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Trevor J. Shuttleworth, Ph.D.

Trevor J. Shuttleworth, Ph.D.

About Me

Faculty Appointments

Professor Emeritus - Department of Pharmacology and Physiology (SMD)

Credentials

Post-doctoral Training & Residency

SRC Research Associate, Department of Biological Sciences, University of Lancaster, England 1972 - 1974

Education

PhD | New Zealand-Univ of Otago. Zoology/Comp. Physiology. 1972

BS | UK-Univ of London. Zoology. 1968

Awards

Chair and Organizer, Satellite Symposium on "Orai Channels--New Insights, New Ideas". 2012

Plenary Speaker, Ion Channel Signaling Mechanisms: from Basic Science to Clinical Applications. 2011 - 2011

Session Chair - Salivary Glands and Saliva. 2003

Session Chair - 5th UK Calcium Signalling Conference, Liverpool, England. 2003

Session Chair - Professor Sir Michael Berridge Retirement Conference, Cambridge, England. 2003

Session Chair - International Workshop on "Experimental and Theoretical Calcium Dynamics" Max-Planck institute for the Physics of Complex Systems, Dresden, Germany 2000

Session Chair - Experimental Biology 1993 (FASEB) meeting, New Orleans 1993

Session Chair - Joint Meeting of the APS, ASZ, CSZ and SEB, Cambridge, England 1992

Session Chair - International Symposium on "Mechanisms of Systemic Regulation in Lower Vertebrates", Göttingen, Germany 1990

Session Chair - Society for Experimental Biology Conference, York, U.K. 1987

Session Chair - IUPS International Congress, Vancouver, Canada 1986

Session Chair - IUPS Satellite Symposium on "Membrane Transport and Control: Comparative Mechanisms", Banff, Canada 1986

Session Chair - Society for Experimental Biology Conference, Bangor, U.K. 1985

Session Chair - Society for Experimental Biology Conference, Cardiff, U.K. 1984

Session Chair - Seminar Series Symposium of the Society for Experimental Biology, Durham, U.K. 1981

Session Chair - Society for Experimental Biology Conference, Lancaster, U.K. 1979

Science Research Council Fellowship (U.K.), University of Lancaster, England 1972 - 1974

University of Otago Teaching Fellowship, University of Otago, New Zealand 1969 - 1972

Research

The cellular actions of many neurotransmitters and hormones are dependent on receptor-activated increases in intracellular calcium concentrations in their target cells. In various secretory and other "non-excitable" cells, the physiologically relevant signals often take the form of a series of Ca2+ ...
The cellular actions of many neurotransmitters and hormones are dependent on receptor-activated increases in intracellular calcium concentrations in their target cells. In various secretory and other "non-excitable" cells, the physiologically relevant signals often take the form of a series of Ca2+ oscillations, and many critical cellular responses are tuned to respond to the specific frequency of such oscillations. A key factor in sustaining these signals and determining their frequency, is the receptor-activated entry of Ca2+ from the extracellular medium. Our research concerns the nature of the conductances responsible for this entry, and their specific roles in modulating the overall Ca2+ signal. Specifically, our recent research has focused on the ARC channel – a novel Ca2+ entry channel that is activated by the receptor-mediated generation of arachidonic acid, and which we first described a few years ago. Importantly, it is this channel that appears to play the major role in the entry of Ca2+ during the generation of the oscillatory Ca2+ signals in several cell types. We have recently characterized the key molecular components of this channel, revealing that it is a member of a new family of channels – the "Orai-based channels". This molecular characterization has opened up new opportunities for the analysis of its nature, mechanism of activation, and regulation. This, along with identifying how the Ca2+ entering via this channel acts to modulate the frequency of the agonist-induced Ca2+ oscillations, forms the major focus of our current research.

Techniques used include patch-clamp analysis of ion-channel activity, digital imaging, real-time confocal imaging, and photon-counting microfluorimetric measurements of intracellular Ca2+ concentrations in single cells, and biochemical and molecular studies of the proteins that form the channel and its regulators.

