Professor Claire Lewis
Department of Oncology and Metabolism
Professor of Molecular & Cellular Pathology
Research Director, Weston Park Cancer Centre
Visiting Professor, Leiden University, The Netherlands
+44 114 215 9012
Full contact details
Department of Oncology and Metabolism
The Medical School
Beech Hill Road
After completing my DPhil (PhD) in the Department of Physiology, Anatomy and Genetics in Oxford in 1986, I held two postdoctoral positions and a Lectureship in the Medical School there before moving to join the Medical School in Sheffield in 1996.
I currently hold a Personal Chair in Molecular & Cellular Pathology and head a team of pre and postdoctoral scientists in the Academic Unit of Inflammation and Tumour Targeting.
I was awarded a DSc by Oxford University in 2006 for my contribution to the field of tumour inflammation research.
- Research interests
Our research is focused mainly on the role of inflammatory cells called macrophages in tumour progression and responses to conventional anti-cancer treatments like chemotherapy and irradiation.
We have also developed ways of using these cells to target therapeutic genes and viruses to tumours. Our work was reported in the national press (http://www.bbc.co.uk/news/health-20795977,) and is mainly funded by grants from Breast Cancer Now, Prostate Cancer UK, The European Union, Cancer Research UK and Team Verrico.
- Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis.. Oncogene. View this article in WRRO
- The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials, 198, 180-193. View this article in WRRO
- Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nature Cell Biology, 21, 190-202. View this article in WRRO
- Diverse functions of macrophages in different tumor microenvironments. Cancer Research, 78(19), 5492-5503. View this article in WRRO
- Perivascular macrophages in health and disease. Nature Reviews Immunology, 18(11), 689-702. View this article in WRRO
- The Multifaceted Role of Perivascular Macrophages in Tumors. Cancer Cell, 30(1), 18-25. View this article in WRRO
- Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy. Cancer Research, 75(17), 3479-3491.
- Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting. Nature Communications, 6. View this article in WRRO
- Development of a Trojan horse oncolytic virus for treatment of myeloma.. Journal of Clinical Oncology, 33(15_suppl), e14035-e14035.
- Classification of current anticancer immunotherapies. Oncotarget, 5(24), 12472-12508. View this article in WRRO
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- Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain. Journal of Aging Science, 2(1). View this article in WRRO
- A peptide derived from TIMP-3 inhibits multiple angiogenic growth factor receptors and tumour growth and inflammatory arthritis in mice.. Angiogenesis, 17(1), 207-219. View this article in WRRO
- Macrophage Regulation of Tumor Responses to Anticancer Therapies. CANCER CELL, 23(3), 277-286.
- Construction of Human Monocyte Derived Macrophages Armed with Oncolytic Viruses. BIO-PROTOCOL, 3(13).
- Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis after chemotherapy or irradiation.. Cancer Res, 73(2), 490-495.
- Generation of a novel mouse model for the inducible depletion of macrophages in vivo.. Genesis, 51(1), 41-49.
- CANCER Macrophages limit chemotherapy. NATURE, 472(7343), 303-304.
- Abstract 2849: Tie2-expressing macrophages (TEM) depletion may enhance the clinical efficacy of combretastatin A-4-phosphate (CA-4-P). Tumor Biology.
- Multiple effects of angiopoietin-2 blockade on tumors.. Cancer Cell, 19(4), 431-433.
- TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice.. J Clin Invest, 121(5), 1969-1973.
- Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion.. J Immunol, 186(7), 4183-4190.
- Mathematical modeling predicts synergistic antitumor effects of combining a macrophage-based, hypoxia-targeted gene therapy with chemotherapy.. Cancer Res, 71(8), 2826-2837.
- Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth.. Int J Cancer, 129(4), 847-858.
- Use of macrophages to target therapeutic adenovirus to human prostate tumors.. Cancer Res, 71(5), 1805-1815.
- New insights into induction of early-stage neovascularization in an improved tissue-engineered model of psoriasis. Journal of Tissue Engineering and Regenerative Medicine, 5(5), 363-374.
- NF-κB as a central regulator of macrophage function in tumors.. J Leukoc Biol, 88(5), 877-884.
- Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions.. Cancer Res, 70(13), 5270-5280.
- Elusive identities and overlapping phenotypes of proangiogenic myeloid cells in tumors.. Am J Pathol, 176(4), 1564-1576.
