University of Rochester Medical School Date 07/13/2010 CURRICULUM VITAE Name Address: David Ian Yule Home Office E-Mail 33 Corral Drive, Penfield, NY. Department of Pharmacology and Physiology, University of Rochester, Medical School, 601 Elmwood Ave, Rochester, NY. Zip 14526 Phone 585-670-0394 Zip 14642 Phone 585-273-2154 FAX 585-273-2652 [email protected] Date of Birth 11-16-1964 Place of Birth Edinburgh, Scotland Citizenship British Social Security No. 372111766 Resident Alien No A070548059 EDUCATION School or College Field of Study Degree Earned Year Portsmouth Polytechnic, U.K. Pharmacology BSc (hons) 1986 University of Liverpool, U.K. Physiology PhD. Mentor D.V Gallacher 1990 POSTDOCTORAL TRAINING M.R.C. Secretory Control Group, Physiology Department, University of Liverpool. Supervisor Prof. O.H Petersen, (1990) Department of Physiology, University of Michigan. Supervisor Prof. J.A.Williams. (1990-1992). 1 FACULTY APPOINTMENTS Institution Rank Year(s) University of Rochester Professor 2009- Secondary Appointments; Department of Internal Medicine (Digestive Diseases and Liver Unit) and the Center for Oral Biology Associate Professor 2003-2009 Unlimited Tenure Oct 2005 Assistant Professor 1998-2003 University of Michigan Assistant Professor 1996-1998 University of Michigan Assistant Research Scientist 1994-1998 University of Michigan Research Investigator 1992-1994 University of Rochester MEMBERSHIP IN NATIONAL AND INTERNATIONAL ACADEMIC PROFESSIONAL ORGANIZATIONS Organization Year(s) American Physiological Society. 1996-present American Gastroenterological Association 1999-present American Society for Biochemistry and Molecular Biology 2003-present Biochemical Society (U.K.) 2003-present Biophysical Society 2006-present EDUCATIONAL CONTRIBUTIONS Medical student teaching 1999: Human Structure and Function, Block 4-Gastrointestinal Physiology. 2 Lectures “Digestion and Absorption I and II.” (2 hours). Human Structure and Function, PBL Tutor. Gastrointestinal case. (6 hours). 2000. Human Structure and Function, Block 4-Gastrointestinal Physiology. 2 Lectures “Digestion and Absorption I and II.” (2 hours). Human Structure and Function, PBL Tutor. Gastrointestinal block case (6 hours.) Renal block case. (6 Hours). 2 Endocrinology block case. (6 hours). 2001. PBL Tutor 2nd year pharmacology case. (6 hours). Human Structure and Function, Block 4-Gastrointestinal Physiology. 2 Lectures “Digestion and Absorption I and II.” (2 hours). Human Structure and Function, PBL Tutor. Gastrointestinal block case (6 hours.) Renal block case. (6 Hours). Endocrinology block case. (6 hours). 2002. PBL Tutor, Year 2 case seminars pharmacology case (6 hours). PBL Tutor, Year 2 Case seminars physiology case (6 hours). Human Structure and Function, Block 4-Gastrointestinal Physiology. 2 Lectures “Digestion and Absorption I and II.” (2 hours). Human Structure and Function, PBL Tutor. Gastrointestinal block case. (6 hours). Renal block case. (6 Hours). 2003. PBL Tutor, Year 2 Case seminars physiology case. (6 hours). Human Structure and Function, Block 4-Gastrointestinal Physiology. 2 Lectures “Digestion and Absorption I and II.” (2 hours). Human Structure and Function, PBL Tutor. Gastrointestinal block case (6 hours.) Renal block case. (6 Hours). 2004. PBL Tutor, Year 2 Case seminars physiology case. (6 hours). Human Structure and Function, Block 4-Gastrointestinal Physiology. 3 Lectures; Pancreatic and Billary Secretion” and “Digestion and Absorption I and II.” (3 hours). Human Structure and Function, PBL Tutor. Gastrointestinal block case. (4 hours.). Renal block case. (6 Hours). 