Dr Richard Morgan
Senior Lecturer in Molecular Oncology
Qualifications: BSc PhD
Phone: Work: 01483 68 8618
Room no: 29 PGM 02
9am to 5pm Mon-Fri
BA Hons. in Natural Sciences - Chemistry, Biochemistry, Maths and Statistics (2i). University of Cambridge 1990.
Ph.D. in Biochemistry - University of Birmingham 1993.
June 2000-January 2006 Tenure track research scientist, Department of Basic Medical Sciences, St. George’s Hospital Medical School, London
1997-2000 Post doctoral scientist - The Hubrecht Laboratory for Developmental Biology, Utrecht, The Netherlands
1993-1997 Post doctoral scientist - National Institute for Medical Research, London
1990-1993 Post graduate student - ICI Pharmaceuticals, Cheshire.
Richard Morgan is studying the potential of transcription factors as targets and biomarkers in cancer, particularly the HOX / Engrailed family of homeodomain containing transcription factors. For the former, work starting in 2004 gave rise to a series of reagents that block HOX function and have proved to be potent, first in class, anti-cancer molecules (Morgan et al., 2007; Shears et al., 2008; Plowright et al., 2009; Morgan et al., 2010; Daniels et al., 2010).
In addition, the group is also investigating the potential of HOX and Engrailed transcription factors as biomarkers for the diagnosis of a number of cancers including that of the prostate, lung and bladder. Their most recent publication (Morgan et al., 2011) identifies the EN2 transcription factor as a diagnostic marker for prostate cancer with twice the sensitivity of the currently used marker, PSA. EN2 is now undergoing clinical trials at multiple, international centres.
- 'Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma'. Cancer Chemotherapy and Pharmacology, 73 (1), pp. 53-60. . (2014)
- 'EN2: a novel prostate cancer biomarker.'. Biomark Med, England: 7 (6), pp. 893-901.doi: 10.2217/bmm.13.115
- 'The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway'. International Journal of Cancer, 133 (4), pp. 879-892.doi: 10.1002/ijc.28097
- 'Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker'. European Journal of Cancer, 49 (9), pp. 2214-2222. . (2013)
- 'The role of HOX genes in normal hematopoiesis and acute leukemia'. Leukemia, 27 (5), pp. 1000-1008.doi: 10.1038/leu.2012.356
- 'Engrailed homeobox transcription factors as potential markers and targets in cancer'. FEBS Letters, 587 (6), pp. 549-554. . (2013)
- 'Engrailed homeobox transcription factors as potential markers and targets in cancer.'. FEBS Lett, Netherlands: 587 (6), pp. 549-554. . (2013)
- 'Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker.'. Elsevier Eur J Cancer, Full text is available at: http://epubs.surrey.ac.uk/769595/
Despite significant advances in our understanding of the molecular pathology of bladder cancer, it remains a significant health problem with high morbidity and mortality associated with muscle-invasive bladder cancer (stages T2+), and high costs associated with the surveillance of non-muscle-invasive bladder cancer (NMIBC, stages Ta/T1/Tis). Moreover, current diagnostic biomarkers are suboptimal and of poor utility for low grade disease and surveillance. In this study, we show that the Engrailed-2 (EN2) transcription factor is expressed in, and secreted by, bladder cancer cell lines and patient tumour specimens, justifying an evaluation of urinary EN2 as a diagnostic biomarker in bladder cancer using archived samples from an established biospecimen collection. In patients with NMIBC, urinary EN2 was detected in most cases with an overall sensitivity of 82% and specificity of 75%. The sensitivity for stage Ta and T1 tumours was 71% and 76%, respectively, and 94% for stage T2+ tumours. This compares favourably with existing markers. The sensitivity for tumour grades 1, 2 and 3 was 69%, 78% and 87%, respectively. Thus urinary EN2 has the potential to be a more sensitive and specific protein biomarker for NMIBC than currently available tests.
- 'PBX3 is an important cofactor of HOXA9 in leukemogenesis'. Blood, 121 (8), pp. 1422-1431. . (2013)
- 'Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma'. Cancer Chemotherapy and Pharmacology, , pp. 1-8. . (2013)
- 'Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men.'. Sci Rep, England: 3doi: 10.1038/srep02059
- 'The role of HOX genes in normal hematopoiesis and acute leukemia.'. Nature Publishing Group Leukemia, doi: 10.1038/leu.2012.356Full text is available at: http://epubs.surrey.ac.uk/744438/
The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overexpressed in their wild type form. This review covers our current understanding of the role of HOX genes in normal hematopoiesis, AML and ALL, with particular emphasis on the similarities and differences of HOX function in these contexts, their hematopoietic downstream genes targets and implications for therapy.Leukemia accepted article preview online, 5 December 2012; doi:10.1038/leu.2012.356.