Publications

Journal Articles

Shuttleworth TJ

Cell calcium.. 2017 May 63 :40-42. Epub 11/04/2016.

Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2015 February 1593 (3):559-72. Epub 01/07/2015.

Duquette M, Nadler M, Okuhara D, Thompson J, Shuttleworth T, Lawler J

Matrix biology : journal of the International Society for Matrix Biology.. 2014 July 37 :15-24. Epub 05/16/2014.

How many Orai's does it take to make a CRAC channel?

Thompson, JL; Shuttleworth, TJ.

Nature Scientific Reports. 2013; 3: 1961.

Molecular basis of activation of the arachidonate-regulated ARC channel, a store-independent Orai channel, by plasma membrane STIM1

Thompson, JL; Shuttleworth, TJ.

The Journal of Physiology. 2013; 591: 3507-3523.

Exploring the unique features of the ARC channel, a store-independent Orai channel

Thompson, JL.; Shuttleworth, TJ.

Channels. 2013; 7: 364-373.

Thompson JL, Mignen O, Shuttleworth TJ

Current topics in membranes.. 2013 71 :125-48. Epub 1900 01 01.

Shuttleworth TJ

The Journal of physiology.. 2012 September 1590 (17):4155-6. Epub 1900 01 01.

Palk L, Sneyd J, Patterson K, Shuttleworth TJ, Yule DI, Maclaren O, Crampin EJ

Journal of theoretical biology.. 2012 July 21305 :45-53. Epub 04/14/2012.

Shuttleworth TJ

The Journal of physiology.. 2012 January 15590 (2):241-57. Epub 10/31/2011.

STIM and Orai proteins and the non-capacitative ARC channels

Shuttleworth, TJ.

Frontiers in Bioscience. 2012; 17: 847-860.

Thompson JL, Shuttleworth TJ

Channels.. 2012 6 (5):370-8. Epub 09/01/2012.

Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2011 November 1589 (Pt 21):5057-69. Epub 08/30/2011.

Palk L, Sneyd J, Shuttleworth TJ, Yule DI, Crampin EJ

Journal of theoretical biology.. 2010 October 21266 (4):625-40. Epub 06/25/2010.

Thompson JL, Mignen O, Shuttleworth TJ

Channels.. 2010 4 (5):398-410. Epub 09/01/2010.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2009 September 1587 (Pt 17):4181-97. Epub 07/21/2009.

Shuttleworth TJ

Cell calcium.. 2009 June 45 (6):602-10. Epub 03/17/2009.

Thompson JL, Mignen O, Shuttleworth TJ

The Journal of biological chemistry.. 2009 March 13284 (11):6620-6. Epub 12/15/2008.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2008 January 15586 (2):419-25. Epub 11/15/2007.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2008 January 1586 (1):185-95. Epub 11/08/2007.

Shuttleworth TJ, Thompson JL, Mignen O

Cell calcium.. 2007 August 42 (2):183-91. Epub 03/27/2007.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2007 March 15579 (Pt 3):703-15. Epub 12/07/2006.

A mathematical model of fluid secretion from a parotid acinar cell.

Gin,E.; Crampin,E.J.; Brown,D.A.; Shuttleworth,T.J.; Yule,D.I.; and Snyd,J.

J.Theoret.Biol. 2007; 248: 64-80.

Shuttleworth TJ, Thompson J, Munger RS, Wood CM

The Journal of experimental biology.. 2006 December 209 (Pt 23):4701-16. Epub 1900 01 01.

Mignen O, Brink C, Enfissi A, Nadkarni A, Shuttleworth TJ, Giovannucci DR, Capiod T

Journal of cell science.. 2005 December 1118 (Pt 23):5615-23. Epub 1900 01 01.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of physiology.. 2005 September 15567 (Pt 3):787-98. Epub 06/30/2005.

