Dr Grant Churchill
Determinations of cyclic ADP-ribose and NAADP levels. Endogenous synthesis and metabolism of NAADP. Signal transduction pathway underlying NAADP production. Spatial and temporal control of calcium increases by NAADP. Physiological roles of NAADP and lysosome-related calcium-storing organelles. Development of caged and cellpermeant messengers.
Dr Grant Churchill
Dr Churchill obtained a Bachelors degree in Agriculture and a Masters degree in Crop Science from the University of Saskatchewan. His Masters research on structure-activity relationships for the plant hormone abscisic acid generated his interest in small molecule synthesis and how chemistry can be used to probe biological function. He then switched fields and obtained a PhD in Biochemistry, Biophysics and Molecular Biology from the University of Minnesota.
His PhD research focused on calcium regulation in the lens of the eye. Then, with combined interests in chemistry and calcium signalling, he came to Oxford to join Professor Antony Galione’s group as a postdoctoral research associate. Subsequently, he was awarded the Todd-Bird Junior Research Fellowship at New College, Oxford. His investigations at Oxford into pyridinerelated compounds that release calcium from internal stores have been, and continue to be, the focus of his research. Dr Churchill utilizes the synthesis of small molecules to provide unique tools to investigate biological questions. Not only are these compounds useful for understanding physiology but also may ultimately provide new lead compounds for drugs.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.