David Onion

Contact

• workRoom E108 Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work0115 82 30736
• david.onion@nottingham.ac.uk
• www.nottingham.ac.uk/life-sciences/facilities/flow-cytometry-facility/index.aspx

Biography

I am a research scientist with 20 year's experience in the fields of Cancer and Immunology. My research focuses on the influence of the tumor microenvironment on tumour cell biology and sensitivity to chemotherapy. I have particular expertise in ex vivo models and cytometry and I manage the University of Nottingham Flow Cytometry Facility.

Expertise Summary

My career long use of flow cytometry as a tool to measure immune-oncology, the tumour microenvironment, immune responses to cancer gene therapy vectors and to develop immunotherapeutics has led a number of basic research contributions and to the advancement of research technology. I also day-to-day leverage this experience to advance and extend the use of flow cytometric technology to many areas of research at the University of Nottingham.

My extensive experience in developing novel model systems and novel ways to measure immune-pathogen and immune-cancer cell interactions has led to new ways to fluorescently label and investigate virus binding and sub-cellular trafficking using Imaging cytometry, flow cytometry and conventional confocal microscopy. These have fed in to the advancement adenoviral cancer gene therapy vectors currently under clinical investigation. I developed an array of immune-assays that have led to a significant contribution to the understanding of how vector immune responses influence the efficacy of viral vectors in the clinical setting of both cancer gene therapy and vaccine fields. The subsequent understanding of immune control of adenovirus replication has also led to the advancement of immunotherapies for the treatment of adenovirus infection in paediatric stem cell transplantation recipients.

My current focus is on the refinement and development of pre-clinical tumour models, which are more reflective of the human disease and hence better able to predict patient efficacy. With a particular focus on the tumour microenvironment of Non-Small Cell Lung and Oesophageal Cancer, I have developed a unique 3D assay that can incorporate patient derived tumour cells as well as the ancillary cells of the tumour microenvironment and have demonstrated accurate prediction of patient sensitivity to chemotherapeutics. This has resulted in advancement in the understanding of resistance to chemotherapy in the setting of NSCLC and also a potential new way to determine whether a patient would be benefit from chemotherapy in oesophageal cancer.

Recent Publications

• NASIR, A., CARDALL, A., OTHMAN, R. T., NICOLAOU, N., LOURDUSAMY, A., LINKE, F., ONION, D., RYZHOVA, M., CAMERON, H., VALENTE, C., RITCHIE, A., KORSHUNOV, A., PFISTER, S. M., GRABOWSKA, A. M., KERR, I. D. and COYLE, B., 2021. ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma: Neurooncol Adv Neurooncol Adv. 3(1), vdab030
• ARAM, J., FRAKICH, N., MORANDI, E., ALROUJI, M., SAMARAWEERA, A., ONION, D., SPENDLOVE, I., COLOMBO, S. L., TANASESCU, R., GRAN, B. and CONSTANTINESCU, C. S., 2020. Increased IL-2 and Reduced TGF-beta Upon T-Cell Stimulation are Associated with GM-CSF Upregulation in Multiple Immune Cell Types in Multiple Sclerosis: Biomedicines Biomedicines. 8(7),
• PAL, A., ASHWORTH, J. C., COLLIER, P., PROBERT, C., JONES, S., LEZA, E. P., MEAKIN, M. L., A. RITCHIE A, ONION, D., CLARKE, P. A., ALLEGRUCCI, C. and GRABOWSKA, A. M., 2020. A 3D Heterotypic Breast Cancer Model Demonstrates a Role for Mesenchymal Stem Cells in Driving a Proliferative and Invasive Phenotype: Cancers (Basel) Cancers (Basel). 12(8),
• SMITH, S. J., ROWLINSON, J., ESTEVEZ-CEBRERO, M., ONION, D., RITCHIE, A., CLARKE, P., WOOD, K., DIKSIN, M., LOURDUSAMY, A., GRUNDY, R. G. and RAHMAN, R., 2020. Metabolism-based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential: Neurooncol Adv Neurooncol Adv. 2(1), vdaa087

