Antony Galione

Extraordinary Lecturer in Biochemical Pharmacology; Professor of Pharmacology

Medicine

MA PhD Camb, MA Oxf

antony.galione@pharm.ox.ac.uk

Antony Galione holds the Statutory Professorship of Pharmacology in the University and was the Head of the Department of Pharmacology from 2006-2015. He was Tutorial Fellow in Biochemical Pharmacology from 1998 2006, and is now an extraordinary lecturer in the subject.

Antony was educated at Felsted School where he was interested in classics and sciences. He eventually decided to study sciences at A level where he developed his interests in cell and molecular biology and biophysics. He went up to Trinity College Cambridge to read Natural Sciences with the ambition of becoming a protein crystallographer. However, in his first year he became fascinated by his lectures in physiology and in particular the effects of drugs and toxins on living systems, and was greatly influenced by his cell biology supervisor, Michael Berridge’s supervisions on cell regulation by calcium and cyclic AMP. He did his Part 2 in Pharmacology while also attending lectures in Egyptology. He stayed on in Cambridge to do a PhD on calcium signalling with Sir Michael Berridge in the Department of Zoology, working on how flies spit (the regulation of salivary glands by the hormones and second messengers).
After a brief spell at UCL working on mammalian fertilization he was a Harkness Fellow at The Johns Hopkins University working on calcium gradients and embryogenesis of frogs.
He came to Oxford in 1991 as a Beit Memorial Fellow where he worked on a new way of regulating intracellular calcium, the second messenger cyclic ADP-ribose, working on sea urchin eggs and mammalian cells
He was successively a Wellcome Trust Career Development Fellow and a Senior Fellow in Basic Biomedical Sciences
He was the Hayward Junior Research Fellow at Oriel College from 1992-1995, and Staines Medical Fellow at Exeter College from 1995-1998 before being elected to a Tutorial Fellowship and University Lecturership in Biochemical Pharmacology in 1998. He was also lectuer in Medicine at St Hilda’s College and in Biochemistry at St Catherine’s College.
He was appointed to the Statutory Chair of Pharmacology in 2006 and became Head of Department in 2006.
He was elected a Fellow of the Academy of Medical Sciences in 2010, and a Fellow of The Royal Society in 2016.

Antony lives in a tiny village in the Cotswolds with his wife, two Jack Russell terriers and two horses.

Antony enjoys listening to the choir practice from his rooms in New Buildings whilst being educated by students during tutorials

Teaching

Physiology and Pharmacology for 1st year preclinical medical students

Cells and Body for 1st year Biomedical Sciences students
Neuropharmacology and Applied Physiology/Pharmacology for 2nd year preclinical medical students
Cell signalling for 2nd year Biochemistry Students
Cell (especially Calcium) signalling at the Final Honours School level (3rd year) in Medical/Biomedical Sciences

Research Interests

Antony Galione is a pharmacologist whose work has helped discover new calcium signalling pathways. He established the concept of multiple calcium mobilizing messengers which link cell surface stimuli to release of internal calcium stores, and identified their target channels and organelles. This has enhanced our understanding of how calcium as a ubiquitous cellular regulator may control a myriad of cellular processes with precision.

He showed that cyclic ADP-ribose regulates calcium-induced calcium release and globalization of calcium signals, and that NAADP is a ubiquitous trigger for initiating and coordinating calcium signals, often involving communication between organelles at contact sites.

By developing novel pharmacological, molecular and physiological approaches, he has demonstrated that these messengers and their targets regulate many fundamental pathophysiological cellular processes as diverse as Ebola infection, fertilization and embryo development, cardiac contractility, T cell activation and neuronal excitability. The discovery of lysosomes as calcium stores mobilized by NAADP has identified an entirely new signalling role for these organelles in health and disease.