Mignen O, Thompson JL, Yule DI, Shuttleworth TJ

The Journal of physiology.. 2005 May 1564 (Pt 3):791-801. Epub 03/10/2005.

Melvin JE, Yule D, Shuttleworth T, Begenisich T

Annual review of physiology.. 2005 67 :445-69. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL, Mignen O

Physiology.. 2004 December 19 :355-61. Epub 1900 01 01.

Shuttleworth TJ

Science's STKE : signal transduction knowledge environment. 2004 July 202004 (243):pe40. Epub 07/20/2004.

Bruce JI, Giovannucci DR, Blinder G, Shuttleworth TJ, Yule DI

The Journal of biological chemistry.. 2004 March 26279 (13):12909-17. Epub 12/29/2003.

Yule DI, Sneyd J, Thompson JL, Tsaneva-Atanasova K, Shuttleworth TJ, Yule DI, Thompson JL, Shuttleworth TJ

Proceedings of the National Academy of Sciences of the United States of America.. 2004 February 3101 (5):1392-6. Epub 01/20/2004.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of biological chemistry.. 2003 October 10278 (41):40088-96. Epub 07/21/2003.

Shuttleworth TJ, Mignen O

Biochemical Society transactions.. 2003 October 31 (Pt 5):916-9. Epub 1900 01 01.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of biological chemistry.. 2003 March 21278 (12):10174-81. Epub 01/09/2003.

Bruce JI, Yule DI, Shuttleworth TJ

The Journal of biological chemistry.. 2002 December 13277 (50):48172-81. Epub 10/03/2002.

Giovannucci DR, Bruce JI, Straub SV, Arreola J, Sneyd J, Shuttleworth TJ, Yule DI

The Journal of physiology.. 2002 April 15540 (Pt 2):469-84. Epub 1900 01 01.

Bruce JI, Shuttleworth TJ, Giovannucci DR, Yule DI

The Journal of biological chemistry.. 2002 January 11277 (2):1340-8. Epub 11/01/2001.

Mignen O, Thompson JL, Shuttleworth TJ

The Journal of biological chemistry.. 2001 September 21276 (38):35676-83. Epub 07/24/2001.

Mignen O, Shuttleworth TJ

The Journal of biological chemistry.. 2001 June 15276 (24):21365-74. Epub 04/02/2001.

Mignen O, Shuttleworth TJ

The Journal of biological chemistry.. 2000 March 31275 (13):9114-9. Epub 1900 01 01.

Osterhout JL, Shuttleworth TJ

The Journal of biological chemistry.. 2000 March 17275 (11):8248-54. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Journal of biological chemistry.. 1999 October 29274 (44):31174-8. Epub 1900 01 01.

Shuttleworth TJ, Hildebrandt JP

The Journal of experimental zoology.. 1999 June 1283 (7):689-701. Epub 1900 01 01.

Shuttleworth TJ

Cell calcium.. 1999 March 25 (3):237-46. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Journal of biological chemistry.. 1998 December 4273 (49):32636-43. Epub 1900 01 01.

Shuttleworth TJ

The Journal of experimental biology.. 1997 January 200 (Pt 2):303-14. Epub 1900 01 01.

Martin SC, Shuttleworth TJ

Annals of the New York Academy of Sciences.. 1996 December 26805 :133-47; discussion 147-8. Epub 1900 01 01.

Wu JV, Shuttleworth TJ, Stampe P

The Journal of membrane biology.. 1996 December 154 (3):275-82. Epub 1900 01 01.

Shuttleworth TJ

The Journal of biological chemistry.. 1996 September 6271 (36):21720-5. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Biochemical journal.. 1996 June 15316 ( Pt 3) (Pt 3):819-24. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Biochemical journal.. 1996 February 1313 ( Pt 3) (Pt 3):815-9. Epub 1900 01 01.