• View all publications

• NASIR, A., CARDALL, A., OTHMAN, R. T., NICOLAOU, N., LOURDUSAMY, A., LINKE, F., ONION, D., RYZHOVA, M., CAMERON, H., VALENTE, C., RITCHIE, A., KORSHUNOV, A., PFISTER, S. M., GRABOWSKA, A. M., KERR, I. D. and COYLE, B., 2021. ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma: Neurooncol Adv Neurooncol Adv. 3(1), vdab030
• ARAM, J., FRAKICH, N., MORANDI, E., ALROUJI, M., SAMARAWEERA, A., ONION, D., SPENDLOVE, I., COLOMBO, S. L., TANASESCU, R., GRAN, B. and CONSTANTINESCU, C. S., 2020. Increased IL-2 and Reduced TGF-beta Upon T-Cell Stimulation are Associated with GM-CSF Upregulation in Multiple Immune Cell Types in Multiple Sclerosis: Biomedicines Biomedicines. 8(7),
• PAL, A., ASHWORTH, J. C., COLLIER, P., PROBERT, C., JONES, S., LEZA, E. P., MEAKIN, M. L., A. RITCHIE A, ONION, D., CLARKE, P. A., ALLEGRUCCI, C. and GRABOWSKA, A. M., 2020. A 3D Heterotypic Breast Cancer Model Demonstrates a Role for Mesenchymal Stem Cells in Driving a Proliferative and Invasive Phenotype: Cancers (Basel) Cancers (Basel). 12(8),
• SMITH, S. J., ROWLINSON, J., ESTEVEZ-CEBRERO, M., ONION, D., RITCHIE, A., CLARKE, P., WOOD, K., DIKSIN, M., LOURDUSAMY, A., GRUNDY, R. G. and RAHMAN, R., 2020. Metabolism-based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential: Neurooncol Adv Neurooncol Adv. 2(1), vdaa087
• TANASESCU, R., TENCH, C. R., CONSTANTINESCU, C. S., TELFORD, G., SINGH, S., FRAKICH, N., ONION, D., AUER, D. P., GRAN, B., EVANGELOU, N., FALAH, Y., RANSHAW, C., CANTACESSI, C., JENKINS, T. P. and PRITCHARD, D. I., 2020. Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial: JAMA Neurol JAMA Neurol. 77(9), 1089-1098
• ALI, EMAN ALI, KALLI, MARINA, WAN, DANIEL, NAKAMURA, RYOSUKE, ONION, DAVID, ALANINE, DANIEL G. W., ALCOCER, MARCOS J. C. and FALCONE, FRANCO H., 2019. Characterization of human FcεRIα chain expression and gene copy number in humanized rat basophilic leukaemia (RBL) reporter cell lines: PLOS ONE PLoS One. 14(8), e0221034
• HARRISON, RICHARD P., CHAUHAN, VEEREN M., ONION, DAVID, AYLOTT, JONATHAN W. and SOTTILE, VIRGINIE, 2019. Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells: RSC Advances Rsc Advances. 9(6), 3176-3184
• HOSSAIN,MD JAKIR, MORANDI,ELENA, TANASESCU,RADU, FRAKICH,NANCI, CALDANO,MARZIA, ONION,DAVID, FARAJ,TOLA A., ERRIDGE,CLETT and GRAN,BRUNO, 2018. The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker: Frontiers in Immunology Front Immunol. 9(457),
• ONION, D., ISHERWOOD, M., SHRIDHAR, N., XENOPHONTOS, M., CRAZE, M. L., DAY, L. J., GARCIA-MARQUEZ, M. A., PINEDA, R. G., REECE-SMITH, A. M., SAUNDERS, J. H., DUFFY, J. P., ARGENT, R. H. and GRABOWSKA, A. M., 2018. Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer: Oncotarget Oncotarget. 9(2), 1760-1771
• SINGH, SONALI, AWUAH, DENNIS, ROSTAM, HASSAN M., EMES, RICHARD D., KANDOLA, NAVROHIT K., ONION, DAVID, HTWE, SU SU, RAJCHAGOOL, BUDDHARAKSA, CHA, BYUNG-HYUN, KIM, DUCKJIN, TIGHE, PATRICK J., VRANA, NIHAL E., KHADEMHOSSEINI, ALI and GHAEMMAGHAMI, AMIR, 2017. Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States: ACS Biomaterials Science & Engineering ACS Biomaterials Science & Engineering. 3(6), 969-978
