Dr Richard Morgan

Senior Lecturer in Molecular Oncology

Qualifications: BSc PhD

Email:
Phone: Work: 01483 68 8618
Room no: 29 PGM 02

Office hours

9am to 5pm Mon-Fri

Further information

Biography

Education

BA Hons. in Natural Sciences - Chemistry, Biochemistry, Maths and Statistics (2i). University of Cambridge 1990.

 

Ph.D. in Biochemistry - University of Birmingham 1993.

 

Previous positions

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.

 

 

Research Interests

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.

 

A link to a recent press release about the new prostate cancer diagnostic, EN2

Publications

Journal articles

  • Morgan R, Boxall A, Simpson GR, Michael A, Pandha HS, Harrington KJ. (2014) 'Targeting HOX transcription factors in prostate cancer'. BMC Urology, 14 (1)

    Abstract

    Background: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. Methods. HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. Results: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. Conclusion: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer. © 2014 Morgan et al.; licensee BioMed Central Ltd.

  • Ando H, Natsume A, Ohno M, Iwami K, Ohka F, Motomura K, Kinjo S, Ito M, Wakabayashi T, Senga T, Watanabe R, Ito I, Saito K, Morgan R. (2014) 'Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma'. Cancer Chemotherapy and Pharmacology, 73 (1), pp. 53-60.

    Abstract

    Background: Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX. Methods: We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers. Results: We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors. Conclusion: There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease. © 2013 Springer-Verlag Berlin Heidelberg.

  • McGrath SE, Michael A, Morgan R, Pandha H. (2013) 'EN2: a novel prostate cancer biomarker.'. Biomark Med, England: 7 (6), pp. 893-901.

    Abstract

    Extensive efforts to identify a clinically useful biomarker for the diagnosis of prostate cancer have resulted in important insights into the biology of the disease, but no new test has been approved by regulatory authorities. The unmet need has also shifted to identifying biomarkers that not only diagnose prostate cancer but also indicate whether the patient has 'significant' disease. EN2 is a homeobox-containing transcription factor secreted specifically by prostate cancers into urine, where it can be detected by a simple ELISA assay. A number of studies have demonstrated the enormous potential of EN2 to address this unmet need and provide the urologist with a simple, cheap and efficient prostate cancer biomarker.

  • Errico MC, Felicetti F, Bottero L, Mattia G, Boe A, Felli N, Petrini M, Bellenghi M, Carè A, Pandha HS, Morgan R, Calvaruso M, Tripodo C, Colombo MP. (2013) '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.

    Abstract

    Cutaneous melanoma is the fastest increasing cancer worldwide. Although several molecular abnormalities have been associated with melanoma progression, the underlying mechanisms are still largely unknown and few targeted therapies are under evaluation. Here we show that the HOXB7/PBX2 dimer acts as a positive transcriptional regulator of the oncogenic microRNA-221 and -222. In addition, demonstrating c-FOS as a direct target of miR-221&222, we identify a HOXB7/PBX2→miR-221&222 →c-FOS regulatory link, whereby the abrogation of functional HOXB7/PBX2 dimers leads to reduced miR-221&222 transcription and elevated c-FOS expression with consequent cell death. Taking advantage of the treatment with the peptide HXR9, an antagonist of HOX/PBX dimerization, we recognize miR-221&222 as effectors of its action, in turn confirming the HXR9 efficacy in the treatment of human melanoma malignancy, whilst sparing normal human melanocytes. Our findings, besides suggesting the potential therapeutic of HXR9 or its derivatives in malignant melanoma, suggest the disruption of the HOXB7/PBX2 complexes, miR-221&222 inhibition or even better their combination, as innovative therapeutic approaches. What's new? Cutaneous melanoma is the fastest increasing cancer worldwide. Although several molecular abnormalities have been associated with melanoma progression, the underlying mechanisms are still largely unknown. Here the authors show that the HOXB7/PBX2 complex is a new transcriptional activator of the oncogenic microRNA-221 and 222 in melanoma inducing tumor malignancy. The authors also identified c-FOS as a direct target of miR-221&222 whose repression causes reduced apoptosis. The abrogation of HOXB7 and/or miR-221&222 or the disruption of HOXB7/PBX2 dimers by the peptide HXR9 might thus represent novel molecular approaches for advanced melanoma, an aggressive neoplasm refractory to traditional therapies. Copyright © 2013 UICC.

