Professor Antony Galione FMedSci

Chair of Pharmacology & Head of Department
Regulation of intracellular channels Calcium-mobilising second messengers, Cyclic ADP-ribose and NAADP as second messengers, Organization of intracellular Ca2+ signals, Molecular characterization of novel calcium release channels, Molecular signaling at fertilization, Stimulus-secretion coupling in exocrine and endocrine pancreas Excitation-contraction coupling in striated and smooth muscle Role of acidic calcium stores in calcium signaling

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College	New College

Research summary

Prof Antony Galione

Professor Galione was educated at Trinity College, Cambridge and received a BA in Natural Sciences (Part 2 Pharmacology) in 1985. Remaining at Cambridge University he obtained his PhD in 1989 having worked on the role of calcium oscillations in cell activation in Michael Berridge's laboratory.

After a short spell at UCL working on mammalian fertilisation with Michael Whitaker, he went to Johns Hopkins University as a Harkness Fellow studying the role of calcium signals in early development. Returning to the UK in 1991, he joined the Department of Pharmacology. He has been successively a Beit Memorial Fellow, Wellcome Trust Career Development Fellow and Wellcome Trust Senior Fellow in Basic Biomedical Research.

He was also Hayward Junior Research Fellow at Oriel College and Staines Medical Fellow at Exeter College. He was elected to a Tutorial Fellowship at New College in 1998 in conjunction with a proleptic University appointment. He was appointed to a titular Professor of Pharmacology in 2002, and in 2006 was elected to the Professorship of Pharmacology. Since joining the Department, Professor Galione's principal research interest has been the regulation of intracellular calcium signalling by cyclic ADP-ribose and NAADP, emerging intracellular messengers for calcium mobilisation. This work has led to the identification of new biochemical pathways controlling calcium signals that regulate processes as diverse as fertilisation, secretion, contractility and neuronal excitability using a multidisciplinary approach based on confocal microscopy, video-imaging, electrophysiology, flash photolysis, microsomal calcium flux measurements and molecular and biochemical techniques. A new focus of his work is the study of the physiological roles of the family of the endolysosomal two-pore channels (TPCs) as the intracellular targets for NAADP and their role in calcium signalling.

CICR amplification and globalization

Three distinct modes of NAADP mediated Ca2+ signalling
A. NAADP is a local trigger mechanism for detonating global Ca2+ induced Ca2+ release (CICR) responses from the ER. NAADP acts at TPCs (probable dimers) on acidic Ca2+ stores to evoke a local Ca2+ release. Depending on the juxtaposition to ER Ca2+ release channels, this may trigger a larger, globalized Ca2+ release dependent on endogenous IP3 and cADPR presence for IP3 R or RyR recruitment, repectively.
B. Local Ca2+ release by NAADP from acidic stores positioned under the plasma membrane may regulate membrane excitability (excitable cells) or ion fluxes (non‐excitable cells) by modulating Ca2+ activated plasma membrane channels.
C. NAADP regulates local cytoplasmic Ca2+ / pH and luminal Ca2+ / pH in endolysosomal compartments that may regulate vesicular fusion of late endosomes/lysosomes important for organelle biogenesis and trafficking.

Professor Galione is an Editor of the Biochemical Journal, a member of the Editorial Board of Zygote, and Calcium Binding Proteins. He received the 2001 Novartis Prize of the British Pharmacological Society for his scientific contributions to Pharmacology and was elected to the Academy of Medical Sciences in 2010.

Biography

2012

NAADP activates two-pore channels on T cell cytolytic granules to stimulate exocytosis and killing.: Davis, LC, Morgan, AJ, Chen, J, Snead, CM, Bloor-Young, D, Shenderov, E, Stanton-Humphreys, MN, Conway, SJ, Churchill, GC, Parrington, J, Cerundolo, V, and Galione, A
Curr Biol, 22(24):2331-7.
Photoaffinity labeling of high affinity nicotinic acid adenine dinucleotide phosphate (NAADP)-binding proteins in sea urchin egg.: Walseth, TF, Lin-Moshier, Y, Jain, P, Ruas, M, Parrington, J, Galione, A, Marchant, JS, and Slama, JT
J Biol Chem, 287(4):2308-15.
The luminal Ca(2+) chelator, TPEN, inhibits NAADP-induced Ca(2+) release.: Morgan, AJ, Parrington, J, and Galione, A
Cell Calcium, 52(6):481-7.
ß-Adrenergic receptor signaling increases NAADP and cADPR levels in the heart.: Lewis, AM, Aley, PK, Roomi, A, Thomas, JM, Masgrau, R, Garnham, C, Shipman, K, Paramore, C, Bloor-Young, D, Sanders, LEL, Terrar, DA, Galione, A, and Churchill, GC
Biochem Biophys Res Commun, 427(2):326-9.

