Neil Cross is a Senior lecturer in Molecular and Cellular Biology at Sheffield Hallam University.
Molecular and cellular biology
Neil's research interests are
1) Models of prostate cancer growth and survival
Factors regulating the activity of the anti-tumour agent TRAIL
Recent studies have focused on how tumours evade apoptotic signals from Tumour Necrosis Factor (TNF) superfamily members, with particular emphasis on the potential anti-tumour agent TRAIL (TNF-Related Apoptosis Inducing Ligand), its receptors (Death Receptors 4 and 5) and decoy receptors ( Decoy receptors 1 and 2) and OPG (Osteoprotegerin). Current studies are focusing on mechanisms of TRAIL resistance in cancer cells, and whether combinations of agents such as histone deactylase (HDAC) inhibitors, nuclear export inhibitors and proteasome inhibitors can reverse TRAIL resistance. In our recent studies, we have also demonstrated that nuclear export inhibitors in particular can potently enhance tumour cell sensitivity to TRAIL in a range of tumour cells. Role of cancer stem cells in tumour development
Recent evidence suggests that tumour comprise of differentiated tumour cells, which have a limited life-span, and cancer stem cells/tumour initiating cells, which are undifferentiated cells with unlimited replicative ability and the ability to differentiate. The cancer stem cells hypothesis suggests that if cancer stem cells are selectively ablated, tumour growth will ceases and eventually the tumour will regress. In this study, we are investigating whether cancer stem cells are present in primary uveal melamona tissue, and if present, whether they can be selectively targeted by chemotherapeutic agents. This study is based on our observations that 'primitive' tumourigenic sub-populations of cells with no cytogenetic aberrations are present in uveal melanoma tumours, in contrast to the majority of the cells within the tumour. These cytogenetically 'normal' tumour cells may represent cells at the earliest stage in tumour development and hence, may represent the cancer stem cell population in uveal melanoma. Related studies on prostate cancer are also addressing the cancer stem cell hypothesis.
The role of Nanog in prostate cancer stem cells
These studies are investigating the role of the embryonic stem cell marker Nanog in the development of the cancer stem cell phenotype. Cancer stem cells are thought to be the 'root' of cancer, and selectively targeting these cells may have therapeutic implications. Using Nanog-reporter cell lines, we are isolating and characterising Nanog-positive cells from bulk populations, and assessing their phenotype.
In vivo imaging of tumour growth in bone
To directly visualise tumour metastasis to bone in experimental in vivo models, and to assess tumour colonisation within bone, Green Fluorescence Protein (GFP)-based imaging of tumours has been developed in collaboration with Dr Colby Eaton, University of Sheffield. Using GFP-transfected PC3 prostate cancer cells and a Lightools illumination system, tumours which are less than 1mm in diameter have been detected in the bone marrow cavity of live mice in our studies, allowing the study of early tumour-bone interactions. This technology has also been successfully applied to visualise tumour regression in response to treatment with anti-tumour agents, such as TRAIL, in live animals.
These studies are in collaboration with Dr Colby Eaton, Academic Unit of Urology, University of Sheffield.
2) Molecular detection of Chlamydia trachomatis and its role in infertility
Chlamydia trachomatis is one of the most prevalent sexually transmitted diseases, and is a major cause of infertility. Since it is an obligate intracellular pathogen, the culture and subsequent detection of viable Chlamydia is problematic. This is further complicated by persistent forms of the bacteria, (in response to antibiotics or endogenous interferon), which may be non-culturable but potentially viable. Earlier studies, in collaboration with Dr Adrian Eley (University of Sheffield) demonstrated to use of molecular detection of Chlamydial transcripts as an alternative to culture-based antimicrobial susceptibility testing. More recently, our studies, in collaboration with Dr Allan Pacey, Dr Adrian Eley and Professor Roy Jennings at The University of Sheffield, have used Real-Time PCR to quantify Chlamydia attachment to sperm in samples used for IVF, even after a washing procedure used to remove any bacteria present. Our ongoing studies are focused on developing methods for the study of 'persistent' forms of Chlamydia in vitro, and gene expression profiling for 'persistent' forms of Chlamydia.
