Cell Adhesion

BIOGRAPHY

ACADEMIC POSITIONS:
• Director of the Wellcome Trust Centre for Cell-Matrix Research, University of Manchester
• Professor, Faculty of Life Sciences, University of Manchester

EDUCATION AND BACKGROUND:
Charles Streuli obtained his first degree in Biochemistry at the University of Cambridge, and then studied for a PhD degree with David Critchley at the University of Leicester. This was followed by postdoctoral work with Beverly Griffin at the Imperial Cancer Research Fund Laboratories in London (now called the CR-UK London Research Institute), and then Mina Bissell at the Lawrence Berkeley National Laboratory in California. In 1992, Charles was awarded a Senior Research Fellowship in Basic Biomedical Science by the Wellcome Trust to establish his own laboratory at the University of Manchester. Since 2005, he has been engaged with establishing the Manchester Breast Centre, a pan-Manchester organisation that brings together basic and clinical scientists working on mammary gland biology and breast cancer. In 2007, he co-founded and became Research Director of the Breakthrough Breast Cancer Research Unit at the University of Manchester, which is translating discoveries about the causes of early breast cancer to novel prevention and treatment strategies. Charles has also been associated with the Wellcome Trust Centre for Cell-Matrix Research since its inception in the mid-90s, and was appointed to the position of Director of the Cell-Matrix Centre in 2009.

AWARDS, HONORS AND PROFESSIONAL SERVICE:
• 2011-present Cancer Research UK Clinical Scientist Fellowship Panel
• 2010 Keynote Address at the Gordon Research Conference on Mammary Gland Biology
• 2009 Director, Wellcome Trust Centre for Cell-Matrix Research
• 2007-2009 Research Director, Breakthrough Breast Cancer Unit at Manchester
• 2006-2010 Medical Research Council, Molecular and Cellular Medicine Research Board
• 2006 Joint founder, Breakthrough Breast Cancer Unit at Manchester
• 2005 Joint founder, Manchester Breast Centre
• 2004-present Governor, Altrincham Grammar School for Boys
• 2003-present Editorial Board, Organogenesis
• 2001-present Elected to the Committee of the UK Adhesion Society
• 2000-present Associate Editor, Journal of Mammary Gland Biology and Neoplasia
• 2000-present Board of the International Association for Breast Cancer Research
• 2000 Elected to Chair of the Gordon Research Conference on Mammary Gland Biology
• 1999-present Associate Editor, Breast Cancer Research
• 1998-2003 Meetings Secretary, British Society for Cell Biology
• 1992-2002 Wellcome Trust Senior Fellowship in Basic Biomedical Science
• 1990 Fogarty International Fellowship
• 1988-1989 European Molecular Biology Organisation Long Term Fellowship

RESEARCH INTERESTS:
Cell adhesion in epithelial biology and breast cancer

The overall interest of the Streuli laboratory is to determine how cell adhesion to the extracellular matrix (ECM) controls the way that breast epithelial cells work. Integrins are adhesion receptors that bind to ECM proteins on the outside of the cell, and on the inside of the cell they assemble numerous adapter proteins and enzymes into what are known as adhesion complexes. These are mini-organelles situated on the plasma membrane at ECM attachment sites, which both organise the cytoskeleton and control signalling enzymes. The lab is using genetic approaches to determine how integrins control cell-fate decisions in breast epithelial cells. Our recent discoveries include the following:

• Genetic confirmation that integrin-mediated adhesion is necessary for the soluble cytokine prolactin, to initiate its signalling pathway and activate tissue-specific transcription factors in mammary epithelium. The absence of beta1 integrin severely perturbs lactation, thereby demonstrating the importance of ECM adhesion in both the development and the biological function of the breast.
• Identification of integrin-linked kinase and the small GTPase Rac1 as molecular links between integrin and prolactin receptors.
• Demonstration that beta1-integrins are required for establishing and maintaining polarity of epithelial cells in the breast. In the absence of these integrins, luminal cells become disorganised, resembling the dysmorphologies of early breast cancer.
• Discovery that beta1-integrin is required for breast luminal epithelial cells to undergo cell cycle. Other integrins are switched on when the beta1-subunit is deleted, but they are unable to support proliferation. The mechanism may lie in a link between beta1-integrin and the trafficking of the cell cycle regulator, MAP kinase, into the nucleus.
• Discovery that cell-matrix interactions control the internal configuration of nuclei and replication licensing in breast epithelia. These controls are overcome in breast cancer.