2011

Development of inositol-based antagonists for the D-myo-inositol 1,4,5-trisphosphate receptor.: Keddie, NS, Ye, Y, Aslam, T, Luyten, T, Bello, D, Garnham, C, Bultynck, G, Galione, A, and Conway, SJ
Chem Commun (Camb), 47(1):242-4.
Loss of activity mutations in phospholipase C zeta (PLCzeta) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes.: Kashir, J, Jones, C, Lee, HC, Rietdorf, K, Nikiforaki, D, Durrans, C, Ruas, M, Tee, ST, Heindryckx, B, Galione, A, De Sutter, P, Fissore, RA, Parrington, J, and Coward, K
Hum Reprod, 26(12):3372-87.
Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease.: Morgan, AJ, Platt, FM, Lloyd-Evans, E, and Galione, A
Biochem J, 439(3):349-74.
NAADP influences excitation-contraction coupling by releasing calcium from lysosomes in atrial myocytes.: Collins, TP, Bayliss, R, Churchill, GC, Galione, A, and Terrar, DA
Cell Calcium, 50(5):449-58.
NAADP links histamine H1 receptors to secretion of von Willebrand factor in human endothelial cells.: Esposito, B, Gambara, G, Lewis, AM, Palombi, F, D'Alessio, A, Taylor, LX, Genazzani, AA, Ziparo, E, Galione, A, Churchill, GC, and Filippini, A
Blood, 117(18):4968-77.
NAADP receptors.: Galione, A
Cold Spring Harb Perspect Biol, 3(1):a004036.
Synthesis of cyclic adenosine 5'-diphosphate ribose analogues: a C2'endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptor.: Moreau, C, Ashamu, GA, Bailey, VC, Galione, A, Guse, AH, and Potter, BVL
Org Biomol Chem, 9(1):278-90.
Two-pore channels form homo- and heterodimers.: Rietdorf, K, Funnell, TM, Ruas, M, Heinemann, J, Parrington, J, and Galione, A
J Biol Chem, 286(43):37058-62.

2010

Acidic NAADP-sensitive calcium stores in the endothelium: agonist-specific recruitment and role in regulating blood pressure.: Brailoiu, GC, Gurzu, B, Gao, X, Parkesh, R, Aley, PK, Trifa, DI, Galione, A, Dun, NJ, Madesh, M, Patel, S, Churchill, GC, and Brailoiu, E
J Biol Chem, 285(48):37133-7.
Ca2+ release from the endoplasmic reticulum of NY-ESO-1-specific T cells is modulated by the affinity of TCR and by the use of the CD8 coreceptor.: Chen, J, Morgan, AJ, Stewart-Jones, G, Shepherd, D, Bossi, G, Wooldridge, L, Hutchinson, SL, Sewell, AK, Griffiths, GM, van der Merwe, PA, Jones, EY, Galione, A, and Cerundolo, V
J Immunol, 184(4):1829-39.
NAADP as an intracellular messenger regulating lysosomal calcium-release channels.: Galione, A, Morgan, AJ, Arredouani, A, Davis, LC, Rietdorf, K, Ruas, M, and Parrington, J
Biochem Soc Trans, 38(6):1424-31.
Nicotinic acid adenine dinucleotide phosphate regulates skeletal muscle differentiation via action at two-pore channels.: Aley, PK, Mikolajczyk, AM, Munz, B, Churchill, GC, Galione, A, and Berger, F
Proc Natl Acad Sci U S A, 107(46):19927-32.
Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking.: Ruas, M, Rietdorf, K, Arredouani, A, Davis, LC, Lloyd-Evans, E, Koegel, H, Funnell, TM, Morgan, AJ, Ward, JA, Watanabe, K, Cheng, X, Churchill, GC, Zhu, MX, Platt, FM, Wessel, GM, Parrington, J, and Galione, A
Curr Biol, 20(8):703-9.
TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.: Pitt, SJ, Funnell, TM, Sitsapesan, M, Venturi, E, Rietdorf, K, Ruas, M, Ganesan, A, Gosain, R, Churchill, GC, Zhu, MX, Parrington, J, Galione, A, and Sitsapesan, R
J Biol Chem, 285(45):35039-46.
TPC2 proteins mediate nicotinic acid adenine dinucleotide phosphate (NAADP)- and agonist-evoked contractions of smooth muscle.: Tugba Durlu-Kandilci, N, Ruas, M, Chuang, K, Brading, A, Parrington, J, and Galione, A
J Biol Chem, 285(32):24925-32.
The calcium-mobilizing messenger nicotinic acid adenine dinucleotide phosphate participates in sperm activation by mediating the acrosome reaction.: Vasudevan, SR, Lewis, AM, Chan, JW, Machin, CL, Sinha, D, Galione, A, and Churchill, GC
J Biol Chem, 285(24):18262-9.
The ecto-enzyme CD38 is a nicotinic acid adenine dinucleotide phosphate (NAADP) synthase that couples receptor activation to Ca2+ mobilization from lysosomes in pancreatic acinar cells.: Cosker, F, Cheviron, N, Yamasaki, M, Menteyne, A, Lund, FE, Moutin, M, Galione, A, and Cancela, J
J Biol Chem, 285(49):38251-9.
Two-pore channels for integrative Ca signaling.: Zhu, MX, Evans, AM, Ma, J, Parrington, J, and Galione, A
Commun Integr Biol, 3(1):12-7.