ZFIN ID: ZDB-PERS-000913-2
Fleming, Angeleen
Email: af425@cam.ac.uk
Affiliation: Fleming Lab
Address: Department of Medical Genetics Cambridge Institute for Medical Research Wellcome/MRC Building Addenbrooke’s Hospital Hills Road Cambridge, CB2 2XY United Kingdom AND Department of Physiology, Development and Neuroscience (PDN) University of Cambridge Downing Street Cambridge, CB2 3EG United Kingdom
Country: United Kingdom

Disease modelling in zebrafish, in particular, neurodegenerative disease, blindness, bone biology disorders, behavioural screens.

Chemical library screens for disease rescue.

Fleming, A., Xuan, L.Z., Sanchez-Elexpuru, G., Williams, S.V., Windell, D., Gelb, M.H., Herbst, Z.M., Schlotawa, L., Rubinsztein, D.C. (2022) Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency. Frontiers in cell and developmental biology. 10:843079
Lopez, A., Gorb, A., Palha, N., Fleming, A., Rubinsztein, D.C. (2022) A New Zebrafish Model to Measure Neuronal α-Synuclein Clearance In Vivo. Genes. 13(5)
Iqbal, A., Baldrighi, M., Murdoch, J.N., Fleming, A., Wilkinson, C.J. (2020) Alpha-synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome. Biology Open. 9(10):
VerPlank, J.J.S., Tyrkalska, S.D., Fleming, A., Rubinsztein, D.C., Goldberg, A.L. (2020) cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases. Proceedings of the National Academy of Sciences of the United States of America. 117(25):14220-14230
Prajsnar, T.K., Serba, J.J., Dekker, B.M., Gibson, J.F., Masud, S., Fleming, A., Johnston, S.A., Renshaw, S.A., Meijer, A.H. (2020) The autophagic response to Staphylococcus aureus provides an intracellular niche in neutrophils. Autophagy. 17(4):888-902
Siddiqi, F.H., Menzies, F.M., Lopez, A., Stamatakou, E., Karabiyik, C., Ureshino, R., Ricketts, T., Jimenez-Sanchez, M., Esteban, M.A., Lai, L., Tortorella, M.D., Luo, Z., Liu, H., Metzakopian, E., Fernandes, H.J.R., Bassett, A., Karran, E., Miller, B.L., Fleming, A., Rubinsztein, D.C. (2019) Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing. Nature communications. 10:1817
Lopez, A., Fleming, A., Rubinsztein, D.C. (2018) Seeing is believing: methods to monitor vertebrate autophagy in vivo.. Open Biology. 8(10)
Foulkes, M.J., Henry, K.M., Rougeot, J., Hooper-Greenhill, E., Loynes, C.A., Jeffrey, P., Fleming, A., Savage, C.O., Meijer, A.H., Jones, S., Renshaw, S.A. (2017) Expression and regulation of drug transporters in vertebrate neutrophils. Scientific Reports. 7:4967
Lopez, A., Lee, S.E., Wojta, K., Ramos, E.M., Klein, E., Chen, J., Boxer, A.L., Gorno-Tempini, M.L., Geschwind, D.H., Schlotawa, L., Ogryzko, N.V., Bigio, E.H., Rogalski, E., Weintraub, S., Mesulam, M.M., Fleming, A., Coppola, G., Miller, B.L., Rubinsztein, D.C. (2017) A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction. Brain : a journal of neurology. 140(4):1128-1146
Keatinge, M., Bui, H., Menke, A., Chen, Y.C., Sokol, A.M., Bai, Q., Ellett, F., Da Costa, M., Burke, D., Gegg, M., Trollope, L., Payne, T., McTighe, A., Mortiboys, H., de Jager, S., Nuthhall, H., Kuo, M.S., Fleming, A., Schapira, A.H., Renshaw, S.A., Highley, J.R., Chacinska, A., Panula, P., Burton, E.A., O'Neill, M.J., Bandmann, O. (2015) Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Human molecular genetics. 24(23):6640-52
Jimenez-Sanchez, M., Lam, W., Hannus, M., Sönnichsen, B., Imarisio, S., Fleming, A., Tarditi, A., Menzies, F., Ed Dami, T., Xu, C., Gonzalez-Couto, E., Lazzeroni, G., Heitz, F., Diamanti, D., Massai, L., Satagopam, V.P., Marconi, G., Caramelli, C., Nencini, A., Andreini, M., Sardone, G.L., Caradonna, N.P., Porcari, V., Scali, C., Schneider, R., Pollio, G., O'Kane, C.J., Caricasole, A., Rubinsztein, D.C. (2015) siRNA screen identifies QPCT as a druggable target for Huntington's disease. Nature Chemical Biology. 11(5):347-54
Schiebler, M., Brown, K., Hegyi, K., Newton, S.M., Renna, M., Hepburn, L., Klapholz, C., Coulter, S., Obregón-Henao, A., Henao Tamayo, M., Basaraba, R., Kampmann, B., Henry, K.M., Burgon, J., Renshaw, S.A., Fleming, A., Kay, R.R., Anderson, K.E., Hawkins, P.T., Ordway, D.J., Rubinsztein, D.C., Floto, R.A. (2015) Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Molecular Medicine. 7(2):127-39
Moreau, K., Fleming, A., Imarisio, S., Lopez Ramirez, A., Mercer, J.L., Jimenez-Sanchez, M., Bento, C.F., Puri, C., Zavodszky, E., Siddiqi, F., Lavau, C.P., Betton, M., O'Kane, C.J., Wechsler, D.S., Rubinsztein, D.C. (2014) PICALM modulates autophagy activity and tau accumulation. Nature communications. 5:4998
Renna, M., Figueira-Bento, C., Fleming, A., Menzies, F.M., Siddiqi, F.H., Ravikumar, B., Puri, C., Garcia-Arencibia, M., Sadiq, O., Corrochano, S., Carter, S., Brown, S.D., Acevedo-Arozena, A., and Rubinsztein, D.C. (2013) IGF-1 Receptor Antagonism Inhibits Autophagy. Human molecular genetics. 22(22):4528-44