- A novel fragment derived from the beta chain of human fibrinogen, beta43-63, is a potent inhibitor of activated endothelial cells in vitro and in vivo.. Br J Cancer, 102(3), 594-601. View this article in WRRO
- Tumor-associated macrophages: effectors of angiogenesis and tumor progression.. Biochim Biophys Acta, 1796(1), 11-18.
- Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia.. Blood, 114(4), 844-859.
- Neutrophils: key mediators of tumour angiogenesis.. Int J Exp Pathol, 90(3), 222-231.
- Regulation of macrophage function in tumors: the multifaceted role of NF-kappa B. BLOOD, 113(14), 3139-3146.
- Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.. Gene Ther, 16(3), 329-339.
- Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways.. Stroke, 40(2), 369-375.
- The role of myeloid cells in the promotion of tumour angiogenesis.. Nat Rev Cancer, 8(8), 618-631.
- Hypoxia-induced secretion of macrophage migration-inhibitory factor from MCF-7 breast cancer cells is regulated in a hypoxia-inducible factor-independent manner. CANCER LETT, 265(2), 239-249.
- A novel magnetic approach to enhance the efficacy of cell-based gene therapies.. Gene Ther, 15(12), 902-910.
- Plasticity of macrophage function during tumor progression: Regulation by distinct molecular mechanisms. J IMMUNOL, 180(4), 2011-2017.
- Research alert: Gene therapy - Microscopic magnets attached to human cells offer hope for cancer treatment. Biomedical Materials(JUNE), 10.
- Plasticity in tumor-promoting inflammation: Impairment of macrophage recruitment evokes a compensatory neutrophil response. Neoplasia, 10(4), 329-339.
- Effects of hypoxia on transcription factor expression in human monocytes and macrophages.. Immunobiology, 213(9-10), 899-908.
- Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. TRENDS IMMUNOL, 28(12), 519-524.
- Microglial activation in white matter lesions and nonlesional white matter of ageing brains.. Neuropathol Appl Neurobiol, 33(6), 670-683.
- Preface. Angiogenesis Assays: A Critical Appraisal of Current Techniques.
- Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2.. Cancer Res, 67(18), 8429-8432.
- White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses.. Neuropathol Appl Neurobiol, 33(4), 410-419.
- Macrophage-based anti-cancer therapy: Modelling different modes of tumour targeting. B MATH BIOL, 69(5), 1747-1776.
- Expression of Tie-2 by human monocytes and their responses to angiopoietin-2.. J Immunol, 178(11), 7405-7411.
- Identification of key residues involved in mediating the in vivo anti-tumor/anti-endothelial activity of Alphastatin.. J Thromb Haemost, 5(4), 846-854.
- Inflammation and breast cancer. Microenvironmental factors regulating macrophage function in breast tumours: hypoxia and angiopoietin-2.. Breast Cancer Res, 9(3), 209. View this article in WRRO
- White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury.. Stroke, 37(6), 1391-1398.
- Gene therapy for prostate cancer: current strategies and new cell-based approaches.. Prostate, 66(5), 470-494.
- Macrophages promote angiogenesis in human breast tumour spheroids in vivo.. Br J Cancer, 94(1), 101-107. View this article in WRRO
- Distinct role of macrophages in different tumor microenvironments.. Cancer Res, 66(2), 605-612.
- Expression of vascular endothelial growth factor and its receptors in the central nervous system in amyotrophic lateral sclerosis.. J Neuropathol Exp Neurol, 65(1), 26-36.
- Use of bacteria in anti-cancer therapies.. Bioessays, 28(1), 84-94.
- Macrophage migration and gene expression in response to tumor hypoxia.. Int J Cancer, 117(5), 701-708.
- Hypoxia regulates macrophage functions in inflammation.. J Immunol, 175(10), 6257-6263.
- Macrophage Responses to Hypoxia. The American Journal of Pathology, 167(3), 627-635.
- Screening of the regulatory and coding regions of vascular endothelial growth factor in amyotrophic lateral sclerosis. NEUROGENETICS, 6(2), 101-104.
- Angiogenesis inhibitors found within the haemostasis pathway.. J Cell Mol Med, 9(2), 286-302.
- Biological inferences from a mathematical model of comedo ductal carcinoma in situ of the breast.. J Theor Biol, 232(4), 523-543.
- Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues.. Blood, 104(8), 2224-2234.
- Vascular endothelial growth factor and the nervous system. Neuropathology and Applied Neurobiology, 30(5), 427-446.