Selected publications

Galione, A., Lee, H.C., and Busa, W.B. (1991) Ca2+-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science 253, 1143-1146.
Galione, A., McDougall, A., Busa, W.B., Willmott, N., Gillot, I., and Whitaker, M. (1993) Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs. Science 261, 348-352.
Galione, A., White, A., Willmott, N., Turner, M., Potter, B.V., and Watson, S.P. (1993) cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature 365, 456-459.
Cancela, J.M., Churchill, G.C., and Galione, A. (1999). Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature 398, 74-76.
Churchill, G. C. and Galione, A. (2000) Spatial control of Ca2+ signaling by nicotinic acid adenine dinucleotide phosphate diffusion and gradients. J. Biol. Chem. 275, 38687-38692.
Churchill, G. C. and Galione, A. (2001) NAADP induces Ca2+ oscillations via a two-pool mechanism by priming IP3- and cADPR-sensitive Ca2+ stores. EMBO. J. 20, 2666-2671.
Churchill, G.C., Okada, Y., Thomas, J.M., Genazzani, A.A., Patel, S., and Galione, A. (2002) NAADP mobilizes Ca2+ from reserve granules, lysosome-related organelles, in sea urchin eggs. Cell 111, 703-708.
Churchill, G. C., O'Neill, J. S., Masgrau, R., Patel, S., Thomas, J. M., Genazzani, A. A., and Galione, A. (2003) Sperm deliver a new second messenger: NAADP. Curr. Biol. 13, 125-128.
Yamasaki, M., Masgrau, R., Morgan, A.J., Churchill, G.C., Patel, S., Ashcroft, S.J., and Galione, A. (2004) Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells. J. Biol. Chem. 279, 7234-7240.
Yamasaki, M., Thomas, J.M., Churchill, G.C., Garnham, C., Lewis, A.M., Cancela, J.M., Patel, S., and Galione, A. (2005) Role of NAADP and cADPR in the induction and maintenance of agonist-evoked Ca2+ spiking in mouse pancreatic acinar cells. Curr. Biol. 15, 874-878.
Davis, L.C., Morgan, A.J., Ruas, M., Wong, J.L., Graeff, R.M., Poustka, A.J., Lee, H.C., Wessel, G.M., Parrington, J., and Galione, A. (2008) Ca2+ signaling occurs via second messenger release from intraorganelle synthesis sites. Curr. Biol. 18, 1612-1618.
Lloyd-Evans, E., Morgan, A. J., He, X., Smith, D. A., Elliot-Smith, E., Sillence, D. J., Churchill, G. C., Schuchman, E. H., Galione, A., and Platt, F. M. (2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat. Med. 14, 1247-1255.
Calcraft, P.J., Ruas, M., Pan, Z., Cheng, X., Arredouani, A., Hao, X., Tang, J., Rietdorf, K., Teboul, L., Chuang, K.T., Lin, P., Xiao, R., Wang, C., Zhu, Y., Lin, Y., Wyatt, C.N., Parrington, J., Ma, J., Evans, A.M., Galione, A., and Zhu, M.X. (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459, 596-600.
Ruas, M., Rietdorf, K., Arredouani, A., Davis, L.C., Lloyd-Evans, E., Koegel, H., Funnell, T.M., Morgan, A.J., Ward, J.A., Watanabe, K., Cheng, X., Churchill, G.C., Zhu, M.X., Platt, F.M., Wessel, G.M., Parrington, J., & Galione, A. (2010) Purified TPC isoforms form NAADP receptors with distinct roles for Ca2+ signaling and endolysosomal trafficking. Curr. Biol. 20, 403-409.
Pitt, S.J., Funnell, T., Sitsapesan, M., Venturi, E., Rietdorf, K., Ruas, M., Ganesan, A., Gosain, R., Churchill, G.C., Zhu, M.X., Parrington, J., Galione, A., & Sitsapesan, R. (2010) TPC2 is a novel NAADP-sensitive Ca2+-release channel, operating as a dual sensor of luminal pH and Ca2+. J. Biol. Chem. 265, 35039-35046.
Davis, L.C., Morgan, A.J., Chen, J-L, Snead,C.M., Bloor-Young, D., Shenderov, E., Stanton-Humphreys, M.N. Conway, S.J., Churchill, G.C., Parrington, J., Cerundolo, V. and Galione, A. (2012) NAADP activates two-pore channels on T-cell cytolytic granules to stimulate exocytosis and killing. Curr. Biol. 22, 2331-2337.
Morgan, A.J., Davis, L.C., Wagner, S.K., Lewis, A.M., Parrington, J., Churchill, G.C., and Galione, A. (2013). Bidirectional Ca2+ signaling occurs between the endoplasmic reticulum and acidic organelles. J. Cell Biol. 200, 789-805.
Favia, A., Desideri, M., Gambara, G., D'Alessio, A., Ruas, M., Esposito, B., Del Bufalo, D., Parrington, J., Ziparo, E., Palombi, F., Galione, A., and Filippini, A. (2014) VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling. Proc. Natl. Acad. Sci. U.S.A. 111, 4706-4715
Ruas, M., Davis, L. C., Chen, C. C., Morgan, A. J., Chuang, K. T., Walseth, T. F., Grimm, C., Garnham, C., Powell, T., Platt, N., Platt, F. M., Biel, M., Wahl-Schott, C., Parrington, J., and Galione, A. (2015) Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells. EMBO J. 34, 1743-1758.
Arredouani, A., Ruas, M., Collins, S. C., Parkesh, R., Clough, F., Pillinger, T., Coltart, G., Rietdorf, K., Royle, A., Johnson, P., Braun, M., Zhang, Q., Sones, W., Shimomura, K., Morgan, A. J., Lewis, A. M., Chuang, K. T., Tunn, R., Gadea, J., Teboul, L., Heister, P. M., Tynan, P. W., Bellomo, E. A., Rutter, G. A., Rorsman, P., Churchill, G. C., Parrington, J., and Galione, A. (2015) NAADP and endolysosomal two-pore channels modulate membrane excitability and stimulus-secretion coupling in mouse pancreatic beta cells. J. Biol. Chem. 290, 21376-21392.

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