Contact: c.see@qmul.ac.uk

Professional interests

Our Centre focuses on the links between cancer and inflammation. The overarching hypothesis that drives our research is that the inflammatory mediators and cells found in cancer are more likely to enhance than inhibit tumour progression; hence modulating these cells and mediators will be of therapeutic benefit.

Our aim is to translate our laboratory research in chronic inflammation and the tumour microenvironment into new treatments for cancer, especially ovarian cancer, and we are involved in several Phase I and Phase II clinical trials of cytokine antagonists. We have excellent collaborations with the Departments of Gynaecological Oncology and Medical Oncology at Barts and The London NHS Hospitals.

We also have a strong commitment to public engagement with our work – visit www.centreofthecell.org.

Facilities in the newly refurbished laboratories include:

• Cytokine profiling in human and experimental samples using multiplex systems
• Gene expression arrays
• Expertise in a wide range of mouse models of cancer and of inflammation

Research Groups:

• Cancer and Inflammation
  Prof Frances Balkwill
  Aims to understand links between cancer and inflammation, especially the role of inflammatory cytokines and chemokines and translate this information into novel clinical trials
• Inflammation Biology Group
  Dr Toby Lawrence
  Aims to understand the fundamental mechanisms by which link inflammation and cancer, with particular reference to the role of stromal and inflammatory cells in carcinogenesis.
• Tumour Microenvironment
  Dr Thorsten Hagemann
  Aims to understand the fundamental mechanisms by which TNF-α signalling promotes cancer; with particular reference to the role of macrophages and their phenotype in carcinogenesis.

Research Team:

Kyra Archibald	PhD Student
Dr Magali Bebien	Postdoctoral Research Assistant
Maud Bossard	PhD Student
Juliana Candido	PhD Student
Dr Jermaine Coward	Clinical Fellow
Dr Monica Escorcio-Correia	Postdoctoral Research Assistant
Carol Fong	PhD Student
Zohra Gueroui	Medical Laboratory Assistant
Dr Thorsten Hagemann	Clinical Senior Lecturer
Dr Simon Hallam	Clinical Fellow
Susan Hoare	Senior Scientific Officer
Dr Moddasar Khan	Postdoctoral Research Assistant
Dr Hagen Kulbe	Postdoctoral Research Assistant
Andrew Leinster	PhD Student
Robert Moore	Chief Scientific Officer
Dr Michael Salako	Postdoctoral Research Assistant
Dr Tiziana Schioppa	Postdoctoral Research Assistant
Dr Robin Soper	Postdoctoral Research Assistant
Mr Richard Thompson	Technician

 

Funding:

Cancer Research UK Discovery Committee grant 2009-2011 £204,706 "Generation of Antibodies Against the Chemokine CXCL12 for Cancer Therapy"

Cancer Research UK Programme grant 2008-2013 approx. £1.5m "Targeting Cancer-Related Inflammation"

Cancer Research UK Discovery Committee grant 2008-2010 £159,000 "Targeting the Chemokine Receptor CCR4 in Epithelial Cancer"

Centocor Inc. 2008-2009 $320,000 "Pre-clinical Studies on an Anti-CCL2 Antibody in Ovarian Cancer"

Royal Marsden Hospital Kidney Cancer Research Fund 2007-2008 £56,078 "Support for pre-clinical and clinical studies on Infliximab and Sorafenib"

Cancer Research UK studentship 2006-2010 £118,848 "Inflammatory Cytokines and Malignant Transformation of the Ovarian Surface Epithelium"

Association for International Cancer Research 2006-2009 £201,042 "Targeting CXCR4 and its ligand in ovarian cancer"

Ovarian Cancer Action 2006-2009 £150,000 "Using adenoviruses to target inflammatory cytokines – gene delivery of biological therapies in ovarian cancer"

Medical Research Council Experimental Medicine Award 2006-2009 £585,000 "Cytokine antagonists in ovarian cancer"

Centocor Research Contract. Support for Preclinical and Clinical Studies with Infliximab 2004-2007 £340,000

Recent Publications:

• Hagemann T, Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty S, Thompson RG, Kollias G, Smyth JF, Balkwill FR. The Importance of T cells and IL-17 in the Tumor-Promoting Actions of TNF-a. J Clin Invest 2009;in press.
• Kwong J, Kulbe H, Wong D, Chakravarty P, Balkwill F. An Antagonist of the Chemokine Receptor CXCR4 Induces Mitotic Catastrophe in Ovarian Cancer Cells. Molecular Cancer Therapeutics 2009:8(7);1893-905.
• Kwong J, Chan FL, Wong K-K, Birrer MJ, Archibald KM, Balkwill FR, Berkowitz RS, Mok SC. The Inflammatory Cytokine Tumour Necrosis Factor-Alpha Confers Precancerous Phenotype in An Organoid Model of Normal Human Ovarian Surface Epithelial Cells. Neoplasia 2009:11(6);529-41.
• Li NF, Kocher HM, Salako MA, Obermueller E, Sandle J, Balkwill F. A novel function of colony-stimulating-factor 1 receptor (CSF1R) in hTERT immortalisation of human epithelial cells. Oncogene 2008;28:773-80.
• Hagemann T, McNeish I, Charles KA, Kulbe H, Thompson RC, Robinson SC, Balkwill FR. 'Re-educating' tumor associated macrophages by targeting NF-kB. J Exp Med 2008;205:1261-8.
• Brown ER, Charles KA, Hoare SA, Rye, RL, Jodrell DI, Aird RE, Vora R, Prabhakar Um, Nakada M, Corringham RE, DeWitte M, Sturgeon C, Propper D, Balkwill FR, Smyth JF. A clinical study assessing the tolerability and biological effects of infliximab, a TNF-a inhibitor, in patients with advanced cancer. Annals of Oncology 2008;19:1340-6.
• Karagiannis SN, Bracher MG, Beavil RL, Beavil AJ, Hunt J, McCloskey N, Thompson RG, East N, Burke F, Sutton BJ, Drombrowicz D, Balkwill FR, Gould HJ. Role of IgE receptors in IgE antibody-dependent cytotoxicity and phagocytosis of ovarian tumor cells by human monocytic cells. Cancer Immunol Immunother 2008;57:247-63.
• Karagiannis SN, Bracher MG, Hunt J, McCloskey N, Beavil RL, Beavil AJ, Fear DJ, Thompson RG, East N, Burke F, Moore RJ, Dombrowicz DD, Balkwill FR, Gould HJ. IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J Immunol 2007;179:2832-43.
• Lawrence T, Hagemann T, Balkwill F. Sex, cytokines, and cancer. Science 2007;317:51-2.
• Hagemann T, Balkwill F, Lawrence T. Inflammation and cancer: a double-edged sword. Cancer Cell 2007;12:300-301.
• Li NF, Broad S, Lu YJ, Yang JS, Watson R, Hagemann T, Wilbanks G, Jacobs I, Balkwill F, Dafou D, Gayther SA. Human ovarian surface epithelial cells immortalised with hTERT maintain function prb and p53 expression. Cell Proliferation 2007;40:780-94.
• Harrison ML, Obermueller E, Maisey NR, Hoare S, Edmonds K, Li NF, Chao D, Hall K, Lee C, Timotheadou E, Charles C, Ahern R, King DM, Eisen T, Corringham R, DeWitte M, Balkwill F, Gore M. Tumor necrosis factor α as a new target for renal cell carcinoma: two sequential phase II trials of infliximab at standard and high dose. J Clin Oncol 2007;25:4542-9.
• Hagemann T, Robinson SC, Thompson RG, Payne R, Charles K, Kulbe H, Balkwill FR. Macrophage migration inhibitory factor in epithelial ovarian cancer. Molecular Cancer Therapeutics 2007;6,1193-2002
• Balkwill F. The language of life: how cells communicate in health and disease (Book Review). Nature 2007;435:1162.
• Szlosarek PW, Grimshaw MJ, Wilbanks GD, Hagemann T, Wilson JL, Burke E, Stamp G, Balkwill FR. Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer. Int J Cancer 2007;121:2760-5.
• Kulbe H, Thompson RT, Wilson J, Robinson S, Hagemann T, Fatah R, Gould D, Ayhan A, Balkwill F. The inflammatory cytokine TNF-α generates an autocrine tumour-promoting network in epithelial ovarian cancer cells. Cancer Res 2007;67:585-92.
• Balkwill FR. Guest Editor Special Issue on Cancer and Inflammation. Eur J Cancer 2007;42:689-90.
• Szlosarek P, Charles KA, Balkwill FR. Tumour necrosis factor-alpha as a tumour promoter. Eur J Cancer 2006;42:745-50.
• Szlosarek PW, Klabatsa A, Pallaska A, Sheaff M, Smith P, Crook T, Grimshaw MJ, Steele JP, Rudd RM, Balkwill FR, Fennell DA. In vivo loss of expression of argininosuccinate synthetase in malignant pleural mesothelioma is a biomarker for susceptibility to arginine depletion. Clin Cancer Res 2006;12:7126-31.