- Current methods for assaying angiogenesis in vitro and in vivo.. Int J Exp Pathol, 85(5), 233-248.
- OC9 ALPHASTATIN, A 24-AMINO ACID FRAGMENT OF FIBRINOGEN IS A NOVEL ANTI-ANGIOGENIC AND ANTI-VASCULAR AGENT. Microcirculation, 11(6), 531-532.
- PC41 THE IN VIVO EFFICACY OF THE ANTIANGIOGENIC PEPTIDE ALPHASTATIN. Microcirculation, 11(6), 552-553.
- Anoxic induction of ATF-4 through HIF-1-independent pathways of protein stabilization in human cancer cells. BLOOD, 103(5), 1876-1882.
- Mathematical modelling of the use of macrophages as vehicles for drug delivery to hypoxic tumour sites. J THEOR BIOL, 226(4), 377-391.
- Alphastatin, a 24-amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo.. Blood, 103(2), 601-606.
- The transcription factors hypoxia-inducible factor 1 alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. ARTHRITIS RHEUM, 50(1), 291-296.
- Hemostatic regulators of tumor angiogenesis: a source of antiangiogenic agents for cancer treatment?. J Natl Cancer Inst, 95(22), 1660-1673.
- Modelling the early growth of ductal carcinoma in situ of the breast. J MATH BIOL, 47(5), 424-452.
- The role of fibrinogen and related fragments in tumour angiogenesis and metastasis.. Expert Opin Biol Ther, 3(7), 1105-1120.
- Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy.. Am J Pathol, 163(4), 1233-1243.
- Mathematical modelling of comedo ductal carcinoma in situ of the breast. MATH MED BIOL, 20(3), 277-308.
- A multiphase model describing vascular tumour growth. B MATH BIOL, 65(4), 609-640.
- Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1.. Br J Cancer, 87(10), 1173-1181. View this article in WRRO
- Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. J LEUKOCYTE BIOL, 72(3), 417-428.
- Expression of hypoxia inducible factor-1 in metastatic tumour's in ovarian cancer: link with p53 expression and relevance to hypoxia-targeted gene therapies for disseminated disease. J PATHOL, 198, 5A-5A.
- The role of cell-cell interactions in a two-phase model for avascular tumour growth. J MATH BIOL, 45(2), 125-152.
- Fibrinogen E fragment selectively disrupts the vasculature and inhibits the growth of tumours in a syngeneic murine model.. Br J Cancer, 86(11), 1813-1816. View this article in WRRO
- The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies.. J Pathol, 196(3), 254-265.
- Expression of HIF-1alpha by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy.. J Pathol, 196(2), 204-212.
- Modelling macrophage infiltration into avascular tumours. Journal of Theoretical Medicine, 4(1), 21-39.
- View this article in WRRO Modelling the interactions between tumour cells and a blood vessel in a microenvironment within a vascular tumour. EUR J APPL MATH, 12, 529-556.
- Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors.. J Leukoc Biol, 70(4), 478-490.
- Hypoxic Upregulation of TNF Receptor Type 2 Expression Involves NF-IL-6 and Is Independent of HIF-1 or HIF-2. Journal of Interferon & Cytokine Research, 21(9), 757-762.
- Hypoxic macrophages accumulate in avascular, hypoxic areas of prostate cancer and benign prostatic hyperplasia.. J PATHOL, 195, 33A-33A.
- Expression of hypoxia-inducible factor la by macrophages in the rheumatoid synovium - Implications for targeting of therapeutic genes to the inflamed joint. ARTHRITIS RHEUM, 44(7), 1540-1544.
- Estimating the selective advantage of mutant p53 tumour cells to repeated rounds of hypoxia. B MATH BIOL, 63(1), 135-166.
- Fibrin fragment E stimulates the proliferation, migration and differentiation of human microvascular endothelial cells in vitro.. Angiogenesis, 4(4), 269-275.
- Comparison of three in vitro human 'angiogenesis' assays with capillaries formed in vivo.. Angiogenesis, 4(2), 113-121.
- Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas.. J Pathol, 192(2), 150-158.
- The role of p53 gene status in modulating the effects of hypoxia on human epithelial ovarian cancer cells. J PATHOL, 192, 10A-10A.
- Macrophage expression of urokinase receptors correlates with macrophage infiltration and angiogenesis in invasive carcinoma of the breast: Regulation by hypoxia. J PATHOL, 192, 20A-20A.
