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研究领域

1. Medical device development: Bioreactors for manufacture of stem-cell derived products Scaling from lab to clinic will require more efficient methods to propagate stem cells, direct differentiation and utilise expensive culture components such as cytokines and adhesion molecules. At the present time there are no cost-effective ways of producing transfusion products from blood stem cells. We have developed a bioreactor system with micro-channel (200 micron) architecture, to support high-density growth of haematopoietic cells (1-100 million cells/ml) in a low fluid shear environment. Future work will employ microfluidic manufacturing technology to develop microbioreactors for process optimisation. This is a multidisplinary program that draws on biomedical, electrical, mechanical and chemical engineering disciplines. 2. Lineage fate mapping by high-throughput live cell imaging. We are developing lab-on-a-chip devices for high throughput mapping of cell fate. These include microwell devices (shown above) for study of clonal development, as well as perfusion devices that simulate steady and pulsatile flow. We are currently using time-lapse video microscopy to track blood, endothelial and cardiac development. 3. Mathematical biology: Stochastic modeling of multipotent cell fate decisions Current understanding of multipotent cell fate is based on the culture of highly purified cell subsets and transplantation studies. Cell division and differentiation events are asynchronous. Precursor cells undergo multiple rounds of cell division and developmental stages before reaching a terminally differentiated cell type. To establish the relatedness of multipotent cells and their progeny it is necessary to keep track of lineage development. We have developed a flow cytometric approach to track cell division in vitro or in vivo. Cell generation number (number of mitoses) can be determined in addition to cell phenotype. This data is used to mathematically reconstruct cell differentiation pathways.