• Balkwill F. TNF-α in promotion and progression of cancer. Cancer Metastasis Revs 2006;25:409-16.
• Mantovani A, Balkwill F. RalB signaling: A bridge between inflammation and cancer. Cell 2006;127:42-4.
• Balkwill FR, Ashworth A, Bast RC, Berek JS, Boyd J, Disis ML, Gabra H, Gore ME, Hamilton TC, Jacobs IJ, Kaye SB, Kohn EC, Mills GB, Urban ND. 10th Biennial Helene Harris Memorial Trust meeting. Cancer Res 2006;66:2904-6.
• Hagemann T, Wilson J, Burke F, Kulbe H, Li NF, Pluddemann A, Charles K, Gordon S, Balkwill FR. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 2006;176:5023-32
• Strauss SJ, Maharaj L, Hoare S, Johnson PW, Radford JA, Vinnecombe S, Millard L, Rohatiner A, Boral A, Trehu E, Schenkein DP, Balkwill F, Joel SP. Bortezomib therapy in patients with relapsed or refractory lymphoma: potential correlation of in vitro sensitivity and TNFα response with clinical activity. J Clin Oncol 2006;13:2105-12.
• Szlosarek PW, Grimshaw MJ, Kulbe H, Wilson JL, Wilbanks GD, Burke F, Balkwill FR. Expression and regulation of tumor necrosis factor-α in normal and malignant ovarian epithelium. Mol Cancer Therapy 2006;5:382-90.
• Hagemann T, Balkwill F. MIFed about cancer? Gastroenterology 2005;129:1785-7.
• Madhusudan S, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, Hoare S, Balkwill FR, Ganesan TS. Study of Etanercept, a tumour necrosis factor-alpha inhibitor, in recurrent ovarian cancer. J Clin Oncol 2005;23:5950-9.
• Balkwill F. Immunology for the next generation. Nature Reviews Immunology 2005;5:509-12.
• Kulbe H, Hagermann T, Szlosarek PW, Balkwill FR, Wilson JL. The inflammatory cytokine TNF-α upregulates chemokine receptor expression on ovarian cancer cells. Cancer Res 2005;65:10355-62.
• Hagemann T, Wilson J, Kulbe H, Charles K, Li F, Pukrop T, Trumper L, Binder C, Balkwill FR. TNF-α dependent increased c-Jun and NF-κB activity in tumour cell lines upon co-cultivation with macrophages. J Immunol 2005;175:1197-1205.
• Barton C, Davies D, Balkwill F, Burke F. Involvement of both intrinsic and extrinsic pathways in IFN-γ-induced apoptosis that are enhanced with cisplatin. Eur J Cancer 2005;41:1474-86.
• Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005;7:211-7.
• Jones PH, Christodoulos K, Dobbs N, Thavasu P, Balkwill F, Blann AD, Caine GJ, Kumar S, Kakkar AJ, Gompertz N, Talbot DC, Ganesan TS, Harris AL. Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer. Br J Cancer 2004;91:30-6.
• Balkwill F, Coussens LM. An inflammatory link? Nature 2004;431:405-6.
• Madhusudan S, Foster M, Braybrooke J, Muthuramalingham SR, Wilner S, Kaur K, Han C, Hoare S, Balkwill F, Talbot DC, Ganesan TS, Harris AL. A Phase II study of Etanercept (Enbrel), a tumour necrosis factor-α inhibitor in patients with metastatic breast cancer. Clinical Cancer Research 2004;10:6528-34.
• Scott KA, Arnott CH, Robinson SC, Moore RJ, Thompson RG, Marshall JF, Balkwill FR. TNF-α regulates epithelial expression of MMP-9 and integrin avb6 during tumour promotion. A role for TNF-α in keratinocyte migration? Oncogene 2004;23:6954-66.
• Li NF, Wilbanks G, Balkwill F, Jacobs IJ, Dafou D, Gayther SA. A modified culture medium that significantly improves the growth of human normal ovarian surface epithelial (NOSE) cells in vitro. Lab Invest 2004;84:923-31.
• Hagemann T, Robinson SC, Schulz M, Trumper L, Balkwill FR, Binder C. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-α dependent upregulation of matrix metalloproteases. Carcinogenesis 2004;25:1543-9.
• Grimshaw M, Hagemann T, Ayhan A, Gillett C, Binder C, Balkwill FR. A role for endothelin-2 and its receptors in breast tumor cell invasion. Cancer Research 2004;64:2461-8.
• Arnott CH, Scott KA, Moore RJ, Robinson SC, Thompson RG, Balkwill FR. Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development. Oncogene 2004;23:1902-10.
• Balkwill FR. Cancer and the chemokine network. Nature Reviews Cancer 2004;4:540-50.
• Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Seminars in Cancer Biology 2004;14:171-9.

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