2005. PBL Tutor, Year 2 Case seminars physiology case. (6 hours). Human Structure and Function, Block 4-Gastrointestinal Physiology. 3 Lectures; Pancreatic and Billary Secretion” and “Digestion and Absorption I and II.” (3 hours). Human Structure and Function, PBL Tutor. 4 PBLs (total 22 hrs) 2006. Human Structure and Function, Block 4-Gastrointestinal Physiology. 4 Lectures;,“G.I Motility”, Pancreatic and Billary Secretion” and “Digestion and Absorption I and II.” (4 hours). Human Structure and Function, PBL Tutor. 4 PBLs (total 22 hrs) 2007 Human Structure and Function, Block 4-Gastrointestinal Physiology. 5 Lectures; “Introduction to GI Physiology”, “G.I Motility”, Pancreatic and Billary Secretion” and “Digestion and Absorption I and II.” (5 hours). Human Structure and Function, PBL Tutor. 2 PBLs (total 10 hrs) 3 Medical Pharmacology PBL Tutor (6 hrs) 2009 Human Structure and Function, Block 4-Gastrointestinal Physiology. 5 Lectures; “Introduction to GI Physiology”, “G.I Motility”, Pancreatic and Billary Secretion” and “Digestion and Absorption I and II.” (5 hours). Human Structure and Function, PBL Tutor. 2 PBL (total 10 hrs) Graduate student teaching 1998. IND 409. Cell Biology. Small group leader. (2 hours). Course Director Pharmacology and Physiology Colloquium. 1999. IND 409. Cell Biology. Small group leader. (2 hours). IND 447. Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). IND 447. Recitation “The role of targeting in signal transduction”. (1.5 hour). 2000. IND 447. Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). IND 447. Recitation “The role of targeting in signal transduction”. (1.5 hour). 2001. IND 447. Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). IND 447. Recitation “The role of targeting in signal transduction”. (1 hour). PHP 407. “Digestion and absorption” lecture. (1 hour). PHP550. Ion Channels and Disease. (1.5 hours) 2002. IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). IND 447 Recitation “The role of targeting in signal transduction”. (1.5 hour). 2003. IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). IND 447 Recitation “The role of targeting in signal transduction”. (1.5 hour). PHP 550. Ion Channels and disease. (3 hours). 2004. MBI 579 Salivary Glands and Saliva. “Calcium signaling in salivary acinar cells”. (1.5 hours) IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). PHP 530 Advanced Topics in Pharmacology. “The gastric system-gastric ulcers and GERD”. Facilitator (4 hours). IND 501 Ethics and Professional Integrity in Research. (Facilitator, 2 hours). 2005. IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) 4 IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). PHP 550. Ion Channels and disease. (3 hours). 2006 IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). PHP 403 Protein secretion 2 lectures (3 Hours) 2007 IND447 Signal Transduction. Course Director IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). PHP 403 Cell and Molecular Physiology. Protein secretion 2 lectures (3 Hours) 2008 IND447 Signal Transduction. Course Director IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) IND 447 Signal Transduction. “Spatial organization of signaling” 1 lecture. (1.5 hours). 2009 IND 447 Signal Transduction. “Structure, Expression and Regulation of InsP3R”. (1.5 hours) IND 447 Signal Transduction. “Spatial organization of signaling” 2 lectures. (3 hours). PHP 403 Cell and Molecular Physiology. Protein secretion 2 lectures (3 Hours) Graduate and postdoctoral training 1999 Rotation students-Hoffman Lantum, Steven Straub. Thesis Advisor-Stephen Straub. Postdoctoral-Dr. David Giovannucci. 