- 'Targeting the HOX/PBX dimer in breast cancer.'. Springer Breast Cancer Res Treat, Netherlands: 136 (2), pp. 389-398. . (2012)
- 'Targeting the HOX/PBX dimer in breast cancer'. Breast Cancer Research and Treatment, 136 (2), pp. 389-398. . (2012)
- 'Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer'. BJU International, 110 (6B) . (2012)
- 'Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer.'. Wiley-Blackwell BJU Int, England: 110 (6 Pt B), pp. E287-E292. . (2012)
- 'Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway.'. BMC Cancer, England: 12 . (2012)
- 'Antiangiogenic effects of zoledronate on cancer neovasculature.'. Future Oncol, England: 7 (11), pp. 1325-1333.doi: 10.2217/fon.11.113
- 'Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer.'. Clin Cancer Res, United States: 17 (5), pp. 1090-1098.Full text is available at: http://epubs.surrey.ac.uk/2751/
Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men.
- 'ENGRAILED-2 (EN2): A HIGHLY SPECIFIC URINARY BIOMARKER FOR THE EARLY DIAGNOSIS OF PROSTATE CANCER'. ELSEVIER SCIENCE BV EUR UROL SUPPL, 10 (2), pp. 64-64. . (2011)
- 'HOX genes in pancreatic development and cancer.'. JOP, Italy: 12 (3), pp. 216-219. . (2011)
- 'Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer.'. Biomed Central BMC Cancer, England: 11Full text is available at: http://epubs.surrey.ac.uk/107390/
Reovirus type 3 Dearing (T3D) has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication.
- 'HOX genes in ovarian cancer'. Springer Journal of Ovarian Research, 4 (1)Full text is available at: http://epubs.surrey.ac.uk/711372/
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.
- 'Immunoregulatory effects of freeze injured whole tumour cells on human dendritic cells using an in vitro cryotherapy model'. ACADEMIC PRESS INC ELSEVIER SCIENCE CRYOBIOLOGY, 61 (3), pp. 268-274. . (2010)
- 'Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells'. NATURE PUBLISHING GROUP LEUKEMIA, 24 (9), pp. 1555-1565.doi: 10.1038/leu.2010.142
- 'Differential effects of Paclitaxel on dendritic cell function'. BIOMED CENTRAL LTD BMC IMMUNOLOGY, 11 Article number ARTN 14 . (2010)
- 'Targeting HOX and PBX transcription factors in ovarian cancer'. BIOMED CENTRAL LTD BMC CANCER, 10 Article number ARTN 89 Full text is available at: http://epubs.surrey.ac.uk/227161/
- 'Enhancing prostate cancer cryotherapy using tumour necrosis factor related apoptosis-inducing ligand (TRAIL) sensitisation in an in vitro cryotherapy model'. ACADEMIC PRESS INC ELSEVIER SCIENCE CRYOBIOLOGY, 59 (2), pp. 207-213. . (2009)
- 'Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma'. AMER ASSOC CANCER RESEARCH CLINICAL CANCER RESEARCH, 15 (19), pp. 6158-6166.Full text is available at: http://epubs.surrey.ac.uk/227160/
- 'Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy (vol 100, pg 1889, 2009)'. NATURE PUBLISHING GROUP BRITISH JOURNAL OF CANCER, 101 (3), pp. 549-549. . (2009)
- 'Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy'. NATURE PUBLISHING GROUP BRITISH JOURNAL OF CANCER, 100 (12), pp. 1889-1895. . (2009)
- 'HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer)'. NATURE PUBLISHING GROUP BRITISH JOURNAL OF CANCER, 100 (3), pp. 470-475. . (2009)
- 'Disrupting the Interaction Between HOX and PBX Causes Necrotic and Apoptotic Cell Death in the Renal Cancer Lines CaKi-2 and 769-P'. ELSEVIER SCIENCE INC J UROLOGY, 180 (5), pp. 2196-2201. . (2008)
- 'Differential expression of HOX genes upon activation of leukocyte sub-populations'. SPRINGER TOKYO INTERNATIONAL JOURNAL OF HEMATOLOGY, 87 (3), pp. 246-249.Full text is available at: http://epubs.surrey.ac.uk/2593/
- 'Disrupting the interaction between Hox and PBX causes apoptotic cell death and reduces in vivo proliferation of a non-small cell lung cancer model'. AMER ASSOC CANCER RESEARCH MOLECULAR CANCER THERAPEUTICS, 6 (12), pp. 3504S-3504S. . (2007)
