Associate
  • Angélica Santiago Gómez, PhD - Alfonso Martin Escudero Foundation-funded Research Fellow
  • Mohamed Kamal, PhD - Egyptian Government-funded Research Fellow
  • Kath Spence, BSc - EU FP7-funded Senior Scientific Officer
  • Aida Sarmiento Castro, BSc - MRC-funded PhD Student
  • Francesca Chemi, BSc - Visiting PhD Student (University of Calabria, Cosenza, Italy)

Selected publications

2014

  • Ablett MP, O’Brien CS, Sims AH, Farnie G and Clarke RB. (2014). A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity. Oncotarget, 5(3), 599-612. eScholarID:207644
  • Farnie G, Johnson RL, Williams K, Clarke RB, Bundred NJ. (2014). Lapatinib inhibits stem/progenitor proliferation in preclinical in vitro models of ductal carcinoma in situ (DCIS). Cell Cycle, 13(3), 27201. eScholarID:216540
  • Lamb R, Lisanti MP, Clarke RB, Landberg G. (2014). Co-ordination of cell cycle, migration and stem cell-like activity in breast cancer. Oncotarget, 5(17), 7833-7842. eScholarID:230945
  • Vieira AF, Ribeiro AS, Dionísio MR, Sousa B, Nobre R, Albergaria A, Santiago-Gómez A, Schmitt F, Clarke RB, Paredes J. (2014). P-cadherin intracellular signalling is dependent on α6β4 integrin activation inducing stem cell and invasive properties in human breast cancer cells. Oncotarget, 5(3), 679-692. eScholarID:221404

2013

  • Harrison H, Rogerson L, Gregson HJ, Brennan KR, Clarke RB and Landberg G. (2013). Contrasting hypoxic effect on breast cancer stem cell hierarchy is dependent on ERα status. Cancer Research, 73(4), 1420-1433. eScholarID:183505
  • Harrison H, Simões BM, Rogerson L, Howell SJ, Landberg G, Clarke RB. (2013). Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling. Breast Cancer Research, 15, artR21. eScholarID:189572 | DOI:10.1186/bcr3396
  • Lamb R, Ablett MP, Spence K, Landberg G, Sims AH and Clarke RB. (2013). Wnt pathway activity in breast cancer sub-types and stem-like cells. PLoS ONE, 8(7), e67811. eScholarID:201180
  • McClements L, Yakkundi A, Papaspyropoulos A, Harrison H, Ablett MP, Jithesh PV, McKeen HD, Bennett R, Donley C, Kissenpfennig A, McIntosh S, McCarthy HO, O’Neill E, Clarke RB, and Robson T. (2013). Targeting treatment resistant breast cancer stem cells with FKBPL and its peptide derivative, AD-01, via the CD44 pathway. Clinical Cancer Research, 19(14), 3881-3893. eScholarID:201179
  • Singh JK, Farnie G, Bundred NJ, Simões BM, Shergill A, Landberg G, Howell SJ and Clarke RB. (2013). Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms. Clinical Cancer Research, 19(3), 643-656. eScholarID:180333 | DOI:10.1158/1078-0432.CCR-12-1063
  • Singh JK, Simões BM, Howell SJ, Farnie G and Clarke RB. (2013). Recent Advances Reveal IL-8 Signalling as a Potential Key to Targeting Breast Cancer Stem Cells. Breast Cancer Research, 15, 210. eScholarID:207643
  • Yu L, Liu S, Zhang C, Zhang B, Simões BM, Eyre R, Liang Y, Yan H, Wu Z, Guo W, Clarke RB. (2013). Enrichment of human osteosarcoma stem cells based on hTERT transcriptional activity. OncoTarget, 4(12), 2326-2338. eScholarID:216539