Shuttleworth TJ

Cell calcium.. 1995 June 17 (6):393-8. Epub 1900 01 01.

Martin SC, Shuttleworth TJ

British journal of pharmacology.. 1995 May 115 (2):321-9. Epub 1900 01 01.

Martin SC, Shuttleworth TJ

FEBS letters.. 1994 September 19352 (1):32-6. Epub 1900 01 01.

Martin SC, Shuttleworth TJ

Regulatory peptides.. 1994 August 452 (3):205-14. Epub 1900 01 01.

Martin SC, Thompson J, Shuttleworth TJ

The American journal of physiology.. 1994 July 267 (1 Pt 1):C255-65. Epub 1900 01 01.

Shuttleworth TJ

Cell calcium.. 1994 June 15 (6):457-66. Epub 1900 01 01.

Hildebrandt JP, Shuttleworth TJ

The American journal of physiology.. 1994 March 266 (3 Pt 2):R674-81. Epub 1900 01 01.

Martin SC, Shuttleworth TJ

Pflu?gers Archiv : European journal of physiology.. 1994 February 426 (3-4):231-8. Epub 1900 01 01.

Hildebrandt JP, Shuttleworth TJ

The Journal of membrane biology.. 1993 April 133 (2):183-90. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

Cell calcium.. 1992 October 13 (9):541-51. Epub 1900 01 01.

Hildebrandt JP, Shuttleworth TJ

The Biochemical journal.. 1992 March 15282 ( Pt 3) (Pt 3):703-10. Epub 1900 01 01.

Shuttleworth TJ

The Journal of biological chemistry.. 1992 February 25267 (6):3573-6. Epub 1900 01 01.

Shuttleworth TJ, Wood CM

The American journal of physiology.. 1992 January 262 (1 Pt 1):C221-8. Epub 1900 01 01.

Hildebrandt JP, Shuttleworth TJ

The American journal of physiology.. 1991 August 261 (2 Pt 1):C210-7. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Journal of biological chemistry.. 1991 January 25266 (3):1410-4. Epub 1900 01 01.

Shuttleworth TJ

The Biochemical journal.. 1990 July 15269 (2):417-22. Epub 1900 01 01.

Shuttleworth TJ

The Biochemical journal.. 1990 March 15266 (3):719-26. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The American journal of physiology.. 1989 November 257 (5 Pt 1):C1020-9. Epub 1900 01 01.

Overview of epithelial ion-transport mechanisms.

Shuttleworth, T.J.

Can. J. Zool. 1989; 67: 3032-3038.

Dimaline R, Young J, Thwaites DT, Lee CM, Shuttleworth TJ, Thorndyke MC

Biochimica et biophysica acta.. 1987 August 19930 (1):97-100. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL, Dantzler WH

The American journal of physiology.. 1987 July 253 (1 Pt 2):R83-90. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The American journal of physiology.. 1987 February 252 (2 Pt 2):R428-32. Epub 1900 01 01.

Stagg RM, Shuttleworth TJ

Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology.. 1987 157 (4):429-34. Epub 1900 01 01.

Davis MS, Shuttleworth TJ

The American journal of physiology.. 1986 December 251 (6 Pt 2):R1064-70. Epub 1900 01 01.

Shuttleworth TJ, Thompson JL

The Journal of experimental biology.. 1986 September 125 :373-84. Epub 1900 01 01.

Surfactant effects on adrenergic responses in the gills of the flounder (Platichthys flesus L.)

Stagg, R.M.; Shuttleworth, T.J.

J. Comp. Physiol. 1986; 156: 727-733.

Peptidergic and adrenergic regulation of electrogenic ion transport in isolated gills of the flounder (Platichthys flesus L.)

Davis, M.S.; Shuttleworth, T.J.

J. Comp. Physiol. 1985; : 471-478.

Distribution of intracellular sodium, potassium and chloride in Arenicola marina (L.) equilibrated to diluted sea water.