近期论文

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Dolnikov A; Yang S; Shen S; Xu N; Chaudhry K; Nordon R; O'Brien T, 2016, 'PROLONGING CART CELL PERSISTENCE USING CONDITIONING WITH 5-AZACYTIDINE', Cytotherapy, vol. 18, no. 6, pp. S61 - S61, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000376222800163&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a Cornwell JA; Hallett RM; Der Mauer SA; Motazedian A; Schroeder T; Draper JS; Harvey RP; Nordon RE, 2016, 'Quantifying intrinsic and extrinsic control of single-cell fates in cancer and stem/progenitor cell pedigrees with competing risks analysis', Scientific Reports, vol. 6, http://dx.doi.org/10.1038/srep27100 Weiss DJ; Rasko JEJ; Cuende N; Ruiz MA; Ho HN; Nordon R; Wilton S; Dominici M; Srivastava A, 2016, 'Part 2: Making the "unproven" "proven"', Cytotherapy, vol. 18, no. 1, pp. 120 - 123, http://dx.doi.org/10.1016/j.jcyt.2015.11.005 Dominici M; Nichols K; Srivastava A; Weiss DJ; Eldridge P; Cuende N; Deans RJ; Rasko JEJ; Levine AD; Turner L; Griffin DL; O'Donnell L; Forte M; Mason C; Wagena E; Janssen W; Nordon R; Wall D; Ho HN; Ruiz MA; Wilton S; Horwitz EM; Gunter KC, 2015, 'Positioning a Scientific Community on Unproven Cellular Therapies: The 2015 International Society for Cellular Therapy Perspective', Cytotherapy, vol. 17, no. 12, pp. 1663 - 1666, http://dx.doi.org/10.1016/j.jcyt.2015.10.007 Hallett RM; Huang C; Motazedian A; Der Mauer SA; Pond GR; Hassell JA; Nordon RE; Draper JS, 2015, 'Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy', Oncotarget, vol. 6, no. 9, pp. 7040 - 7052 Christo SN; Diener KR; Nordon RE; Brown MP; Griesser HJ; Vasilev K; Christo FC; Hayball JD, 2015, 'Scrutinizing calcium flux oscillations in T lymphocytes to deduce the strength of stimulus', Scientific Reports, vol. 5, http://dx.doi.org/10.1038/srep07760 Nordon RE; Cornwell J; Li J; Harvey RP; Schroeder T, 2013, 'MAPPING AND MODELLING EX VIVO CELL CULTURE PROCESSES DIRECTLY FROM CELL TRACKING DATA', Cytotherapy, vol. 15, no. 4, pp. S7 - S7, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000316535700012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a Chen H; Cornwell J; Zhang H; Lim T; Resurreccion R; Port T; Rosengarten G; Nordon RE, 2013, 'Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale', Lab On a Chip: microfluidic and nanotechnologies for chemistry, biology, and bioengineering, vol. 13, no. 15, pp. 2999 - 3007, http://dx.doi.org/10.1039/c3lc50123j Chen H; Rosengarten G; Li M; Nordon RE, 2012, 'Design of microdevices for long-term live cell imaging', Journal of Micromechanics and Microengineering, vol. 22, no. 6, pp. 065033 - 065033, http://dx.doi.org/10.1088/0960-1317/22/6/065033 Holmes T; Yan F; Ko KH; Nordon R; Song E; O'Brien TA; Dolnikov A, 2012, 'Ex vivo expansion of cord blood progenitors impairs their short-term and long-term repopulating activity associated with transcriptional dysregulation of signalling networks', Cell Proliferation: in basic and clinical sciences, vol. 45, no. 3, pp. 266 - 278, http://dx.doi.org/10.1111/j.1365-2184.2012.00813.x Ko KH; Holmes T; Palladinetti P; Song E; Nordon R; O'Brien TA; Dolnikov A, 2011, 'GSK-3β inhibition promotes engraftment of ex vivo-expanded hematopoietic stem cells and modulates gene expression', Stem Cells, vol. 29, no. 1, pp. 108 - 118, http://dx.doi.org/10.1002/stem.551 Irhimeh MR; Fitton JH; Ko KH; Lowenthal RM; Nordon RE, 2011, 'Formation of an adherent hematopoietic expansion culture using fucoidan', Annals of Hematology, vol. 90, no. 9, pp. 1005 - 1015, http://dx.doi.org/10.1007/s00277-011-1185-4 Nordon RE; Ko KH; Odell R; Schroeder T, 2011, 'Multi-type branching models to describe cell differentiation programs', Journal of Theoretical Biology, vol. 277, no. 1, pp. 7 - 18, http://dx.doi.org/10.1016/j.jtbi.2011.02.006 Nordon RE; Craig SJ; Foong FC, 2009, 'Molecular engineering of the cellulosome complex for affinity and bioenergy applications', Biotechnology Letters, vol. 31, no. 4, pp. 465 - 476, http://dx.doi.org/10.1007/s10529-008-9899-7 Godara P; Nordon RE; McFarland CD, 2008, 'Mesenchymal stem cells in tissue engineering', Journal of Chemical Technology and Biotechnology, vol. 83, no. 4, pp. 397 - 407, http://dx.doi.org/10.1002/jctb.1901 Godara P; McFarland CD; Nordon RE, 2008, 'Design of bioreactors for mesenchymal stem cell tissue engineering', Journal of Chemical Technology and Biotechnology, vol. 83, no. 4, pp. 408 - 420, http://dx.doi.org/10.1002/jctb.1918 Nordon RE; Craig S, 2007, 'Hollow-fibre affinity cell separation', Advances in Biochemical Engineering/Biotechnology, vol. 106, pp. 129 - 150, http://dx.doi.org/10.1007/10_2006_041 Nordon RE; Craig S, 2007, 'Hollow-fibre affinity cell separation.', Advances in Biochemical Engineering/Biotechnology, vol. 106, pp. 129 - 150 Ko KH; Odell R; Nordon RE, 2007, 'Analysis of cell differentiation by division tracking cytometry', Cytometry Part A, vol. 71, no. 10, pp. 773 - 782, http://dx.doi.org/10.1002/cyto.a.20437 Craig SJ; Shu A; Xu Y; Foong FC; Nordon R, 2007, 'Chimeric protein for selective cell attachment onto cellulosic substrates', Protein Engineering Design and Selection, vol. 20, no. 5, pp. 235 - 241, http://dx.doi.org/10.1093/protein/gzm016

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