  • Morgan R, Javed S, Launchbury F, Pandha H, Bryan RT, James ND, Wallace DMA, Ward DG, Zeegers MP, Cheng KK, Hurst CD, Knowles MA. (2013) '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.

    Abstract

    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.© 2013 Elsevier Ltd. All rights reserved.

  • Alharbi RA, Pandha HS, Morgan R, Pettengell R. (2013) 'The role of HOX genes in normal hematopoiesis and acute leukemia'. Leukemia, 27 (5), pp. 1000-1008.

    Abstract

    The homeobox (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 gene targets and implications for therapy. © 2013 Macmillan Publishers Limited All rights reserved.

  • McGrath SE, Michael A, Pandha H, Morgan R. (2013) 'Engrailed homeobox transcription factors as potential markers and targets in cancer.'. FEBS Lett, Netherlands: 587 (6), pp. 549-554.

    Abstract

    Engrailed (En) is a member of the homeobox gene family, which encodes a homeodomain-containing transcription factor that is essential during early development. The only known site of normal adult Engrailed protein (EN) expression is in the nervous system, and it has been implicated in the development of both young-onset Parkinson's disease as well as autism. Over-expression of EN has been linked to tumour development in adults, particularly in breast, prostate, melanoma and ovarian cancers, and there is a growing interest in its role as a diagnostic and prognostic biomarker. It is hoped that further work may confirm associations between En expression and therapy-resistant, poor prognosis cancers, similar to that identified with other homeobox gene profiles.

  • McGrath SE, Michael A, Pandha H, Morgan R. (2013) 'Engrailed homeobox transcription factors as potential markers and targets in cancer'. FEBS Letters, 587 (6), pp. 549-554.

    Abstract

    Engrailed (En) is a member of the homeobox gene family, which encodes a homeodomain-containing transcription factor that is essential during early development. The only known site of normal adult Engrailed protein (EN) expression is in the nervous system, and it has been implicated in the development of both young-onset Parkinson's disease as well as autism. Over-expression of EN has been linked to tumour development in adults, particularly in breast, prostate, melanoma and ovarian cancers, and there is a growing interest in its role as a diagnostic and prognostic biomarker. It is hoped that further work may confirm associations between En expression and therapy-resistant, poor prognosis cancers, similar to that identified with other homeobox gene profiles. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  • Morgan R, Bryan RT, Javed S, Launchbury F, Zeegers MP, Cheng KK, James ND, Wallace DM, Hurst CD, Ward DG, Knowles MA, Pandha H. (2013) 'Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker.'. Eur J Cancer,

    Abstract

    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.

  • Li Z, Li Y, Arnovitz S, Chen P, Huang H, Jiang X, Hong G-M, Kunjamma RB, Ren H, He C, Neilly MB, Rowley JD, Chen J, Zhang Z, Wang C-Z, Yuan C-S, Elkahloun AG, Liu PP, Valk PJM, Delwel R, Löwenberg B, Döhner K, Bullinger L, Morgan R. (2013) 'PBX3 is an important cofactor of HOXA9 in leukemogenesis'. Blood, 121 (8), pp. 1422-1431.

    Abstract

    Although PBX proteins are known to increase DNA-binding/transcriptional activity of HOX proteins through their direct binding, the functional importance of their interaction in leukemogenesis is unclear. We recently reported that overexpression of a 4-homeobox-gene signature (ie, PBX3/HOXA7/HOXA9/HOXA11) is an independent predictor of poor survival in patients with cytogenetically abnormal acute myeloid leukemia (CA-AML). Here we show that it is PBX3, but not PBX1 or PBX2, that is consistently coexpressed with HOXA9 in various subtypes of CA-AML, particularly MLL-rearranged AML, and thus appears as a potential pathologic cofactor of HOXA9 in CA-AML. We then show that depletion of endogenous Pbx3 expression by shRNA significantly inhibits MLL-fusion-mediated cell transformation, and coexpressed PBX3 exhibits a significantly synergistic effect with HOXA9 in promoting cell transformation in vitro and leukemogenesis in vivo. Furthermore, as a proof of concept, we show that a small peptide, namely HXR9, which was developed to specifically disrupt the interactions between HOX and PBX proteins, can selectively kill leukemic cells with overexpression of HOXA/PBX3 genes. Collectively, our data suggest that PBX3 is a critical cofactor of HOXA9 in leukemogenesis, and targeting their interaction is a feasible strategy to treat presently therapy resistant CA-AML (eg, MLL-rearranged leukemia) in which HOXA/PBX3 genes are overexpressed.