Freeman, R.F.H.; Shuttleworth, T.J.

J. Mar. Biol. Ass. U.K. 1985; 65: 395-413.

Davis MS, Shuttleworth TJ

Peptides.. 1985 6 Suppl 3 :379-82. Epub 1900 01 01.

Thorndyke MC, Shuttleworth TJ

Peptides.. 1985 6 Suppl 3 :369-72. Epub 1900 01 01.

Shuttleworth TJ, Thorndyke MC

Science.. 1984 July 20225 (4659):319-21. Epub 1900 01 01.

Shuttleworth TJ, Goldstein L

The Journal of experimental zoology.. 1984 July 231 (1):39-44. Epub 1900 01 01.

Stagg RM, Shuttleworth TJ

The American journal of physiology.. 1984 February 246 (2 Pt 2):R211-20. Epub 1900 01 01.

Shuttleworth TJ

The American journal of physiology.. 1983 December 245 (6):R894-900. Epub 1900 01 01.

Shuttleworth TJ

The Journal of experimental biology.. 1983 March 103 :193-204. Epub 1900 01 01.

Shuttleworth TJ

The Journal of experimental zoology.. 1982 June 10221 (2):255-8. Epub 1900 01 01.

Na, K ATPase, ouabain binding and ouabain-sensitive oxygen consumption in gills from Platichthys flesus adapted to seawater and freshwater.

Stagg, R.M.; Shuttleworth, T.J.

J. Comp. Physiol. 1982; 147: 93-99.

The accumulation of copper in Platichthys flesus L. and its effects on plasma electrolyte concentrations.

Stagg, R.M.; Shuttleworth, T.J.

J. Fish Biol. 1982; : 491-500.

The mechanism of cyclic AMP stimulation of secretion in the dogfish rectal gland.

Shuttleworth, T.J.; Thompson, J.L.

J. Comp. Physiol. 1980; : 209-216.

Oxygen consumption in the rectal gland of the dogfish Scyliorhinus canicula and the effects of cyclic AMP.

Shuttleworth, T.J.; Thompson, J.L.

J. Comp. Physiol. 1980; 136: 39-43.

Cyclic AMP and ouabain-binding sites in the rectal gland of the dogfish Scyliorhinus canicula.

Shuttleworth, T.J.; Thompson, J.L.

J. Exp. Zool. 1978; 206: 297-302.

The effect of adrenaline on potentials in the isolated gills of the flounder (Platichthys flesus L.).

Shuttleworth, T.J.

J. Comp. Physiol. 1978; 124: 129-136.

Distribution of intracellular solutes in Arenicola marina (Polychaeta) equilibrated to diluted sea water.

Freeman, R.F.H.; Shuttleworth, T.J.

J. Mar. Biol. Ass. U.K. 1977; 57: 889-905.

Distribution of water in Arenicola marina (L.) equilibrated to diluted sea water.

Freeman, R.F.H.; Shuttleworth, T.J.

J. Mar. Biol. Ass. U.K. 1977; 57: 501-519.

Distribution of dry matter between the tissues and coelom in Arenicola marina (L.) equilibrated to dilute sea water.

Freeman, R.F.H.; Shuttleworth, T.J.

J. Mar. Biol. Ass. U.K. 1977; 57: 97-107.

Shuttleworth TJ, Freeman RF

The Journal of experimental biology.. 1974 June 60 (3):769-81. Epub 1900 01 01.

Bioelectric potentials in the gills of the flounder Platichthys flesus.

Shuttleworth, T.J., W.T.W. Potts and J.N. Harris.

J. Comp. Physiol. 1974; 94: 321-329.

Factors affecting the net fluxes of ions in the isolated perfused gills of freshwater Anguilla dieffenbachii.

Shuttleworth, T.J.; Freeman, R.F.H.

J. Comp. Physiol. 1974; 94: 297-307.

The role of the gills in seawater adaptation in Anguilla dieffenbachii. I. Osmotic and ionic composition of the blood and gill tissue.

