Dr Neil Cross is a Reader in Cancer Biology at Sheffield Hallam University. He completed a BSc in Biomedical Chemistry at Sheffield Hallam University prior to undertaking a PhD and several post-doctoral research positions in cancer biology at The University of Sheffield.
Neil is course leader for BSc Human Biology and teaches aspects of molecular biology and cellular biology particularly in relation to a disease mechanisms context.
His research interests are interdisciplinary projects focussed around cancer biology, and he uses this research to inform his teaching.
Course leader for BSc Human Biology
Neil is module leader for 1st year Topics in Human Biology module, and 2nd year Advanced Cell Biology, and contributes to teaching at all levels of undergraduate teaching including 1st year Human Reproduction and Development, 2nd year Biomedical Investigative Techniques and 3rd year Cell Pathology and Infection. At post-graduate level, he is module leader for Cellular and Molecular Basis of Cancer, and Molecular Diagnostics. He also supervises research projects at undergraduate and post-graduate level.
1) 3D cell culture models
Recent studies funded by NC3Rs and InnovateUK have focused on the development of in vitro alternatives to animal testing using 3D cell culture models. These 3D tumour spheroids mimic many of the biochemical features of tumours such as hypoxia, attenuated drug delivery and low glucose and growth factor levels. Previous work for NC3Rs focused on performing MALDI Mass Spectrometry imaging of small molecules and drugs in these 3D cultures from both cancer, and artificial skin models. Work funded by InnovateUK in collaboration with Asterand Inc. involves developing improved in vitro testing methodologies which may replace patient-derived xenograft/animal testing, by culturing primary human cancer cells in 3D cell culture, allowing drug sensitivity testing to be performed on tumour tissue. This work is in collaboration with Dr Graham Place, Asterand Inc. Related studies with Prof. Malcolm Clench at SHU are using these 3D cell culture models to validate novel methods of quantification of Mass Spectrometry Imaging of proteins within in vitro tissue models.
2) Enhancement of Death Receptor-mediated apoptosis
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). 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 both Histone methytransferases and nuclear export inhibitors in particular can potently enhance tumour cell sensitivity to TRAIL in a range of tumour cells, and that these effects are more potent in 3D cell culture. This work is in collaboration with Dr Andy Chantry, University of Sheffield.
3) Role of cancer stem cells in tumour development and drug resistance
Recent evidence suggests that tumours 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 our studies, we have identified a quiescent/non-dividing population which are intrinsically drug-insensitive and may mediate drug resistance. We are investigating the origin and clinical relevance of these cells in terms of mediating drug resistance and potentially disease metastasis. This work is in collaboration with Dr Colby Eaton and Dr Ning Wang, University of Sheffield.
Ongoing studies in Uveal melanoma are investigating the phenomenon of phenotypic plasticity in terms of reversible differentiation/dedifferentiation which has direct links to the cancer stem cell hypothesis. These studies are in collaboration with Dr Karen Sisley at University of Sheffield.
Furthermore, our studies in breast and prostate stem cell-like cells have demonstrated potent anti-tumour activity of a series of Withanolide-derived compounds which closely resemble androgen-precursors, and these show activity in hormone-dependent cancer cell lines. This work is in collaboration with Dr Tom Sayers, National Institutes of Health, USA.
4) Mitochondrial targeting of anti-tumour agents
The mitochondria are a potential target for anti-tumour agents due to a) their central role in energy dependency and b) their role in regulating apoptosis. Cancer cells have an increased mitochondrial membrane potential vs. normal cells, allowing their selective targeting by lipophilic cations. We have used phosphonium-based conjugation to allow targeting of molecules to the mitochondrion, initially focusing on gold nanoparticles as a cargo. This allows photo-thermal therapy via exposure of specific wavelengths of light, which excite the gold nanoparticles, resulting in mitochondrial release of pro-apoptotic factors. Proof of principle experiments show that a) gold nanoparticles is concentrated in the mitochondria and b) photothermal therapy is enhances in the presence of phosphonium-conjugated gold nanoparticles. This work is in collaboration with Prof. Neil Bricklebank at Sheffield Hallam University.
- Dr Andy Chantry, Mellanby Centre for Bone Biology, University of Sheffield
- Dr Graham Place, Asterand Inc, Royston, UK
- Dr Tom Sayers, National Cancer Institute, National Institutes of Health, USA
- Dr Colby Eaton and Dr Ning Wang, Academic Urology Unit, University of Sheffield
- Dr Karen Sisley, Department of Ophthalmology and Orthoptics, University of Sheffield Medical School
- National Centre for Reduction, Refinement and Replacement of Animals in Research (Nc3Rs)
- Yorkshire Cancer Research
- Bone Cancer Research Trust
- Weston Park Hospital Cancer Appeal
- International Centre for Studies and Research in Biomedicine (ICB)
- Biomolecular 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, 104877-104893.
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.
Dr Cross is a member of the University validation panels, assessing new course provision at course approval events. He is also a specialist scientific reviewer for InnovateUK.
- Ieva Palubeckaite - Analysis of three dimensional cell cultures using mass spectrometry imaging
- Imran Jabbar - Modelling Human Chorionic Gonadotropin Immunoassay for Treatment Response in Low-Risk Gestational Trophoblastic Neoplasia
- Lucy Flint - Biopharmaceutical Quantification by Mass Spectrometry Imaging
Previous PhD students:
- Amal Arhoma - Enhancement of Death receptor-mediated apoptosis on Multiple Myeloma
- Nikhil Lalwani - Triphenylarsonium-functionalised gold nanoparticles: Potential nanocarriers for intracellular therapeutics.
- Nicola Wright - Role of cancer stem cells in breast and prostate cancer.
- Amani Mahbub - The anti-cancer potentials of polyphenols in the treatment of leukemia.
- Jenni Chen -Phosphonium-functionalised gold nanoparticles for mitochondrial-targeted therapeutics
- Rachel Doherty - The role of Cancer Stem Cells in uveal melanoma.
- Abas Kokab - The role of Chlamydia trachomatis in male infertility.
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