- Macrophages from human pluripotent stem cells September 24, 2018
- Genome editing in induced pluripotent stem cells rescues TAF1 levels in X-linked dystonia-parkinsonism September 7, 2018
- FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex August 30, 2018
- Variant U1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease August 1, 2018
- Multiplex High-Throughput Targeted Proteomic Assay to Identify Induced Pluripotent Stem Cells July 8, 2018
Head, James Martin Stem Cell Facility | firstname.lastname@example.org
Sally Cowley joined the Sir William Dunn School of Pathology as a Wellcome Trust Career Re-Entry Fellow in 2007, engaged in a program of research into the differentiation of human Pluripotent Stem Cell-derived macrophages and their applications for HIV studies. With William James, she set up the James Martin Stem Cell Facility, affiliated to the Oxford Stem Cell Institute, for work with human Pluripotent Stem cells.
Collaborative projects she works on within this facility include: iPSc-derived macrophages as a genetically-modifiable model system for understanding macrophage biology; developing iPSc-microglia to study the contribution of microglia to neurodegenerative disease; generating iPS cells from Parkinson’s Disease patients as part of a large scale Oxford Parkinson’s Disease Centre research programme funded by Parkinson’s UK; EU IMI StemBANCC, which established a panel of iPS derived cell lines from 500 patients as a platform for cellular phenotypic drug screening with industry partners; MRC DPUK Experimental Medicine Dementia Stem Cell Network, a UK-wide network (Oxford, Cambridge, UCL, Manchester, Cardiff, Edinburgh) using iPSc for modelling dementia.
A graduate of Natural Sciences at Cambridge, Sally’s began her research career working on host-pathogen interactions in mycobacteria (Ph.D, 1990, Royal College of Surgeons, University of London, and later at AHRI, Ethiopia). Her post-doctoral work (New England Deaconess Hospital, Boston, and Institute of Cancer Research, London) centred around signal transduction pathways involved in differentiation: She identified and cloned a novel tyrosine kinase, MATK (expressed predominantly in megakaryocytes and implicated in their differentiation [JBC 1994]); and was the first to demonstrate that the protein kinase MEK (/MKK) is downstream from the product of the important cancer associated genes Ras and Raf, and is critical for signal transduction pathways leading to differentiation and to tumorigenic transformation [Cell 1994 cited over 1800 times; EMBO J. 1994].
She chose to break from full-time lab-work whilst raising young children, continuing to tutor undergraduates part-time at the University of Oxford and the Open University. She subsequently obtained a Wellcome Trust Career Re-entry fellowship and joined the Sir William Dunn School of Pathology in 2007.
Information for prospective students
Enthusiastic, hardworking, able graduate students and University of Oxford undergraduate project students are welcome to enquire about potential projects. Details of current departmental D.Phil programmes are available on the Sir William Dunn School of Pathology website.
Primary Research Publications in Peer-Reviewed Journals
Proteolytic shedding of the prion protein via activation of metallopeptidase ADAM10 reduces cellular binding and toxicity of amyloid-β oligomers. Jarosz-Griffiths HH, Corbett NJ, Rowland HA, Fisher K, Jones AC, Baron J, Howell GJ, Cowley SA, Chintawar S, Cader MZ, Kellett KAB, Hooper NM. J Biol Chem. 2019 Mar 14.
Cellular α-synuclein pathology is associated with bioenergetic dysfunction in Parkinson’s iPSC-derived dopamine neurons. Zambon F, Cherubini M, Fernandes HJR, Lang C, Ryan BJ, Volpato V, Bengoa-Vergniory N, Vingill S, Attar M, Booth HDE, Haenseler W, Vowles J, Bowden R, Webber C, Cowley SA, Wade-Martins R. Hum Mol Genet. 2019 Feb 11.
Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes. Lang C, Campbell KR, Ryan BJ, Carling P, Attar M, Vowles J, Perestenko OV, Bowden R, Baig F, Kasten M, Hu MT, Cowley SA, Webber C, Wade-Martins R. Cell Stem Cell. 2019 Jan 3;24(1):93-106.e6
RIPK1 is a critical modulator of both tonic and TLR-responsive inflammatory and cell death pathways in human macrophage differentiation. Buchrieser J, Oliva-Martin MJ, Moore MD, Long JCD, Cowley SA, Perez-Simón JA, James W, Venero JL. Cell Death Dis. 2018 Sep 24;9(10):973.
Neurodegeneration in SCA14 is associated with increased PKCγ kinase activity, mislocalization and aggregation. Wong MMK, Hoekstra SD, Vowles J, Watson LM, Fuller G, Németh AH, Cowley SA, Ansorge O, Talbot K, Becker EBE. Acta Neuropathol Commun. 2018 Sep 24;6(1):99.
Genome editing in induced pluripotent stem cells rescues TAF1 levels in X-linked dystonia-parkinsonism. Rakovic A, Domingo A, Grütz K, Kulikovskaja L, Capetian P, Cowley SA, Lenz I, Brüggemann N, Rosales R, Jamora D, Rolfs A, Seibler P, Westenberger A, König I, Klein C. Mov Disord. 2018 Jul;33(7):1108-1118.
FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex. Künzel U, Grieve AG, Meng Y, Sieber B, Cowley SA, Freeman M. Elife. 2018 Jun 13;7.
LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages. Härtlova, A., Herbst, S., Peltier, J., Rodgers, A., Bilkei-Gorzo, O., Fearns, A., Dill, B. D., Lee, H., Flynn, R., Cowley, S. A., Davies, P., Lewis, P. A., Ganley, I. G., Martinez, J., Alessi, D. R., Reith, A. D., Trost, M., and Gutierrez, M. G. EMBO J. 2018 Jun 15;37(12)
Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1. Jonikas, M., Madill, M., Mathy, A., Zekoll, T., Zois, C. E., Wigfield, S., Kurzawa-Akanbi, M., Browne, C., Sims, D., Chinnery, P. F., Cowley, S. A., and Tofaris, G. K. Ann Neurol. 2018 May;83(5):915-925
A simplified method for generating purkinje cells from Human-Induced pluripotent stem cells. Watson, L. M., Wong, M. M. K., Vowles, J., Cowley, S. A., and Becker, E. B. E. Cerebellum. 2018 Aug;17(4):419-427
Heman-Ackah, S. M., Manzano, R., Hoozemans, J. J. M., Scheper, W., Flynn, R., Haerty, W., Cowley, S. A., Bassett, A. R., and Wood, M. J. A. (2017). Alpha-Synuclein induces the unfolded protein response in parkinson’s disease SNCA triplication iPSC-derived neurons. Human molecular genetics, 15;26(22):4441-4450.
Haenseler, W., Zambon, F., Lee, H., Vowles, J., Rinaldi, F., Duggal, G., Houlden, H., Gwinn, K., Wray, S., Luk, K. C., Wade-Martins, R., James, W. S., and Cowley, S. A. (2017). Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages. Scientific reports, 7(1).
Beevers, J. E., Lai, M. C. C., Collins, E., Booth, H. D. E., Zambon, F., Parkkinen, L., Vowles, J., Cowley, S. A., Wade-Martins, R., and Caffrey, T. M. (2017). MAPT genetic variation and neuronal maturity alter isoform expression affecting axonal transport in iPSC-derived dopamine neurons. Stem cell reports, 9(2):587-599.
Haenseler, W., Sansom, S. N., Buchrieser, J., Newey, S. E., Moore, C. S., Nicholls, F. J., Chintawar, S., Schnell, C., Antel, J. P., Allen, N. D., Cader, M. Z., Wade-Martins, R., James, W. S., and Cowley, S. A. (2017). A highly efficient human pluripotent stem cell microglia model displays a Neuronal-Co-culture-Specific expression profile and inflammatory response. Stem cell reports, 8(6):1727-1742.