Shuttleworth, T.J.; Freeman, R.F.H.

J. Comp. Physiol. 1973; 86: 239-313.

The role of the gills in seawater adaptation in Anguilla dieffenbachii. II. Net ion fluxes in isolated perfused gills.

Shuttleworth, T.J.; Freeman, R.F.H.

J. Comp. Physiol. 1973; 86: 315-321.

The role of the gills in seawater adaptation in Anguilla dieffenbachii. III. The relative significance of the gills.

Shuttleworth, T.J.; Freeman, R.F.H.

J. Comp. Physiol. 1973; 86: 323-330.

Shuttleworth TJ

Comparative biochemistry and physiology. A, Comparative

Anchoring protein AKAP79-mediated PKA-phosphorylation of STIM1 determines selective activation of ARC channels, a store-independent Orai channel.

Thompson J.L.; Shuttleworth T.J.

The Journal of Physiology. .

Books

Ion Channels and Transporters in of Epithelia in Health and Disease (2016)

Chapter: Orai Channels

Authors: Shuttleworth, TJ

Publisher: Springer 2016

Current Topics in Membranes (2013)

Chapter: ARC channels – an endogenous store-independent Orai channel

Authors: Thompson, JL; Mignen, O; Shuttleworth, TJ

Publisher: Elsevier Press 2013

Handbook of Cell Signaling (2009)

Chapter: Arachidonic acid-regulated Ca2+ channel

Authors: Shuttleworth, TJ

Publisher: Academic Press 2009

Handbook of Cell Signaling, vol 2 (2003)

Chapter: Arachidonic acid-regulated Ca2+ channel.

Authors: Shuttleworth, T.J.

Publisher: Academic Press 2003

Ionic regulation in animals, (1997)

Chapter: Intracellular signalling in salt-secreting cells - recent advances in the avian nasal gland model

Authors: Shuttleworth, T.J., J.L. Thompson and S.C. Martin

Publisher: Springer Verlag, Berlin 1997

Cellular and Molecular Approaches to Fish Ionic Regulation (1995)

Authors: Wood, C.M., and T.J. Shuttleworth

Publisher: Academic Press, San Diego 1995

Mechanisms of Systemic Regulation: Vol II (1995)

Chapter: Intracellular signals controlling ionic and acid-base regulation in avian nasal gland cells

Authors: Shuttleworth, T.J.

Publisher: Springer Verlag 1995

Handbook of Membrane Channels: Molecular and Cellular Physiology (1994)

Chapter: InsP3 receptor and intracellular Ca2+ release

Authors: Shuttleworth, T.J.

Publisher: Academic Press 1994

Physiology of Elasmobranch Fishes (1988)

Authors: Shuttleworth, T.J

Publisher: Springer Verlag, Berlin. 1988

Physiology of Elasmobranch Fishes (1988)

Chapter: Salt and water balance - Extrarenal mechanisms.

Authors: Shuttleworth, T.J.

Publisher: Springer Verlag, Berlin 1988

Comparative Physiology: Life in Water and on Land (1987)

Chapter: Salt gland function in osmoregulation in terrestrial and aquatic environments.

Authors: Shuttleworth, T.J.

Publisher: Springer Verlag, New York 1987

Transport Processes, Iono- and Osmoregulation (1985)

Chapter: Peptidergic control of transport in the teleost gill

Authors: Shuttleworth, T.J.

Publisher: Springer Verlag, Berlin 1985

Biology in the 80's - Animal Physiology and Biochemistry (1984)

Chapter: Salt secretion and its regulation in vertebrates

Authors: Shuttleworth, T.J.

Publisher: University of Lancaster Press, Lancaster, UK 1984

Gills (1982)

Authors: Houlihan, D.F., J.C. Rankin and T.J. Shuttleworth

Publisher: Cambridge University Press, Cambridge, England. 1982