  • Ando H, Natsume A, Ohno M, Iwami K, Ohka F, Motomura K, Kinjo S, Ito M, Wakabayashi T, Senga T, Watanabe R, Ito I, Saito K, Morgan R. (2013) 'Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma'. Cancer Chemotherapy and Pharmacology, , pp. 1-8.

    Abstract

    Background: Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX. Methods: We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers. Results: We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors. Conclusion: There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease. © 2013 Springer-Verlag Berlin Heidelberg.

  • Killick E, Morgan R, Launchbury F, Bancroft E, Page E, Castro E, Kote-Jarai Z, Aprikian A, Blanco I, Clowes V, Domchek S, Douglas F, Eccles D, Evans DG, Harris M, Kirk J, Lam J, Lindeman G, Mitchell G, Pachter N, Selkirk C, Tucker K, Zgajnar J, Eeles R, Pandha H. (2013) 'Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men.'. Sci Rep, England: 3

    Abstract

    Controversy surrounds the use of PSA as a biomarker for prostate cancer detection, leaving an unmet need for a novel biomarker in this setting; urinary EN2 may identify individuals with clinically relevant prostate cancer. Male BRCA1 and BRCA2 mutation carriers are at increased risk of clinically significant prostate cancer and may benefit from screening. Urine samples from 413 BRCA1 and BRCA2 mutation carriers and controls were evaluated. Subjects underwent annual PSA screening with diagnostic biopsy triggered by PSA > 3.0 ng/ml; 21 men were diagnosed with prostate cancer. Urinary EN2 levels were measured by ELISA and had a sensitivity of 66.7% and specificity of 89.3% for cancer detection. There was no statistically significant difference in EN2 levels according to genetic status or Gleason score. Urinary EN2 may be useful as a non-invasive early biomarker for prostate cancer detection in genetically high-risk individuals.

  • Alharbi RA, Pettengell R, Pandha HS, Morgan R. (2012) 'The role of HOX genes in normal hematopoiesis and acute leukemia.'. Leukemia,

    Abstract

    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.

  • Morgan R, Boxall A, Harrington KJ, Simpson GR, Gillett C, Michael A, Pandha HS. (2012) 'Targeting the HOX/PBX dimer in breast cancer.'. Breast Cancer Res Treat, Netherlands: 136 (2), pp. 389-398.

    Abstract

    The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in a number of malignancies, including breast cancer. While relatively little is known about the roles that individual HOX genes play in cancer, it is however clear that these roles can be both contradictory, with some members acting as oncogenes and some as tumor suppressors, and also redundant, with several genes essentially having the same function. Here, we have attempted to address this complexity using the HXR9 peptide to target the interaction between HOX proteins and PBX, a second transcription factor that serves as a common co-factor for many HOX proteins. We show that HXR9 causes apoptosis in a number of breast cancer-derived cell lines and that sensitivity to HXR9 is directly related to the averaged expression of HOX genes HOXB1 through to HOXB9, providing a potential biomarker to predict the sensitivity of breast tumors to HXR9 or its derivatives. Measuring the expression of HOX genes HOXB1-HOXB9 in primary tumors revealed that a subset of tumors show highly elevated expression indicating that these might be potentially very sensitive to killing by HXR9. Furthermore, we show that while HXR9 blocks the oncogenic activity of HOX genes, it does not affect the known tumor-suppressor properties of a subset of HOX genes in breast cancer.

  • Morgan R, Boxall A, Simpson GR, Michael A, Pandha HS, Harrington KJ, Gillett C. (2012) 'Targeting the HOX/PBX dimer in breast cancer'. Breast Cancer Research and Treatment, 136 (2), pp. 389-398.

    Abstract

    The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in a number of malignancies, including breast cancer. While relatively little is known about the roles that individual HOX genes play in cancer, it is however clear that these roles can be both contradictory, with some members acting as oncogenes and some as tumor suppressors, and also redundant, with several genes essentially having the same function. Here, we have attempted to address this complexity using the HXR9 peptide to target the interaction between HOX proteins and PBX, a second transcription factor that serves as a common co-factor for many HOX proteins. We show that HXR9 causes apoptosis in a number of breast cancer-derived cell lines and that sensitivity to HXR9 is directly related to the averaged expression of HOX genes HOXB1 through to HOXB9, providing a potential biomarker to predict the sensitivity of breast tumors to HXR9 or its derivatives. Measuring the expression of HOX genes HOXB1-HOXB9 in primary tumors revealed that a subset of tumors show highly elevated expression indicating that these might be potentially very sensitive to killing by HXR9. Furthermore, we show that while HXR9 blocks the oncogenic activity of HOX genes, it does not affect the known tumor-suppressor properties of a subset of HOX genes in breast cancer. © Springer Science+Business Media New York 2012.

