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Donald L. Gill, PhD

Chairperson, Department of Biochemistry

Professor, Biochemistry

Telephone:  215-707- 3979

Fax:  215-707-2805

Email: dgill@temple.edu

Department of Biochemistry

BSc, Biochemistry, University of Sussex, England, 1972-1975

 

PhD, Biochemistry (Mentor:  Roger P. Ekins, PhD), University of London, England, 1975-1979

 

Postdoctoral Fellowship, National Institutes of Health, Bethesda, MD, Fogarty International Visiting Fellow (Mentor:  Martin Rodbell, PhD, Nobel Laureate), Signal Transduction Mechanisms, 1979-1982

 

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Calcium is one of the most fundamental signaling agents in all animal cells. Cells have evolved to precisely control Ca2+ in the cytoplasm at levels that are 10,000-fold lower than outside cells.  This is accomplished by Ca2+ pumps in the plasma membrane (PM) and endoplasmic reticulum (ER). We study the signals of Ca2+ which occur as a result of control of specific channels in the PM and ER membrane which allow Ca2+ to flow into the cytosol. A slight elevation in the resting cytosolic Ca2+ level is enough to trigger rapid cellular responses such contraction, secretion or changes in the function of key metabolic enzymes. More sustained Ca2+ signals mediate crucial longer term responses including cell growth, cell division, and cell death (apoptosis). My laboratory studies signal transduction, meaning that we study how cells transduce external signals into Ca2+ signals. Cells sense many different external signals through specific receptors for chemical agents such as growth factors, neurotransmitters, and hormones, as well as receptors for temperature, pressure, stretch, sound, and light. The cell converts the message received by receptors into Ca2+ signals by precisely controlling the opening of Ca2+ channels.  My lab uses a combination of molecular biology, biochemistry, cell biology, and single cell physiological approaches to understand how the Ca2+ channels are controlled. We use molecular biology to mutate the channel proteins, create expression vectors, and to modify channel expression using gene silencing approaches. We follow real-time Ca2+ signals in cells by sophisticated single cell ratiometric fluorescence imaging technology.  And we measure the precise biophysical properties of channels using state-of the-art electrophysiological methods. The work centers on the analysis of several distinct types of membrane channels including members of the now widely recognized TRP family of channel proteins involved in transducing a remarkable array of external signals. Our work draws together molecular and cellular approaches to understand the basic function and physiological role of these channels which are critical to mediating essential cellular responses.

How Calcium Signaling Works

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Molecular Biology:

• Plasmid construction
• Mutational analysis
• Real-time PCR
• Yeast 2-hybrid approaches
• Gene silencing techniques

Biochemistry:

• Gel electrophoresis
• Western analysis
• Enzyme analysis
• Surface biotinylation

Cell Biology:

• Single cell imaging
• Immunocytochemistry
• Ratiometric fluorescence imaging
• Confocal microscopy

Biophysics:

• Electrophysiological recording of ion channels
• Single cell patch clamp recording
• Isolated patch analysis
• Single channel analysis

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19889372. Mancarella S, Wang Y, Gill DL, Calcium signals: STIM dynamics mediate spatially unique oscillations. Curr Biol 19:20(R950-2)2009 Nov 3

19487696. Zhou Y, Mancarella S, Wang Y, Yue C, Ritchie M, Gill DL, Soboloff J, The short N-terminal domains of STIM1 and STIM2 control the activation kinetics of Orai1 channels. J Biol Chem 284:29(19164-8)2009 Jul 17

19473984. Deng X, Wang Y, Zhou Y, Soboloff J, Gill DL, STIM and Orai: dynamic intermembrane coupling to control cellular calcium signals. J Biol Chem 284:34(22501-5)2009 Aug 21

19376967. Wang Y, Deng X, Zhou Y, Hendron E, Mancarella S, Ritchie MF, Tang XD, Baba Y, Kurosaki T, Mori Y, Soboloff J, Gill DL, STIM protein coupling in the activation of Orai channels. Proc Natl Acad Sci U S A 106:18(7391-6)2009 May 5

19272522. Graham SJ, Black MJ, Soboloff J, Gill DL, Dziadek MA, Johnstone LS, Stim1, an endoplasmic reticulum Ca2+ sensor, negatively regulates 3T3-L1 pre-adipocyte differentiation. Differentiation 77:3(239-47)2009 Mar

18782202. Wang Y, Deng X, Hewavitharana T, Soboloff J, Gill DL, Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle. Clin Exp Pharmacol Physiol 35:9(1127-33)2008 Sep

18635545. Hewavitharana T, Deng X, Wang Y, Ritchie MF, Girish GV, Soboloff J, Gill DL, Location and function of STIM1 in the activation of Ca2+ entry signals. J Biol Chem 283:38(26252-62)2008 Sep 19

18096706. Spassova MA, Hewavitharana T, Fandino RA, Kaya A, Tanaka J, Gill DL, Voltage gating at the selectivity filter of the Ca2+ release-activated Ca2+ channel induced by mutation of the Orai1 protein. J Biol Chem 283:22(14938-45)2008 May 30

17905723. Parvez S, Beck A, Peinelt C, Soboloff J, Lis A, Monteilh-Zoller M, Gill DL, Fleig A, Penner R, STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. FASEB J 22:3(752-61)2008 Mar

17602740. Hewavitharana T, Deng X, Soboloff J, Gill DL, Role of STIM and Orai proteins in the store-operated calcium signaling pathway. Cell Calcium 42:2(173-82)2007 Aug

17217080. Soboloff J, Spassova M, Hewavitharana T, He LP, Luncsford P, Xu W, Venkatachalam K, van Rossum D, Patterson RL, Gill DL, TRPC channels: integrators of multiple cellular signals. Handb Exp Pharmacol :179(575-91)2007

17084918. Soboloff J, Spassova MA, Dziadek MA, Gill DL, Calcium signals mediated by STIM and Orai proteins--a new paradigm in inter-organelle communication. Biochim Biophys Acta 1763:11(1161-8)2006 Nov

17056714. Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL, A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci U S A 103:44(16586-91)2006 Oct 31

16860747. Soboloff J, Spassova MA, Hewavitharana T, He LP, Xu W, Johnstone LS, Dziadek MA, Gill DL, STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Curr Biol 16:14(1465-70)2006 Jul 25

16840689. Gill DL, Spassova MA, Soboloff J, Signal transduction. Calcium entry signals--trickles and torrents. Science 313:5784(183-4)2006 Jul 14

16766533. Soboloff J, Spassova MA, Tang XD, Hewavitharana T, Xu W, Gill DL, Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem 281:30(20661-5)2006 Jul 28

16537481. Spassova MA, Soboloff J, He LP, Xu W, Dziadek MA, Gill DL, STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels. Proc Natl Acad Sci U S A 103:11(4040-5)2006 Mar 14

16204251. Soboloff J, Spassova M, Xu W, He LP, Cuesta N, Gill DL, Role of endogenous TRPC6 channels in Ca2+ signal generation in A7r5 smooth muscle cells. J Biol Chem 280:48(39786-94)2005 Dec 2

16122132. Weiss MR, Gill DL, What goes around comes around: re-emerging themes in sport and exercise psychology. Res Q Exerc Sport 76:2 Suppl(S71-87)2005 Jun

15647288. He LP, Hewavitharana T, Soboloff J, Spassova MA, Gill DL, A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2. J Biol Chem 280:12(10997-1006)2005 Mar 25

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