2000 Thesis Advisor-Stephen Straub (Cell and Molecular Biology Training Grant). Postdoctoral-Dr. David Giovannucci, Dr Jason Bruce. 2001 Rotation Students-Ondina Lungu, Joey Chen. Thesis Advisor –Stephen Straub (Cell and Molecular Biology Training Grant). Postdoctoral-Dr. David Giovannucci, Dr Jason Bruce. 2002 Rotation Students-Denia Ramirez, David Brown. Thesis Advisor-Stephen Straub (Cell and Molecular Biology Training Grant). Thesis Advisor-David Brown (Cell and Molecular Biology Training Grant). Postdoctoral-Dr Jason Bruce. 2003. Rotation students-Jenifer Butler. Thesis Advisor-Steve Straub (Cell and Molecular Biology Training Grant). Thesis Advisor-David Brown (Cell and Molecular Biology Training Grant). Postdoctoral-Dr Jason Bruce. 5 2004. Rotation Students-Matt Betzenhauser, Julien Sebag, Keigan Park. Thesis Advisor-David Brown (Cell and Molecular Biology Training Grant). Thesis Advisor-Matt Betzenhauser (Cell and molecular biology Training Grant). Postdoctoral-Dr Stephen Straub (Cell and Molecular Biology Training Grant). Postdoctoral-Dr Jason Bruce. Postdoctoral Dr Vitaliy Resnikov. Postdoctoral Jong-Won Hak. 2005. Rotation Students-Ryan Loy Thesis Advisor-David Brown Thesis Advisor-Matt Betzenhauser Thesis CoAdvisor-Keigan Park Postdoctoral Advisor Jong-Won Hak. 2006 . Thesis Advisor-David Brown Thesis Advisor-Matt Betzenhauser Thesis CoAdvisor-Keigan Park Postdoctoral Advisor Jong-Won Hak. 2007. Rotation students-Meital Gabal Thesis Advisor-Matt Betzenhauser Thesis CoAdvisor-Keigan Park Postdoctoral Advisor -Jong-Won Hak. 2008 Rotation student Elaina Rotation student Wayne Thesis Advisor-Matt Betzenhauser Thesis Co-Advisor-Keigan Park Postdoctoral Advisor Jong-Hak Won Postdoctoral Advisor-Watura Masuda SERVICE ASSIGNMENTS AND RESPONSIBILITIES OF LAST FIVE YEARS Editorial Board Journal of Biological Chemistry. 2003-2008. World Journal of Gastroenterology 2004Cell Calcium 2008Editorial Advisory Board Biochemical Journal. 2003Ad Hoc Reviewer for: Nature 6 Science EMBOJ Journal of Cell Biology Gastroenterology. Journal of Pharmacology and Experimental Therapeutics. Journal of General Physiology. Journal of Clinical Investigation. Journal of Neurochemistry. Journal of Cellular Physiology. Journal of Molecular Endocrinology. Biochemica Biophysica Acta. Proceeding of the National Academy (USA). Cell Calcium. Peptides. PROFESSIONAL ADMINISTRATIVE ASSIGNMENTS AND RESPONSIBILITIES 1998. Department of Pharmacology and Physiology Admissions Committee. 1998-present. Real Time Confocal Core committee member. 1999. Cell Regulation Molecular Pharmacology Cluster Admissions committee. 2000. Cell Regulation Molecular Pharmacology Web-Page committee. 2000. Admissions Director Cell Regulation Molecular Pharmacology. 2000-present. Department of Pharmacology and Physiology Graduate Studies committee member. 2001-2006 Cellular and Molecular basis of Medicine Cluster Director. 2003- present Department of Pharmacology and Physiology faculty search committee. 2007-2009 Course Director IND 447 Signal Transduction 2007-present. Oversight Committee Confocal Microscope Core 2007-2009 Gastroenterology Division Chief Search Committee 2008-present Co-Scientific Director Confocal Microscope Core 2009-Present. Director, Cellular and Molecular Pharmacology and Physiology Program RESEARCH ACTIVITIES OF LAST FIVE YEARS 2 R01 DK054568-10 (Yule, PI) 09/01/2008 – 04/30/2013 NIH/NIDDK Pancreatic Function: G Protein-Mediated Ca2+ Signaling This project involves determining if Inositol 1,4,5-trisphosphate receptor phosphorylation play an important role in defining the differing [Ca2+]i signals stimulated by peptides and neurotransmitters in pancreatic acinar cells. 