  • Pandha H, Morgan R, Sorensen KD, Orntoft TF, Borre M, Hoyer S, Langley S. (2012) 'Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer'. BJU International, 110 (6B)

    Abstract

    OBJECTIVES To evaluate the relationship between levels of a recently described prostate cancer biomarker engrailed-2 (EN2) in urine and cancer volume in men who had undergone radical prostatectomy (RP) for prostate cancer. To date, prostate-specific antigen (PSA) levels have not reliably predicted prostate cancer volume. Reliable volume indicator biomarker(s) may aid management decisions, e.g. active treatment vs active surveillance. Patients and Methods Archived patient samples from the Aarhus Prostate Cancer Project, Denmark, were assessed. Pre-treatment mid-stream urines, without preceding prostatic massage, were collected and stored at -80 °C. Urinary EN2 levels were measured by a recently published enzyme-linked immunosorbent assay. Results In all, 88 of the whole cohort of 125 men (70%) were positive for EN2 in their urine (>42.5 Âμg/L); 38/58 (65%) men where cancer volume data was available. There was no statistical relationship between urinary EN2 levels and serum PSA levels. PSA levels did not correlate with tumour stage, combined Gleason grade, total prostatic weight or cancer volume. There was a strong statistical relationship between urinary EN2 and prostate cancer volume by linear regression (P= 0.006). Higher EN2 levels correlated with tumour stage T1 vs T2 (P= 0.027). Conclusions Pre-surgical urinary EN2 levels were associated with increasing tumour stage and closely reflected the volume of cancer in RP specimens. Given the ease of collection (no prostatic massage required) and the simplicity, low cost and robustness of the assay, EN2 may become a useful biomarker in not only identifying which patients have prostate cancer but may also facilitate risk stratification by indicating the burden of tumour volume. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

  • Pandha H, Sorensen KD, Orntoft TF, Langley S, Hoyer S, Borre M, Morgan R. (2012) 'Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer.'. BJU Int, England: 110 (6 Pt B), pp. E287-E292.

    Abstract

    What's known on the subject? and What does the study add? There are a lot of potential prostate cancer biomarkers being evaluated. All aim to improve on the sensitivity and specificity of PSA. EN2 was recently shown by our group to have better sensitivity and specificity than PSA. EN2 is a simple ELISA test and is not dependent on other parameters, even PSA, unlike all the other current biomarkers under evaluation. To date, no marker correlates with the amount of cancer present - the present study shows this positive correlation with EN2 in men undergoing prostatectomy. The potential utility of this work is that by knowing that the level of EN2 corresponds to the amount of cancer present, irrelevant of tumour grade and number of cancer foci, we can define an EN2 level corresponding to small cancers, which can then undergo surveillance. We are conducting a further study that is aimed at determining whether the levels of EN2 in urine can indicate 'significant' vs 'non-significant cancer' using the threshold of 0.5 mL cancer (after Epstein's work).

  • Twigger K, Roulstone V, Kyula J, Karapanagiotou EM, Syrigos KN, Morgan R, White C, Bhide S, Nuovo G, Coffey M, Thompson B, Jebar A, Errington F, Melcher AA, Vile RG, Pandha HS, Harrington KJ. (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

    Abstract

    Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN.

  • Metcalf S, Pandha HS, Morgan R. (2011) 'Antiangiogenic effects of zoledronate on cancer neovasculature.'. Future Oncol, England: 7 (11), pp. 1325-1333.

    Abstract

    Angiogenesis, one of the hallmarks of cancer, supplies nutrients to cancerous tissues to facilitate rapid growth. Targeting cancer-associated angiogenesis is an important goal in cancer therapy and there are currently many drugs that affect tumor-associated vasculature. In this article, we will focus on the antiangiogenic effects of zoledronate (ZA), a bisphosphonate drug routinely used in the treatment of cancer-associated bone disease. This article covers the known effects of ZA throughout the clinical process. It also covers the animal models of cancer that have been treated with ZA and evaluated for angiogenes is, concluding with the current clinical data pertaining to angiogenic factors after ZA treatment.

  • Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, Whitaker HC, Neal DE, Ismail M, Whitaker H, Annels N, Michael A, Pandha H. (2011) '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.