- Macrophages accumulate in avascular, hypoxic areas of prostate tumours: implications for targeted therapeutic gene delivery to such sites.. J PATHOL, 192, 8A-8A.
- Fibrinogen E-fragment inhibits the migration and tubule formation of human dermal microvascular endothelial cells in vitro.. Cancer Res, 60(17), 4719-4724.
- Characterisation of hypoxia responsive element activity under anoxia in breast cancer cells: Role of HIF-1 and ATF-4. BRIT J CANCER, 83, 11-11.
- Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J PATHOL, 190(4), 430-436.
- The macrophage – a novel system to deliver gene therapy to pathological hypoxia. Gene Therapy, 7(3), 255-262.
- Macrophage responses to hypoxia: relevance to disease mechanisms.. J Leukoc Biol, 66(6), 889-900.
- View this article in WRRO Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. BRIT J CANCER, 79(5-6), 991-995.
- The Macrophage-Exploiting Hypoxia With Cell Based Delivery of GDEPT. Nature Biotechnology, 17(S4), 38-38.
- Regulation of angiogenesis in ovarian cancer: role of p53, vascular endothelial growth factor and hypoxia.. J PATHOL, 189, 16A-16A.
- Expression of vascular endothelial growth factor by macrophages is upregulated in poorly vascularised areas of breast carcinomas. J PATHOL, 189, 13A-13A.
- Validation of anti-vascular endothelial growth factor (anti-VEGF) antibodies for immunohistochemical localization of VEGF in tissue sections: Expression of VEGF in the human endometrium. J PATHOL, 185(4), 402-408.
- Association of tumour necrosis factor and its receptors with thymidine phosphorylase expression and metastasis in human breast cancer. J PATHOL, 182, A16-A16.
- View this article in WRRO Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma. BRIT J CANCER, 77(12), 2246-2251.
- Response of tumour cells to hypoxia: role of p53 and NFkB.. Mol Pathol, 51(2), 55-61.
- Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Research, 56(20), 4625-4629.
- ALTERED EXPRESSION OF TGFα AND TGFβ1 IN THE MUCOSA OF THE FUNCTIONING PELVIC ILEAL POUCH. The Journal of Pathology, 180(4), 407-414.
- Non-isotopic in situ detection of mRNA for interleukin-4 in archival human tissue. Journal of Immunological Methods, 167(1-2), 47-54.
- Cytokine networks in solid human tumors: regulation of angiogenesis. Journal of Leukocyte Biology, 56(4), 423-435.
- Expression of tumour necrosis factor α and its receptors in carcinoma of the breast. British Journal of Cancer, 70(2), 289-292.
- Tumour-associated leucocytes: Friends or foes in breast carcinoma. The Journal of Pathology, 172(3), 229-235.
- Secretion of epidermal growth factor by macrophages associated with breast carcinoma. The Lancet, 342(8864), 148-149.
- Growth factors: Regulation of normal and neoplastic growth. The Journal of Pathology, 169(2), 191-201.
- Growth arrest of the breast cancer cell line, T47D, by TNF α; cell cycle specificity and signal transduction. British Journal of Cancer, 67(2), 290-296.
- Epidermal growth factor, insulin-like growth factor-1 and basic fibroblast growth factor modulate the cytostatic effect of tumour necrosis factor-α on the breast cancer cell line, T47D. Cytokine, 5(2), 169-172.
- Effect of major surgery on the release of interferon gamma by peripheral blood mononuclear cells: An investigation at the single cell level using the reverse haemolytic plaque assay. Cytokine, 4(1), 63-65.
- Detecting cytokine production at the single-cell level. Cytokine, 3(3), 184-188.
- Cytokine Release by Single, Immunophenotyped Human Cells: Use of the Reverse Hemolytic Plaque Assay. Immunological Reviews, 119(1), 23-39.
- Human tumour-associated NK cells secrete increased amounts of interferon-γ and interleukin-4. British Journal of Cancer, 64(3), 457-462.
- Basic fibroblast growth factor and interleukins 4 and 6 stimulate the release of IFN-γ by individual NK cells. Cellular Immunology, 132(1), 158-167.
- Measurement of cytokine release by human cells A quantitative analysis at the single cell level using the reverse haemolytic plaque assay. Journal of Immunological Methods, 127(1), 51-59.
- Differential effects of LPS, IFN-γ and TNFα on the secretion of lysozyme by individual human mononuclear phagocytes: Relationship to cell maturity. Immunology, 69(3), 402-408.