06/01/2008 – 06/30/2012 1 RO1 DE14756 (Yule, PI) NIH/NIDCR [Ca2+]i and Secretory Dynamics in Parotid Acinar Cells The long term goal of this grant is to elucidate the role of cytosolic calcium dynamics in the control of both fluid and exocytotic secretion. The processes which underlie initiation, propagation and termination of calcium 7 signals in parotid will be determined and the role these signaling characteristics play in mediating fluid and protein secretion will be determined. No overlap. R01 DE16999 (Shuttleworth, PI; Yule, Co-investigator) NIH/NIDCR Signaling pathways in salivary gland fluid secretion 01/07/2005 – 06/30/2010 The major goals of this project are to characterize and define the molecular mechanisms underlying regulation of intracellular Ca2+ signals in the parotid acinar cells and the consequences of these events for salivary fluid secretory mechanisms. No overlap 1 RO1 DE016960 (Begenisich, PI; Yule, Co-investigator) NIH/NIDCR The Physiological Roles of K Channels in Fluid Secretion 01/03/2006 – 02/28/2011 The goal of the studies is to understand the physiological roles of the Ca2+-activated K channels that are expressed in salivary glands. This Ca2+willbe accomplished with molecular, genetic, biochemical, optical, and electrophysiological approaches to test for their co-localization and to understand their Ca2+ sensitivities and the mechanism of their interaction. The studies also include examining physiological fluid secretion in K channel deficient mice and testing the applicability of the results with the mouse system to human parotid function. No overlap. R01 DE019245 Bengenisich/Sneyd, PI; Yule Co-Investigator NIH/NIDCR An Experimental/Computational Approach for Understanding salivary Fluid Secretion 08/15/08-06/30/13 This project involves the developments of a multi-scale and computational model describing the molecular basis of fluid secretion by the salivary glands incorporating the synergies between different signaling pathways and effector molecules, and at different levels of cellular organization – from individual acinar and duct cells, to the prototypical secretory unit of the acinus and its associated duct. Throughout, the model predictions will be evaluated against relevant experimental data, and will be used to develop further experiments and hypothesis of salivary gland function. COMPLETED. 1 PO1 DE13539 (Melvin, PI; Yule, Co-PI on Subproject 1) 04/01/2000 – 03/31/2005 NIH/NIDCR Molecular Basis of Idiopathic Dry Mouth Subproject 1: Salivary Gland Hypofunction: Genetic defects in Signaling Crosstalk This project examined the hypothesis that disruptions in the cellular mechanisms responsible for the cAMP-mediated potentiation of [Ca2+]i-dependent fluid secretion in the salivary glands underlies many cases of idiopathic dry-mouth. To this end we are studying the biochemical, ultrastructural, and molecular basis for the cAMP-dependent potentiation of intracellular Ca2+ signals in parotid salivary gland cells and the interactions between these two signals on various effector proteins involved in the fluid secretory process. R56DK054568-10 (Yule, PI) 09/01/2007-08/31/2008 8 Pancreatic Function: G Protein-Mediated Ca2+ Signaling This award represents NIH Director’s Bridging funds to support DK054568-10. 