Fleming, A., Diekmann, H., and Goldsmith, P. (2013) Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. PLoS One. 8(10):e77548
Fleming, A., and Rubinsztein, D.C. (2011) Zebrafish as a model to understand autophagy and its role in neurological disease. Biochimica et biophysica acta. Molecular basis of disease. 1812(4):520-526
Buckley, C.E., Marguerie, A., Roach, A.G., Goldsmith, P., Fleming, A., Alderton, W.K., and Franklin, R.J. (2010) Drug reprofiling using zebrafish identifies novel compounds with potential pro-myelination effects. Neuropharmacology. 59(3):149-159
Underwood, B.R., Imarisio, S., Fleming, A., Rose, C., Krishna, G., Heard, P., Quick, M., Korolchuk, V.I., Renna, M., Sarkar, S., García-Arencibia, M., O'Kane, C.J., Murphy, M.P., and Rubinsztein, D.C. (2010) Antioxidants Can Inhibit Basal Autophagy and Enhance Neurodegeneration in Models of Polyglutamine Disease. Human molecular genetics. 19(17):3413-3429
Alderton, W., Berghmans, S., Butler, P., Chassaing, H., Fleming, A., Golder, Z., Richards, F., and Gardner, I. (2010) Accumulation and metabolism of drugs and CYP probe substrates in zebrafish larvae. Xenobiotica; the fate of foreign compounds in biological systems. 40(8):547-557
Fleming, A., Jankowski, J., and Goldsmith, P. (2010) In vivo analysis of gut function and disease changes in a zebrafish larvae model of inflammatory bowel disease: A feasibility study. Inflammatory bowel diseases. 16(7):1162-1172
Diekmann, H., Anichtchik, O., Fleming, A., Futter, M., Goldsmith, P., Roach, A., and Rubinsztein, D.C. (2009) Decreased BDNF levels are a major contributor to the embryonic phenotype of huntingtin knockdown zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(5):1343-1349
Berghmans, S., Barros, T., Golder, Z., Gardner, I., Butler, P., Hill, A., Fleming, A., Alderton, W., and Roach, A. (2008) Zebrafish: The future of in vivo safety pharmacology screening. Journal of Pharmacological and Toxicological Methods. 58(2):177-178
Anichtchik, O., Diekmann, H., Fleming, A., Roach, A., Goldsmith, P., and Rubinsztein, D.C. (2008) Loss of PINK1 function affects development and results in neurodegeneration in zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 28(33):8199-8207
Berghmans, S., Butler, P., Goldsmith, P., Waldron, G., Gardner, I., Golder, Z., Richards, F.M., Kimber, G., Roach, A., Alderton, W., and Fleming, A. (2008) Zebrafish based assays for the assessment of cardiac, visual and gut function - potential safety screens for early drug discovery. Journal of Pharmacological and Toxicological Methods. 58(1):59-68
Williams, A., Sarkar, S., Cuddon, P., Ttofi, E.K., Saiki, S., Siddiqi, F.H., Jahreiss, L., Fleming, A., Pask, D., Goldsmith, P., O'Kane, C.J., Floto, R.A., and Rubinsztein, D.C. (2008) Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nature Chemical Biology. 4(5):295-305
Best, J.D., Berghmans, S., Hunt, J.J., Clarke, S.C., Fleming, A., Goldsmith, P., and Roach, A.G. (2008) Non-Associative Learning in Larval Zebrafish. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 33(5):1206-1215
Fleming, A. (2007) Zebrafish as an alternative model organism for disease modelling and drug discovery: implications for the 3Rs. NC3Rs. 10(1):1-7
Barrett, R., Chappell, C., Quick, M., and Fleming, A. (2006) A rapid, high content, in vivo model of glucocorticoid-induced osteoporosis. Biotechnology Journal. 1(6):651-655
Fleming, A., Sato, M., and Goldsmith, P. (2005) High-Throughput In Vivo Screening for Bone Anabolic Compounds with Zebrafish. Journal of Biomolecular Screening. 10(8):823-831
Fleming, A., Keynes, R., and Tannahill, D. (2004) A central role for the notochord in vertebral patterning. Development (Cambridge, England). 131(4):873-880
Fleming, A., Keynes, R.J., and Tannahill, D. (2001) The role of the notochord in vertebral column formation. Journal of anatomy. 199(1-2):177-180

Anderson C.N., Ohta K., Quick M.M., Fleming A., Keynes R. and Tannahill D. (2003). Molecular analysis of axon repulsion by the notochord. Development. 130(6):1123-33.

Fleming, A. (2001). The role of folate in the prevention of neural tube defects: human and animal studies. Nutrition Reviews 59(8 Pt 2):S13-20; discussion S21-3.

Fleming, A. and Copp, A. J. (2000). A genetic risk factor for mouse neural tube defects: defining the embryonic basis. Human Molecular Genetics 9:575-581.

Fleming, A. and Copp, A. J. (1998). Embryonic folate metabolism and mouse neural tube defects. Science 280: 2107-2109.

Fleming, A., Gerrelli, D., Greene, N.D.E., and Copp, A.J. (1997). Mechanisms of normal and abnormal neurulation: evidence from embryo culture studies. International Journal of Developmental Biology 41: 199-212.