• ONION D, ARGENT RH, REECE-SMITH AM, CRAZE ML, PINEDA RG, CLARKE PA, RATAN HL, PARSONS SL, LOBO DN, DUFFY JP, ATHERTON JC, MCKENZIE AJ, KUMARI R, KING P, HALL BM and GRABOWSKA AM, 2016. 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors. Molecular cancer therapeutics. 15(4), 753-63
• SAUNDERS JH, ONION D, COLLIER P, DORRINGTON MS, ARGENT RH, CLARKE PA, REECE-SMITH AM, PARSONS SL and GRABOWSKA AM, 2016. Individual patient oesophageal cancer 3D models for tailored treatment. Oncotarget.
• HEROD MR, PINEDA RG, MAUTNER V and ONION D, 2014. Quantum Dot Labelling of Adenovirus Allows Highly Sensitive Single Cell Flow and Imaging Cytometry. Small (Weinheim an der Bergstrasse, Germany). (In Press.)
• CHAKUPURAKAL G, ONION D, BONNEY S, COBBOLD M, MAUTNER V and MOSS P, 2013. HLA-peptide multimer selection of adenovirus-specific T cells for adoptive T-cell therapy. Journal of immunotherapy (Hagerstown, Md. : 1997). 36(8), 423-31
• DEACON, K., ONION, D., KUMARI, R., WATSON, S.A. and KNOX, A.J., 2012. Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer Journal of Biological Chemistry. 287(47), 39967-39981
• CHAKUPURAKAL, GEOTHY, ONION, DAVID, COBBOLD, MARK, MAUTNER, VIVIEN and MOSS, PAUL A H, 2010. Adenovirus vector-specific T cells demonstrate a unique memory phenotype with high proliferative potential and coexpression of CCR5 and integrin alpha4beta7. AIDS (London, England). 24(2), 205-10
• ONION, DAVID, PATEL, PRASHANT, PINEDA, ROBERT G, JAMES, NICHOLAS and MAUTNER, VIVIEN, 2009. Antivector and tumor immune responses following adenovirus-directed enzyme prodrug therapy for the treatment of prostate cancer. Human gene therapy. 20(11), 1249-58
• BRUTON, R K, RASTI, M, MAPP, K L, YOUNG, N, CARTER, R Z, ABRAMOWICZ, I A, SEDGWICK, G G, ONION, D F, SHUEN, M, MYMRYK, J S, TURNELL, A S and GRAND, R J A, 2007. C-terminal-binding protein interacting protein binds directly to adenovirus early region 1A through its N-terminal region and conserved region 3. Oncogene. 26(53), 7467-79
• ONION, DAVID, CROMPTON, LAURA J, MILLIGAN, DONALD W, MOSS, PAUL A H, LEE, STEVEN P and MAUTNER, VIVIEN, 2007. The CD4+ T-cell response to adenovirus is focused against conserved residues within the hexon protein. The Journal of general virology. 88(Pt 9), 2417-25
• LYONS, MARK, ONION, DAVID, GREEN, NICKY K, ASLAN, KRISS, RAJARATNAM, RATNA, BAZAN-PEREGRINO, MIRIAM, PHIPPS, SUE, HALE, SARAH, MAUTNER, VIVIEN, SEYMOUR, LEONARD W and FISHER, KERRY D, 2006. Adenovirus type 5 interactions with human blood cells may compromise systemic delivery. Molecular therapy : the journal of the American Society of Gene Therapy. 14(1), 118-28
• YOUNG, LAWRENCE S, SEARLE, PETER F, ONION, DAVID and MAUTNER, VIVIEN, 2006. Viral gene therapy strategies: from basic science to clinical application. The Journal of pathology. 208(2), 299-318
• SEYMOUR, L W, FISHER, K D, GREEN, N K, HALE, S J, LYONS, M, MAUTNER, V, NICUM, S, ONION, D, OUPICKY, D, STEVENSON, M and ULBRICH, K, 2003. Adenovirus retargeting and systemic delivery. Ernst Schering Research Foundation workshop. 107-14
• RIVETT, A JENNIFER, BOSE, SUCHIRA, PEMBERTON, ALEXANDER J, BROOKS, PAUL, ONION, DAVID, SHIRLEY, DAVID, STRATFORD, FIONA L L and FORTI, KATIA, Assays of proteasome activity in relation to aging. Experimental gerontology. 37(10-11), 1217-22