- 'Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma'. AMER ASSOC CANCER RESEARCH CANCER RESEARCH, 67 (12), pp. 5806-5813. . (2007)
- 'Calcium insensitivity of FA-6, a cell line derived from a pancreatic cancer associated with humoral hypercalcemia, is mediated by the significantly reduced expression of the Calcium Sensitive Receptor transduction component p38 MAPK'. BIOMED CENTRAL LTD MOLECULAR CANCER, 5 Article number ARTN 51 Full text is available at: http://epubs.surrey.ac.uk/2595/
- 'Engrailed: Complexity and economy of a multi-functional transcription factor'. ELSEVIER SCIENCE BV FEBS LETTERS, 580 (11), pp. 2531-2533. . (2006)
- 'Hox genes: a continuation of embryonic patterning?'. ELSEVIER SCIENCE LONDON TRENDS IN GENETICS, 22 (2), pp. 67-69. . (2006)
- 'The role of miR-196a and HOXB9 in head and neck squamous cell carcinoma'. ELSEVIER SCI LTD EUROPEAN JOURNAL OF CANCER, Amsterdam, NETHERLANDS: 17th ECCO / 38th ESMO / 32nd ESTRO European Cancer Congress on Reinforcing Multidisciplinarity 49, pp. S121-S121. . (2013)
- 'Urinary Engrailed-2 (EN2) levels and their correlation with tumour volume and pathological tumour stage in men undergoing radical prostatectomy for prostate cancer'. WILEY-BLACKWELL BJU INTERNATIONAL, Manchester, ENGLAND: Annual Scientific Meeting of the British-Association-of-Urological-Surgeons (BAUS) 111, pp. 12-12. . (2013)
- 'The HOXA/PBX3 Pathway Is an Attractive Therapeutic Target in MLL-Rearranged Acute Leukemia'. AMER SOC HEMATOLOGY BLOOD, Atlanta, GA: 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) 120 (21) . (2012)
- 'Modulation of Regulatory T Cells by Targeting The NFAT-FOXP3 Protein: Protein Interaction'. LIPPINCOTT WILLIAMS & WILKINS JOURNAL OF IMMUNOTHERAPY, North Bethesda, MD: 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) 35 (9), pp. 775-775. . (2012)
- 'HOX GENE EXPRESSION IN OVARIAN CANCER'. OXFORD UNIV PRESS ANNALS OF ONCOLOGY, Vienna, AUSTRIA: 37th Congress of the European-Society-for-Medical-Oncology (ESMO) 23, pp. 68-68. . (2012)
- 'HXR9 AND PARP INHIBITION -A NOVEL THERAPEUTIC IN OVARIAN CANCER'. OXFORD UNIV PRESS ANNALS OF ONCOLOGY, Vienna, AUSTRIA: 37th Congress of the European-Society-for-Medical-Oncology (ESMO) 23, pp. 325-325. . (2012)
- 'The Role of MiRNA-196a and HOXB9 in Head and Neck Cancer'. ELSEVIER SCI LTD EUROPEAN JOURNAL OF CANCER, Barcelona, SPAIN: 22nd Biennial Congress of the European-Association-for-Cancer-Research 48, pp. S52-S52. . (2012)
- 'Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role for EN2?'. AMER SOC CLINICAL ONCOLOGY JOURNAL OF CLINICAL ONCOLOGY, Chicago, IL: 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) 30 (15) . (2012)
- 'Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer'. WILEY-BLACKWELL BRITISH JOURNAL OF SURGERY, Royal Coll Surgery, Dublin, IRELAND: Annual Meeting of the Society-of-Academic-and-Research-Surgery 98, pp. 47-48. . (2011)
- 'Inhibition of the aquaporin water channels (AQPs) increases the sensitivity of DU145 cells to cryotherapy'. WILEY-BLACKWELL PUBLISHING, INC BJU INTERNATIONAL, Glasgow, SCOTLAND: Annual Meeting of the British-Association-of-Urological-Surgeons 103, pp. 21-21. . (2009)
- 'Cellular effects of phosphoramide mustard, the active metabolite of cyclophosphamide, on naturally-occuring human CD4(+) CD25(+) regulatory T cells'. LIPPINCOTT WILLIAMS & WILKINS JOURNAL OF IMMUNOTHERAPY, Boston, MA: 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer 30 (8), pp. 887-887. . (2007)
BMS3007: Cancer: Pathogenesis and Therapeutics
BMS3038: Molecular Genetics of Cancer
MSc Clinical Pharmacology
Senior Lecturer in Cell and Developmental Biology
Postgraduate admissions tutor for the PGMS
Chair of the MD committee