Dr Tom Sayers, National Cancer Institute, National Institutes of Health, USA
Dr Colby Eaton, Academic Urology Unit, University of Sheffield
Dr Karen Sisley, Department of Ophthalmology and Orthoptics, University of Sheffield Medical School
Professor Roy Jennings/Dr Adrian Eley/Dr Allan Pacey, Academic Unit of Medical Microbiology/Reproductive Health, University of Sheffield
Yorkshire Cancer Research
Weston Park Hospital Cancer Appeal
Bone Cancer research Trust
International Centre for Studies and Research in Biomedicine (ICB)
Biomedical Research Centre, Sheffield Hallam University
DOHERTY, Rachel E., SISLEY, Karen, HAMMOND, David W., RENNIE, Ian G. and CROSS, Neil (2017). Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics. Investigative Opthalmology & Visual Science, 58 (12), p. 5387.
ARHOMA, A., CHANTRY, A. D., HAYWOOD-SMALL, Sarah and CROSS, Neil (2017). SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture. Experimental cell research.
MAHBUB, Amani, LE MAITRE, Christine, HAYWOOD-SMALL, Sarah, CROSS, Neil and JORDAN-MAHY, Nikki (2017). Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines. Oncotarget, 8 (37).
CHEN, Yu-Su, ALLEN, David, CROSS, Neil A, PITAK, Mateusz B, TIZZARD, Graham J, COLES, Simon J and BRICKLEBANK, Neil (2017). Biological and structural studies of phosphonium 'masked thiolate' compounds. European Journal of Medicinal Chemistry, 125, 528-537.
HARVEY, Amanda, DAY, Rebecca, COLE, Laura M., BARTLETT, Maggie, WARWICK, John, BOJAR, Richard, SMITH, David, CROSS, Neil and CLENCH, Malcolm R. (2016). MALDI-MSI for the analysis of a 3D tissue-engineered psoriatic skin model. Proteomics, 16 (11-12), 1718-1725.
MAHBUB, A.A., LE MAITRE, C.L., HAYWOOD-SMALL, S.L., CROSS, N.A. and JORDAN-MAHY, N. (2015). Glutathione is key to the synergistic enhancement of doxorubicin and etoposide by polyphenols in leukaemia cell lines. Cell Death and Disease, 6, e2028.
MAHBUB, A.A., LE MAITRE, C.L., HAYWOOD-SMALL, S.L., CROSS, N.A. and JORDAN-MAHY, N. (2015). Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. Cell Death Discovery, 1 (15043), 1-12.
ZAINI, R, HAYWOOD-SMALL, S, CROSS, Neil and LE MAITRE, Christine (2015). Differential interactions of Falcarinol combined with anti-tumour agents on cellular proliferation and apoptosis in human lymphoid leukaemia cell lines. Journal of Blood Disorders and Transfusion, 6 (2).
LALWANI, Nikhil, CHEN, Yu-Su, CROSS, Neil, BROOKE, Gemma, ALLEN, David W., REYNOLDS, Alan, OJEDA, Jesús, TIZZARD, Graham J., COLES, Simon J. and BRICKLEBANK, Neil (2015). Triphenylarsonium-functionalised gold nanoparticles : potential nanocarriers for intracellular therapeutics. Chemical Communications, 51 (19), 4109-4111.
MAHBUB, Amani A, LE MAITRE, Christine, HAYWOOD-SMALL, Sarah, MCDOUGALL, Gordon J, CROSS, Neil and JORDAN-MAHY, N. (2013). Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines. Anti-cancer agents in medicinal chemistry, 13 (10), 1601-1613.