2R56DE014756-06 (Yule, PI) 07/01/2007-06/30/2008 NIH/NIDCR [Ca2+]i and Secretory Dynamics in Parotid Acinar Cells This award represents NIH Director’s Bridging funds to support DE14756. INVITED LECTURES DURING LAST FIVE YEARS Salivary Glands and Exocrine secretion Gordon Conference. Session Co-chair and Invited speaker. Ventura CA. Feb 2005. “Regulation of InsP3R by phosphorylation and ATP. Invited speaker. School of Biological Sciences. University of Manchester. March 2006. “cAMP and Calcium Signaling in Exocrine Cells” Digestive Disease Center, Yale University. March 2005. “Calcium signaling in parotid acinar cells”- Invited speaker Stensen III symposium Ozazaki, Japan, October 2006. Salivary Glands and Exocrine Secretion Gordon Conference. Feb 2007 Invited Speaker and Meeting Co-Chair 2007; Chair 2009. Regulation of InsP3R by Phosphorylation and ATP. Department of Physiology, University of Oxford, UK. March 2007. “Regulation of InsP3R by Phosphorylation” Invited Speaker. Calcium Signaling Gordon Research Conference. Tilton, New Hampshire. July 2007. Ca2+ signaling dynamics in exocrine acinar cells. Invited Speaker. Microscopy and Microanalysis 2007. Ft Lauderdale Florida. August 2007. Regulation of InsP3R by ATP and phosphorylation. Department of Physiology. Baylor School of Medicine. Oct 2007. Single Channel Recordings of InsP3R. Invited Speaker. Calcium and Calcium Binding Protein Meeting. La Palma, Canary Islands, Spain. Oct 2007. Regulation of InsP3R in Salivary Acinar Cells. NIDCR Intramural program. NIH, Bethesda MD. Feb 2008 Generating Specificity in Intracellular Ca2+ Signals. Department of Physiology, Emory University. May 2008 Regulation of Ca2+ Release in Salivary Glands. Rochester Oral Biology Conference: Salivary Glands and Saliva. June 2008. 9 Regulation of Calcium Release by ATP in pancreatic acinar cells: American Pancreatic Association. Chicago. Nov 2008. Cross Talk between the cAMP and Calcium Signaling Systems. Berlin Universities Insect Physiology Graduate Program. Berlin, Germany, Nov 2008. Chair, Gordon Research Conference; Salivary Glands and Exocrine Secretion. Galveston TX Feb 2009 Regulation of Ca2+ Release by PKA mediated Phosphorylation. Pharmacology Dept. University of North Dakota, Grand Forks ND. March 2009. Regulation of Ca2+ release by ATP. Current Topics in Calcium Signaling. Ouro Preto, Brazil. April 2009. Defining Signaling Specificity by Regulation of Ca2+ Release. Calcium Signaling Gordon Conference. Barga Italy, June 2009. Regulation of Ca2+ Release by Cyclic Nucleotide Dependent Kinases. Calcium and Calcium Binding Protein Meeting. Pucon, Chile, Nov 2009. Rules for the regulation of Ca2+ release by PKG and PKA. Department of Pharmacology, University of Cambridge, UK. April 2010. Ca2+ Signaling Dynamics in Pancreatic Stellate Cells. FASEB Summer Conference on Calcium and Cell Function. Steamboat Springs, CO, June 2010. Fine Tuning Ca2+ Signaling by Regulation of Ca2+ Release. International Congress on Cell Membranes and Oxidative Stress. Isparta, Turkey. June 2010. MEMBERSHIP AND PARTICIPATION IN NATIONAL ADVISORY AND HEALTH COUNCILS AND RESEARCH REVIEW COMMITTEES Dec 1999 and Jan 2001 (resubmission). Special emphasis panel for NIH (NIDDK). (review of program project grant entitled “Nuclear calcium signaling in Liver”). 