Sandor, C., Robertson, P., Lang, C., Heger, A., Booth, H., Vowles, J., Witty, L., Bowden, R., Hu, M., Cowley, S.A., Wade-Martins, R. and Webber, C. (2017). Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson’s disease. Human molecular genetics.26(3):552-566.
Baud, A., Wessely, F., Mazzacuva, F., McCormick, J., Camuzeaux, S., Heywood, W., Little, D., Vowles, J., Tuefferd, M., Mosaku,O., Lako, M., Armstrong, L., Webber, C., Cader, M.Z., Peeters, P., Gissen, P., Cowley, S.A., and Mills, K.O. (2017). Multiplex High-Throughput Targeted Proteomic Assay To Identify Induced Pluripotent Stem Cells. Analytical chemistry 89, 2440-2448
Vazquez-Arango, P., Vowles, J., Browne, C., Hartfield, E., Fernandes, H. J., Mandefro, B., Sareen, D., James, W., Wade-Martins, R., Cowley, S. A., Murphy, S., and O’Reilly, D. (2016). Variant u1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease. Nucleic acids research. 44, 10960-10973.
Dafinca, R., Scaber, J., Ababneh, N., Lalic, T., Weir, G., Christian, H., Vowles, J., Douglas, A. G., Fletcher-Jones, A., Browne, C., Nakanishi, M., Turner, M. R., Wade-Martins, R., Cowley, S. A., and Talbot, K. (2016). C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem Cell-Derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal dementia. Stem cells (Dayton, Ohio), 34(8):2063-2078.
Kapellos, T. S., Taylor, L., Lee, H., Cowley, S. A., James, W. S., Iqbal, A. J., and Greaves, D. R. (2016). A novel real time imaging platform to quantify macrophage phagocytosis. Biochemical pharmacology. 116, 107-119.
Fernandes, H. J., Hartfield, E. M., Christian, H. C., Emmanoulidou, E., Zheng, Y., Booth, H., Bogetofte, H., Lang, C., Ryan, B. J., Sardi, S. P., Badger, J., Vowles, J., Evetts, S., Tofaris, G. K., Vekrellis, K., Talbot, K., Hu, M. T., James, W., Cowley, S. A., and Wade-Martins, R. (2016). ER stress and autophagic perturbations lead to elevated extracellular α-Synuclein in GBA-N370S parkinson’s iPSC-derived dopamine neurons. Stem cell reports, 6(3):342-356.
Handel, A. E., Chintawar, S., Lalic, T., Whiteley, E., Vowles, J., Giustacchini, A., Argoud, K., Sopp, P., Nakanishi, M., Bowden, R., Cowley, S., Newey, S., Akerman, C., Ponting, C. P., and Cader, M. Z. (2016). Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics. Human molecular genetics, 25(5):989-1000.
Flynn, R., Grundmann, A., Renz, P., Hänseler, W., James, W. S., Cowley, S. A., and Moore, M. D. (2015). CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells. Experimental hematology, 43(10).
van Wilgenburg B, Moore MD, James WS and Cowley SA (2014) The productive entry pathway of HIV-1 in macrophages is dependent on endocytosis through lipid rafts containing CD4. PLoS ONE DOI: 10.1371/journal.pone.0086071
Hartfield EM, Yamasaki-Mann M, Ribeiro Fernandes HJ, Vowles J, James WS, Cowley SA and Wade-Martins R. (2014). Physiological characterisation of human iPS-derived dopaminergic neurons. PloS one, 9(2):e87388+.
Wilgenburg Bv, Browne C, Vowles J, Cowley SA (2013) Efficient, Long Term Production of Monocyte-Derived Macrophages from Human Pluripotent Stem Cells under Partly-Defined and Fully-Defined Conditions. PLoS ONE 8(8): e71098. doi:10.1371/journal.pone.0071098
O’Reilly D, Dienstbier M, Cowley SA, Vazquez P, Drozdz M, Taylor S, James WS, and Murphy S. Differentially expressed, variant u1 snRNAs regulate gene expression in human cells. Genome research 2013, 23(2):281-291.