SINGH MUDHAR, Hardeep S., SCOTT, Ian, UL-HASSAN, Aliya, BURTON, David, DOHERTY, Rachel, CROSS, Neil, RENNIE, Ian G. and SISLEY, Karen (2012). Bilateral diffuse uveal melanocytic hyperplasia (BDUMP)-molecular characterisation and novel association with bilateral renal papillary carcinoma. Histopathology, 61 (4), 751-754.
DOHERTY, R.E., HAYWOOD-SMALL, Sarah, SISLEY, K. and CROSS, Neil (2011). Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells. Biochemical and Biophysical Research Communications, 414 (4), 801-807.
MUTHANA, M., GIANNOUDIS, A., SCOTT, S. D., FANG, H.-Y., COFFELT, S. B., MORROW, F. J., MURDOCH, C., BURTON, J. L., CROSS, N., BURKE, B., MISTRY, R., HAMDY, F., BROWN, N. J., GEORGOPOULOS, L., HOSKIN, P. J., ESSAND, M., LEWIS, C. E. and MAITLAND, N. J. (2011). Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors. Cancer Research, 71, 1805-1815.
SISLEY, K, DOHERTY, R and CROSS, Neil (2011). What hope for the future? GNAQ and uveal melanoma. British Journal of Ophthalmology, 95 (5), 620-623.
KOKAB, A., JENNINGS, R., ELEY, A., PACEY, A. A. and CROSS, N. A. (2010). Analysis of modulated gene expression in a model of Interferon-gamma-induced persistence of Chlamydia trachomatis in HEp-2 cells. Microbial Pathogenesis, 49 (5), 217-225.
AL-MOUSLY, N., CROSS, N. A., ELEY, A. and PACEY, A. A. (2009). Real-time polymerase chain reaction shows that density centrifugation does not always remove Chlamydia trachomatis from human semen. Fertility and sterility, 92 (5), 1606-1615.
GUZMÁN-RAMÍREZ, N., VÖLLER, M., WETTERWALD, A., GERMANN, M., CROSS, N. A., RENTSCH, C. A., SCHALKEN, J., THALMANN, G. N. and CECCHINI, M. G. (2009). In vitro propagation and characterization of neoplastic stem/progenitor-like cells from human prostate cancer tissue. The Prostate, 69 (15), 1683-1693.
TOZER, G. M., AKERMAN, S., CROSS, N. A., BARBER, P. R., BJORNDAHL, M. A., GRECO, O., HARRIS, S., HILL, S. A., HONESS, D. J., IRESON, C. R., PETTYJOHN, K. L., PRISE, V. E., ALDASORO, C. C. R., RUHRBERG, C., SHIMA, D. T. and KANTHOU, C. (2008). Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors. Cancer research, 68 (7), 2301-2311.
CROSS, N. A., FOWLES, A., REEVES, K., JOKONYA, N., LINTON, K., HOLEN, I., HAMDY, F. C. and EATON, C. L. (2008). Imaging the effects of castration on bone turnover and hormone-independent prostate cancer colonization of bone. The Prostate, 68 (15), 1707-1714.
CROSS, N., WATERMAN, E. A., JOKONYA, N., FOWLES, A., BUCKLE, C. H., PHILLIPS, J., HOLEN, I., HAMDY, F. C. and EATON, C. L. (2008). Phenotypic variations of TRAIL sensitivity in cloned populations of prostate cancer cells. Journal of cellular biochemistry, 104 (4), 1452-1464.
CROSS, N A, PAPAGEORGIOU, M and EATON, C L (2007). Bone marrow stromal cells promote growth and survival of prostate cancer cells. Biochemical Society Transactions, 35 (Pt 4), 698-700.
BRYANT, R J, CROSS, N A, EATON, C L, HAMDY, F C and CUNLIFFE, V T (2007). EZH2 promotes proliferation and invasiveness of prostate cancer cells. The Prostate, 67 (5), 547-556.