- Effects of ethanol on human monocyte/macrophage lysozyme storage and release. Journal of Hepatology, 10(1), 90-98.
- Heterogeneity of responses to LH-releasing hormone and phorbol ester among rat gonadotrophs: a study using a reverse haemolytic plaque assay for LH. Journal of Molecular Endocrinology, 2(1), 55-63.
- Heterogeneity among human mononuclear phagocytes in their secretion of lysozyme, interleukin 1 and type-β transforming growth factor: a quantitative analysis at the single-cell level. European Journal of Immunology, 19(11), 2037-2043.
- Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat B cells. Molecular and Cellular Endocrinology, 57(1-2), 41-49.
- DIABETES-ASSOCIATED PEPTIDE. The Lancet, 330(8565), 966-966.
- ISLET AMYLOID FORMED FROM DIABETES-ASSOCIATED PEPTIDE MAY BE PATHOGENIC IN TYPE-2 DIABETES. The Lancet, 330(8553), 231-234.
- Multiple injections of LH-releasing hormone into hypogonadal (hpg) mice induce the appearance of two morphologically distinct populations of gonadotrophs. Journal of Endocrinology, 111(3), 483-NP.
- Hyperprolactinemia Induced by Pituitary Isografts Suppresses the Priming Effect of LH-Releasing Hormone in Normal and Hypogonadal Mice. Neuroendocrinology, 43(5), 584-589.
- Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro. Journal of Endocrinology, 109(1), 35-NP.
- The role of microfilaments in the priming effect of LH-releasing hormone: an ultrastructural study using cytochalasin B. Journal of Endocrinology, 106(2), 211-NP.
- Alphastatin: a pluripotent inhibitor of activated endothelial cells In Siemann DW (Ed.), Vascular-targeted therapies in oncology (pp. 205-220). Wiley-Blackwell
Conference proceedings papers
- Engineering macrophages to synthesize recombinant adenoviruses in hypoxic areas of human prostate tumors. CANCER RESEARCH, Vol. 66(8)
- Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. Journal of Leukocyte Biology, Vol. 57(5) (pp 747-751)
- Research group
Members of the AUITT
- Professor Claire Lewis
- Dr Munitta Muthana (Senior Lecturer)
- Dr Mohammed Ridha (Postdoc)
- Dr Haider Al-Janabi (Postdoc)
- Dr Jenny Down (Postdoc)
- Dr Xuan Pu (Postdoc)
- Dr Faith Howard (Postdoc)
- Dr Amy Kwan (Clinical Research Fellow & PhD Student)
- Christine Hospach (ECR & PhD Student)
- Richard Allen (PhD Student)
- Areej Alghamdi (PhD Student)
- Natalie Winder (PhD Student)
- Rita Dey (SHU Placement Student)
- Teaching interests
- Acute and chronic inflammation
- Angiogenesis in human diseases
- Professional activities
- Member of the Editorial Board, Cancer Research.
- Member of the Editorial Board, Journal of Clinical Investigation Insight.
- Member of the Editorial Board, OncoImmunology.
- Member of the Editorial Board, International Journal of Cancer.
- Associate Editor, International Journal of Experimental Pathology.
Grant Awarding Bodies
- Member, MRC Molecular & Cellular Medicines Board (April 2018 onwards).
- Member, PCUK Research Advisory Committee (October 2019 onwards).
- Member, Quinquennial Review Panel, MRC Human Immunology Unit, Oxford, Nov. 2016.
- Member, Quinquennial Review Panel, Breast Cancer Now Manchester Research Unit, Feb. 2016.
- Member, Senior Investigator Awards Committee, The Wellcome Trust, (2013).
- Member of 3 Scientific Advisory Boards: ‘Cancer Immunotherapy’, Tumour Inflammation’ and ‘Metastasis’ for the Cancer Section of EU Framework 7 (2007- present).
- Member, International Science Evaluation Panel (for biology, medicine and health), The Research Council, Norway (2011).
- Member, AACR Basic Cancer Research Grants Scientific Review Committee (2010).
- Chair, BBSRC Review Panel in Interdisciplinary Research (2005).
- MRC College of Experts - Molecular and Cellular Medicine Board, (2004-current).
- EPSRC Peer Review College (2006-2009).
- Member, Scientific Advisory Board, Breast Cancer Campaign (1999-2002)