    Abstract

    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.

  • Morgan RM, Ismail M, Boxall A, Bhaat A, Hindley R, Michael A, Langley SM, Zylstra J, Pandha HS. (2011) 'ENGRAILED-2 (EN2): A HIGHLY SPECIFIC URINARY BIOMARKER FOR THE EARLY DIAGNOSIS OF PROSTATE CANCER'. EUR UROL SUPPL, 10 (2), pp. 64-64.
  • Kelly ZL, Michael A, Butler-Manuel S, Pandha HS, Morgan RG. (2011) 'HOX genes in ovarian cancer'. Journal of Ovarian Research, 4 (1)

    Abstract

    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.

  • Gray S, Pandha HS, Michael A, Middleton G, Morgan R. (2011) 'HOX genes in pancreatic development and cancer.'. JOP, Italy: 12 (3), pp. 216-219.

    Abstract

    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.

  • Heinemann L, Simpson GR, Boxall A, Kottke T, Relph KL, Vile R, Melcher A, Prestwich R, Harrington KJ, Morgan R, Pandha HS. (2011) 'Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer.'. BMC Cancer, England: 11

    Abstract

    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.

  • Ismail M, Morgan R, Harrington K, Davies J, Pandha H. (2010) 'Immunoregulatory effects of freeze injured whole tumour cells on human dendritic cells using an in vitro cryotherapy model'. CRYOBIOLOGY, 61 (3), pp. 268-274.
  • Daniels TR, Neacato II, Rodriguez JA, Pandha HS, Morgan R, Penichet ML. (2010) 'Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells'. LEUKEMIA, 24 (9), pp. 1555-1565.
  • John J, Ismail M, Riley C, Askham J, Morgan R, Melcher A, Pandha H. (2010) 'Differential effects of Paclitaxel on dendritic cell function'. BMC IMMUNOLOGY, 11 Article number ARTN 14
  • Morgan R, Plowright L, Harrington KJ, Michael A, Pandha HS. (2010) 'Targeting HOX and PBX transcription factors in ovarian cancer'. BMC CANCER, 10 Article number ARTN 89
  • Ismail M, Morgan R, Harrington K, Davies J, Pandha H. (2009) 'Enhancing prostate cancer cryotherapy using tumour necrosis factor related apoptosis-inducing ligand (TRAIL) sensitisation in an in vitro cryotherapy model'. CRYOBIOLOGY, 59 (2), pp. 207-213.
  • Pandha HS, Heinemann L, Simpson GR, Melcher A, Prestwich R, Errington F, Coffey M, Harrington KJ, Morgan R. (2009) 'Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma'. CLINICAL CANCER RESEARCH, 15 (19), pp. 6158-6166.
  • Ismail M, Bokaee S, Morgan R, Davies J, Harrington KJ, Pandha H. (2009) 'Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy (vol 100, pg 1889, 2009)'. BRITISH JOURNAL OF CANCER, 101 (3), pp. 549-549.
  • Ismail M, Bokaee S, Davies J, Harrington KJ, Pandha H. (2009) 'Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy'. BRITISH JOURNAL OF CANCER, 100 (12), pp. 1889-1895.
  • Plowright L, Harrington KJ, Pandha HS, Morgan R. (2009) 'HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer)'. BRITISH JOURNAL OF CANCER, 100 (3), pp. 470-475.
  • Shears L, Plowright L, Harrington K, Pandha HS, Morgan R. (2008) 'Disrupting the Interaction Between HOX and PBX Causes Necrotic and Apoptotic Cell Death in the Renal Cancer Lines CaKi-2 and 769-P'. J UROLOGY, 180 (5), pp. 2196-2201.
  • Morgan R, Whiting K. (2008) 'Differential expression of HOX genes upon activation of leukocyte sub-populations'. INTERNATIONAL JOURNAL OF HEMATOLOGY, 87 (3), pp. 246-249.
  • Plowright L, Shears L, Pandha H, Morgan R. (2007) 'Disrupting the interaction between Hox and PBX causes apoptotic cell death and reduces in vivo proliferation of a non-small cell lung cancer model'. MOLECULAR CANCER THERAPEUTICS, 6 (12), pp. 3504S-3504S.
  • Morgan R, Pirard PM, Shears L, Sohal J, Pettengell R, Pandha HS. (2007) 'Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma'. CANCER RESEARCH, 67 (12), pp. 5806-5813.
  • Morgan R, Fairfax B, Pandha HS. (2006) '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'. MOLECULAR CANCER, 5 Article number ARTN 51
  • Morgan R. (2006) 'Engrailed: Complexity and economy of a multi-functional transcription factor'. FEBS LETTERS, 580 (11), pp. 2531-2533.
  • Morgan R. (2006) 'Hox genes: a continuation of embryonic patterning?'. TRENDS IN GENETICS, 22 (2), pp. 67-69.