CROSS, Neil A, REID, Sheilagh V, HARVEY, Amanda J, JOKONYA, Nickie and EATON, Colby L (2006). Opposing actions of TGFbeta1 and FGF2 on growth, differentiation and extracellular matrix accumulation in prostatic stromal cells. Growth Factors, 24 (4), 233-241.
CROSS, N A, GANESH, A, PARPIA, M, MURRAY, A K, RENNIE, I G and SISLEY, K (2006). Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma. Eye, 20 (4), 476-81.
HOLEN, Ingunn, CROSS, Simon S, NEVILLE-WEBBE, Helen L, CROSS, Neil A, BALASUBRAMANIAN, Sabapathy P, CROUCHER, Peter I, EVANS, C Alyson, LIPPITT, Jennifer M, COLEMAN, Robert E and EATON, Colby L (2005). Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo - a role in tumour cell survival? Breast Cancer Research and Treatment, 92 (3), 207-15.
CROSS, N A, CHANDRASEKHARAN, S, JOKONYA, N, FOWLES, A, HAMDY, F C, BUTTLE, D J and EATON, C L (2005). The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican. The Prostate, 63 (3), 269-75.
CROSS, Neil A, RENNIE, Ian G, MURRAY, Anna K and SISLEY, Karen (2005). The identification of chromosome abnormalities associated with the invasive phenotype of uveal melanoma in vitro. Clinical & Experimental Metastasis, 22 (2), 107-113.
NYAMBO, Rachel, CROSS, Neil, LIPPITT, Jenny, HOLEN, Ingunn, BRYDEN, Gorden, HAMDY, Freddie C and EATON, Colby L (2004). Human bone marrow stromal cells protect prostate cancer cells from TRAIL-induced apoptosis. Journal of Bone and Mineral Research (JBMR), 19 (10), 1712-1721.
NEVILLE-WEBBE, H L, CROSS, N A, EATON, C L, NYAMBO, R, EVANS, C A, COLEMAN, R E and HOLEN, I (2004). Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis. Breast Cancer Research and Treatment, 86 (3), 269-279.
DIZEYI, N, BJARTELL, A, NILSSON, E, HANSSON, J, GADALEANU, V, CROSS, Neil and ABRAHAMSSON, P-A (2004). Expression of serotonin receptors and role of serotonin in human prostate cancer tissue and cell lines. The Prostate, 59 (3), 328-336.
CROSS, Neil A, MURRAY, Anna K, RENNIE, Ian G, GANESH, Anil and SISLEY, Karen (2003). Instability of microsatellites is an infrequent event in uveal melanoma. Melanoma Research, 13 (5), 435-440.
WOODWARD, Julia K L, ELSHAW, Shona R, MURRAY, Anna K, NICHOLS, Carmel E, CROSS, Neil, LAWS, David, RENNIE, Ian G and SISLEY, Karen (2002). Stimulation and inhibition of uveal melanoma invasion by HGF, GRO, IL-1alpha and TGF-beta. Investigative ophthalmology & visual science, 43 (10), 3144-3152.
CROSS, N A, KELLOCK, D J, KINGHORN, G R, TARAKTCHOGLOU, M, BATAKI, E, OXLEY, K M, HAWKEY, P M and ELEY, A (1999). Antimicrobial susceptibility testing of Chlamydia trachomatis using a reverse transcriptase PCR-based method. Antimicrobial agents and chemotherapy, 43 (9), 2311-2313.
Ieva Palubeckaite - Analysis of three dimensional cultured cells using mass spectrometry imaging
Amal Arhoma - Enhancement of Death receptor-mediated apoptosis on Multiple Myeloma
Rachel Doherty - The role of Cancer Stem Cells in uveal melanoma
Nicola Wright - Role of cancer stem cells in breast and prostate cancer
Abas Kokab - The role of Chlamydia trachomatis in male infertility (At UoS)
Are you sure you want to cancel your place on Saturday 12 November?