Jiang Y*, Cowley SA*, Siler U* , Melguzo D, Tilgner K, Browne C, deWilton A, Pryzborski S, Saretzki G,James WS, Reichenbach J, Seger RA, Lako M and Armstrong L. *joint first authors. Derivation and functional analysis of patient specific induced pluripotent stem cells as an in vitro model of Chronic Granulomatous Disease. Stem Cells 2012 30(4):599-611.
Raposo RASA, Trudgian DC, Thomas B, van Wilgenburg B, Cowley SA and James W. Protein Kinase C and NF-κB-dependent CD4 downregulation in macrophages induced by t cell-derived soluble factors: consequences for HIV-1 infection. Journal of immunology 2011 187(2):748-759.
Zhou L, Sokolskaja E, Jolly C, James W, Cowley SA and Fassati A. Transportin 3 Promotes a Nuclear Maturation Step Required for Efficient HIV-1 Integration. PLoS Pathogens 2011 7(8):e1002194+.
Mandegar MA, MoralliD, KhojaS, Cowley S, ChanDY, YusufM, MukherjeeS, Blundell MP, VolpiEV, ThrasherAJ, JamesW and Monaco ZL. Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells. Human Molecular Genetics 2011 20(15):2905-2913
Xu X, Cowley S, Flaim CJ, James W, Seymour LW and Cui Z. The role of apoptotic pathways in the low recovery rate after cryopreservation of dissociated human embryonic stem cells. Biotechnology progress 2010 26(3):827-837
Xu X, Cowley S, Flaim CJ, James W, Seymour LW and Cui Z. Enhancement of cell recovery for dissociated human embryonic stem cells after cryopreservation. Biotechnology progress 2010 26(3):781-788
Brook FA, Cowley SA, Evans EP, Turner K, James WS and Mardon HJ. Derivation and characterization of the human embryonic stem cell line, OxF1. In Vitro Cellular and Developmental Biology – Animal 2010 46(3-4):173-177
Karlsson KR, Cowley S, Martinez FO, Shaw M, Minger SL, and James W. Homogeneous monocytes and macrophages from human embryonic stem cells following coculture-free differentiation in M-CSF and IL-3. Experimental Hematology 2008 36 1167–1175
Mache A, Mengistu Y and Cowley S. Shigella serogroups identified from adult diarrhoeal out-patients in Addis Ababa, Ethiopia: antibiotic resistance and plasmid profile analysis. East African Medical Journal 1997 74 179-182.
Mache A, Mengistu Y and Cowley S. Salmonella serogroups identified from adult diarrhoeal out-patients in Addis Ababa, Ethiopia: antibiotic resistance and plasmid profile analysis. East African Medical Journal 1997 74 183-186.
Alessi DR, Cohen P, Ashworth A, Cowley S, Leevers SJ, Marshall CJ. Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf. Methods in Enzymology 1995 255 279-90.
Towatari M, May GE, Marais R, Perkins G, Marshall CJ, Cowley S and Enver T. Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin- 3. Journal of Biological Chemistry 1995 270 4101-4107.
Gillespie-Brown J, Fuller SJ, Bogoyevitch MA, Cowley S, Sugden PH. The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. Journal of Biological Chemistry 1995 270 28092-6.
Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J and Saklatvala J. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of hsp27. Cell 1994 78 1039-1049.
Cowley S, Paterson H, Kemp P and Marshall CJ. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 1994 77 841-852.
Alessi DR, Saito Y, Campbell DG, Cohen P, Sithanandam G, Rapp U, Ashworth A, Marshall CJ and Cowley S. Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1. EMBO J. 1994 13 1610-1619.
Bennett BD*, Cowley S*, Jiang S, London R, Deng B, Grabarek J, Groopman JE, Goeddel DV, Avraham H. *joint first authors. Identification and characterization of a novel tyrosine kinase from megakaryocytes. Journal of Biological Chemistry 1994 269 1068-1074.
