Dr Robert Clarke PhD

Senior Lecturer

President, International Association for Breast Cancer Research

Associate Editor: Breast Cancer Research and American Journal of Pathology

Service on committees, 2010-2011
President and organiser of the International Association for Breast Cancer Research Conference, Manchester, 2012

http://www.mcrc.manchester.ac.uk/conference/

Organising committee for Breast Cancer Campaign Scientific Conference, London, 18th May, 2010.
Organising Committee for the European Network for Breast Development and Cancer (ENBDC) Workshop, Luzern, Switzerland, April, 2010 & 2011.
Program Organising Committee for the 14th International Congress of Hormonal Steroids and Hormones & Cancer, Edinburgh, Scotland, 2010.
Organising Committee for the 19th International Hormonal Carcinogenesis Meeting, Tokyo, Japan, September, 2010.
Scientific Advisory Committee for the Tenovus Cancer Research Fund, 2009-

Editorial work

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

Editorial Board:
American Journal of Translational Research, 2010-
Journal of Endocrinology, 2007-
Journal of Mammary Gland Biology and Neoplasia, 2005-
Current Stem Cell Research and Therapy, 2005-

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, Hedgehog, Wnt, TGFbeta, EGF pathways and other relevant (eg. 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/

Latest Publications:

Vieira AF, Ricardo S, Ablett M, Farnie G, Cameselle-Teijeiro JF, Seruca R, Schmitt F, Clarke RB and Paredes J (2012) P-cadherin: an adhesion molecule that mediates stem cell properties in basal-like breast cancer. Stem Cells. In press.

Ferraldeschi R, Latif A, Clarke RB, Spence K, Ashton G, O’Sullivan J, Evans DG, Howell A and Newman WG (2012) Lack of Caveolin-1 (P132L) Somatic Mutations in Breast Cancer. Breast Cancer Research and Treatment. In press
 

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

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 at the Paterson Institute for Cancer Research.  I am currently a Senior Lecturer in the School of Cancer and Enabling Sciences in the Paterson Institute for Cancer Research, University of Manchester. 

BSc (Hons), PhD

Lab staff

• Frances Shaw, PhD - CR-UK-funded Postdoctoral Research Associate 
• Rachel Eyre, PhD - Breakthrough Breast Cancer-funded Postdoctoral Research Associate
• Bruno Simoes, PhD - EU FP7-funded Postdoctoral Research Associate
• Denis Alferez, PhD - AstraZeneca-funded Postdoctoral Research Associate
• Kath Spence, BSc - EU FP7-funded Scientific Officer
• Matt Ablett, MRes - BBSRC CASE-funded PhD Student
• Ciara O'Brien, BSc, MRCP - CR-UK-funded PhD Student
• Jagdeep Singh, BSc, MRCP - Royal College of Surgeons-funded MD Clinical Fellow