Conference papers

  • Javed S, Morgan R, Hindley R, Bott S, Eden C, Pandha H, Langley S. (2014) 'Urinary engrailed-2 levels in healthy volunteers, patients on active surveillance and following radical prostate cancer treatment'. WILEY-BLACKWELL BJU INTERNATIONAL, Liverpool, ENGLAND: Annual Scientific Meeting of the British-Association-of-Urological-Surgeons (BAUS) 113, pp. 43-44.
  • Darda L, Lambert D, Morgan R, Murdoch C, Hunter K. (2013) '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.
  • Javed S, Pandha H, Morgan R, Bott S, Eden C, Langley S. (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.
  • Gray S, Metcalf S, Boxall A, Middleton G, Bagwan I, Pandha H, Morgan R. (2013) 'The chorio-allantoicmembrane (CAM) model for testing HOX gene antagonism in pancreatic cancer'. AMER ASSOC CANCER RESEARCH CANCER RESEARCH, Washington, DC: 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) 73 (8)
  • Li Z, Zhang Z, Li Y, Arnovitz S, Chen P, Huang H, Jiang X, Hong G-M, He C, Wang C-Z, Elkahloun A, Valk PJM, Dohner K, Neilly MB, Bullinger L, Delwel R, Lowenberg B, Liu PP, Morgan R, Rowley JD, Yuan C-S, Chen J. (2012) '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)
  • Annels NE, Simpson GR, Bokaee S, Riley C, Denyer M, Pandha H, Morgan R. (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.
  • Kelly Z, Pandha H, Madhuri K, Morgan R, Michael A. (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.
  • Kelly Z, Pandha H, Morgan R, Michael A. (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.
  • Darda L, Lambert D, Morgan R, Hunter K. (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.
  • Killick E, Morgan R, Launchbury F, Annels NE, Bancroft E, Page E, Castro E, Kote-Jarai Z, Eeles RA, Pandha HS. (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)
  • Pandha S, Heinemann L, Simpson GR, Boxall A, Relph K, Morgan R. (2011) '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.
  • Michael A, Plowright L, Boxall A, Bhatt A, Di Palma S, Parker C, Pandha H. (2010) 'Evaluation of EN2 as a urine-based biomarker for prostate cancer.'. J Clin Oncol 28, 2010 (suppl; abstr e15129), Chicago USA: ASCO

    Abstract

    Background: Prostate cancer is a leading cause of cancer related death in men but its diagnosis is still complicated by the lack of a highly predictive biochemical marker. Here we show that the transcription factor Engrailed-2 is secreted from prostate tumours in a highly specific manner and is present in the urine of men with prostate cancer. Methods: Urine was collected under standardised conditions from men with prostate cancer, or with non-cancerous conditions of the prostate such as benign prostatic hypertrophy, or men who were found to have no prostate abnormalities after saturation biopsy. Results: Engrailed-2 protein was detected in the untreated, unconcentrated urine of 62% of men with prostate cancer, but only 3% of men with no prostatic abnormalities (n=258, p<0.001). Conclusions: Thus Engrailed-2 is a potential diagnostic marker for prostate cancer.

  • Ismail M, Morgan R, Davies J, Pandha H. (2009) '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.
  • Meyer B, Denyer M, Morgan R, Pandha H. (2007) '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.

Teaching

Undergraduate

 

BMS3007: Cancer: Pathogenesis and Therapeutics

 

BMS3038: Molecular Genetics of Cancer

 

Postgraduate

 

MSc Clinical Pharmacology

Departmental Duties

Senior Lecturer in Cell and Developmental Biology

 

Postgraduate admissions tutor for the PGMS

 

Chair of the MD committee

Page Owner: eih442
Page Created: Tuesday 3 January 2012 15:21:05 by pr0004
Last Modified: Wednesday 10 October 2012 13:12:03 by eih437
Expiry Date: Saturday 27 November 2010 15:58:24
Assembly date: Tue Oct 21 23:06:51 BST 2014
Content ID: 70709
Revision: 3
Community: 1196