Avraham H, Cowley S, Chi SY, Jiang S, Groopman JE. Characterization of adhesive interactions between human endothelial cells and megakaryocytes. Journal of Clinical Investigation 1993 93 2378-84.
Cowley SA, Groopman JE, Avraham H. Effects of transforming growth factor beta on megakaryocytic cell fusion and endomitosis. International Journal of Cell Cloning 1992 10 223-231.
Avraham H, Vannier E, Cowley SA, Jiang S, Chi S, Dinarello CA, Zsebo KM, Groopman JE. Effects of stem cell factor, c-kit ligand, on human megakaryocytic cells. Blood 1992 79365-71.
Gschmeissner SE, Pereira JH, Cowley SA. Rapid assessment of nerve stumps. Journal of Bone and Joint Surgery 1991 73 688-89.
Pereira JH, Cowley SA, Gschmeissner SE, Bowden REM, Turk JL. Denatured muscle grafts for nerve repair: an experimental model of nerve damage in leprosy. Journal of Bone and Joint Surgery 1990 72 874-80.
Cowley SA, Gschmeissner SE, Negesse Y, Curtis J, Turk JL. Major Histocompatibility Complex Class II antigen expression in nerves in leprosy. An immuno-electron microscopical study. International Journal of Leprosy and other Mycobacterial diseases 1990 58 560-565.
Cowley SA, Butter C, Gschmeissner SE, Curtis J, Turk JL. An immuno-electron microscopical study of the expression of MHC Class II antigens in guinea pig sciatic nerves following induction of intraneural granulomas. Journal of Neuroimmunology 1989 33 223-231.
Cowley SA, Butter C, Verghese S, Curtis J, Turk JL. Nerve damage induced by mycobacterial granulomas in guinea pig sciatic nerves. International Journal of Leprosy and other Mycobacterial diseases 1988 56 283-290.
Book Chapters and Reviews
Microglial inflammation and phagocytosis in Alzheimer’s disease: potential therapeutic targets. Nizami S, Hall-Roberts H, Warrier S, Cowley SA, Di Daniel E. Br J Pharmacol. 2019 Feb 10.
Lee, H., James, W. S., and Cowley, S.A. (2017). LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson’s disease. Biochemical Society transactions 45, 131-139.
Dodsworth, B. T., Flynn, R., and Cowley, S. A. (2015). The current state of naïve human pluripotency. Stem cells (Dayton, Ohio), 33(11):3181-3186.
Hartfield, E. M., Fernandes, H. J., Vowles, J., Cowley, S. A., and Wade-Martins, R. (2012). Cellular reprogramming: a new approach to modelling parkinson’s disease. Biochemical Society transactions, 40(5):1152-1157.
Cowley, S. A., Karlsson, K. R., van Wilgenburg, B., Carter, G., Browne, C., Vowles, J., Martinez Estrada, F., Pelchen-Matthews, A., Miller, J., Moore, M. D., and James, W. (2012). Macrophages from human Pluripotent Stem Cells. Chapter 3 in Handbook of Macrophages: Life Cycle, Functions and Diseases, pages 83-120. Nova Science Publishers, NY. ISBN: 978-1-62081-162-7
Cowley S Induced pluripotent stem cells and their application into personalised therapy. Chapter in: Comprehensive Biotechnology 2nd Edition. Elsevier. 2011 ISBN 13: 978-0-444-53352-4
Lufino M M P, Popplestone, AR, Cowley SA, Edser PAH, James WS and Wade-Martins R. Episomal transgene expression in pluripotent stem cells. Methods in Molecular Biology 2011 767(27): 369-387. Humana Press, Totowa, NJ.
Cowley S and Romero I. Signal Transduction. Chapter in Molecular and Cell Biology 2004 Open University Press, Milton Keynes.
Cowley S and Romero I. Tumorigenesis. Chapter in Molecular and Cell Biology 2004 Open University Press, Milton Keynes.