2012

  • Ablett MP, Singh JK and Clarke RB. (2012). Stem cells in breast tumours: Are they ready for the clinic? European Journal of Cancer, 48(14), 2104-2116. eScholarID:160735 | DOI:10.1016/j.ejca.2012.03.019
  • Shaw FL, Harrison H, Spence K, Ablett MP, Simões BM, Farnie G, Clarke RB. (2012). A detailed mammosphere assay protocol for the quantification of breast stem cell activity. Journal of Mammary Gland Biology and Neoplasia, 17(2), 111-117. eScholarID:168643 | DOI:10.1007/s10911-012-9255-3
  • Vieira AF, Ricardo S, Ablett MP, Dionísio MR, Mendes N, Albergaria A, Farnie G, Gerhard R, Cameselle-Teijeiro JF, Seruca R, Schmitt F, Clarke RB and Paredes J. (2012). P-Cadherin Is Coexpressed with CD44 and CD49f and Mediates Stem Cell Properties in Basal-like Breast Cancer. Stem Cells, 30(5), 854-864. eScholarID:160736 | DOI:10.1002/stem.1075

2011

  • Agur Z, Kirnasovsky OU, Vasserman G, Tencer-Hershkowicz L, Kogan Y, Harrison H, Lamb R and Clarke RB. (2011). Dickkopf1 Regulates Fate Decision and Drives Breast Cancer Stem Cells to Differentiation: An Experimentally Supported Mathematical Model. PLoS One, 6(9), e24225. eScholarID:155452 | DOI:10.1371/journal.pone.0024225
  • Thompson AM, Quinlan P, Bray SE, Johnson AM, Nikoloff DM, Purdie CA, Jordan LB, Ferraldeschi R, Latif A, Hadfield K, Clarke RB, Ashcroft L, Evans DG, Fontecha M, Hillman G, Howell A, Lawrence HJ and Newman WG. (2011). Comprehensive CYP2D6 genotype, adherence and co-medication affect outcome in breast cancer patients treated with tamoxifen monotherapy. Breast Cancer Research and Treatment, 125(1), 279-287. eScholarID:96492 | DOI:10.1007/s10549-010-1139-x

2010

  • Harrison H, Farnie G, Howell SJ, Rock R, Stylianou S, Brennan KR, Bundred NJ, Clarke RB. (2010). Regulation of breast cancer stem cell activity by signalling through the Notch4 receptor. Cancer Research, 70(2), 709-718. eScholarID:75908 | DOI:10.1158/0008-5472.CAN-09-1681
  • Rieger ME., Sims AH, Coats ER, Clarke RB and Briegel KJ. (2010). The embryonic transcription cofactor LBH is a target of the Wnt signaling pathway in epithelial development and in aggressive basal subtype breast cancers. Molecular and Cellular Biology, 30(17), 4267-4279. eScholarID:87736 | DOI:10.1128/MCB.01418-09

2009

  • Blance RR, Sims A, Anderson E, Howell A-, Clarke RB. (2009). Normal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen. Cancer Prevention Research, 2(3), 257-64. eScholarID:1d32440 | DOI:10.1158/1940-6207.CAPR-08-0161
  • Ong KR, Sims AH, Harvie M, Chapman M, Dunn WB, Broadhurst D, Goodacre R, Wilson M, Thomas N, Clarke RB, Howell A. (2009). Biomarkers of dietary energy restriction in women at increased risk of breast cancer. Cancer Prevention Research, 2(8), 720-731. eScholarID:75907 | DOI:10.1158/1940-6207.CAPR-09-0008

2008

  • Howell SJ, Anderson E, Hunter T, Farnie G, Clarke RB. (2008). Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity. Breast Cancer Res, 10( 4), eScholarID:1d32170 | DOI:10.1186/bcr2129
  • Sims AH, Smethurst GJ, Hey Y, Okoniewski MJ, Pepper SD, Howell A, Miller CJ, Clarke RB. (2008). The removal of multiplicative, systematic bias allows integration of breast cancer gene expression datasets - improving meta-analysis and prediction of prognosis. BMC Med Genomics, 1( 1), eScholarID:1d32394 | DOI:10.1186/1755-8794-1-42

2007

  • Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson N, Bundred NJ. (2007). Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst, 99(8), 616-627. eScholarID:1d15720 | DOI:10.1093/jnci/djk133

View all publications