2000-2002- Ad Hoc reviewer for the Veterans Administration. Aug 2002-Reviewer for NIH (NIDDK) RFA “Comprehensive Programs in Beta Cell Biology”. Aug 2002-Present Program Grant reviewer for Medical Research Council (United Kingdom). Feb 2004-Temporary member CDF-3 NIH study section. June 2004-Temporary member ODCS NIH study section. Aug 2004-Member of NIH (NIDCR) spatial emphasis panel. OCT 2004 -Member of NIH (NIDCR) spatial emphasis panel. Nov 2004-Member of NIH (NIGMS) special emphasis panel. 10 Sep 2005- Member of NIH (NIGMS) special emphasis panel (microscopy shared equipment) Dec 2005- Member of NIH (DIDDK) special emphasis panel (PO1 submissions) Feb 2006- Member of NIH (NIDCR) Sjogren Syndrome RFA review committee Aug 2007- Chair of NIH (NIDCR) Special Emphasis panel on ALSG syndrome Sep 2007-Temporary Member ODCS NIH study section. Feb 2008-Temporary Member NIRC NIH study section. May 2008. Member Bion-1 review group NASA study section June 2008 Temporary Member OCDS NIH study section June 2009-Chartered Member ODCS NIH study section. PATENTS "Inositol 1,4,5-Trisphosphate Receptor Mutants and Uses Thereof" Tech ID 1282 filed Jan 26th 2004. PUBLICATIONS Original articles 1. Yule D.I., Gallacher D.V. Oscillations of cytosolic Ca2+ in single pancreatic acinar cells stimulated by acetylcholine. FEBS Lett. 239:358-263, 1988. 2. Martin, S.C., Yule D.I., Dunne M.J., Gallacher D.V., Petersen O.H. Vasopressin directly closes ATP sensitive K+ channels evoking membrane depolarisation and an increase in [Ca2+]i in insulin secreting cells. EMBO J. 8:3595-3599, 1989. (Equal primary authors). 3. Gallacher D.V., Hanley M.R., Petersen O.H., Roberts M.L., Squire-Pollard L., Yule D.I. Substance P and bombesin elevate [Ca2+]i by different molecular mechanisms in the AR42J pancreatic acinar cell line. J. Physiol. 426:193-207, 1990. 4. Dunne M.J., Yule D.I., Gallacher D.V., Petersen O.H. Stimulus-evoked depolarization and increase in [Ca2+]i in insulin-secreting cells is dependent on extracellular Na+. J.Memb. Biol. 113:131-138, 1990. 5. Dunne M.J., Yule D.I. Gallacher D.V., Petersen O.H. Comparative study in the effects of chromakalim (BRL 34915) and diazoxide on membrane potential, [Ca2+]i and ATP-dependent potassium currents in insulin secreting cells. J. Memb. Biol. 114:53-60, 1990. 6. Osipchuk U.V., Wakui M., Yule D.I., Gallacher D.V., Petersen O.H. Cytoplasmic Ca2+ oscillations evoked by receptor stimulation, G-protein activation, internal application of inositol trisphosphate or Ca2+: Simultaneous microfluorimetry and Ca2+ dependent Cl-current measurement in single pancratic acinar cells. EMBO J. 9:697-704, 1990. 7. Petersen, O.H., Wakui, M., Osipchuk, Y., Yule, D.I. and Gallacher, D.V. Electrophysiology of pancreatic acinar cells. Methods in Enzymology. 192 300-308. 1990. 11 8. Yule D.I. and Williams J.A. Mastoparan induces oscillations of cytosolic Ca2+ in rat pancreatic acinar cells. Biochem Biophys. Res. Commun. 31:159-165, 1991. 9. Dunne M.J., Yule D.I., Gallacher D.V., Petersen O.H. Effects of alanine on insulin-secreting cells: Patchclamp and single cell intracellular Ca2+ measurements. Biochim. Biophys. Acta 1055:157164, 1991. 10. Yule D.I., Lawrie A.M., Gallacher D.V. Acetylcholine and cholecystokinin induce different patterns of oscillating calcium signals in pancreatic acinar cells. Cell Calcium 12:45-51, 1991. 11. Petersen O.H., Gallacher D.V., Wakui M, Yule D.I., Petersen C.C., Toescu E.C. Receptor-activated cytoplasmic Ca2+ oscillations in pancreatic acinar cells: Generation and spreading of Ca2+ signals. Cell Calcium 12:135-144, 1991. 12. Yule D.I., Blevins G.T., Wagner A.G., Willliams J.A. Endothelin increases Ca2+ in rat pancreatic acinar cells by intracellular release but fails to induce amylase secretion. Biocim.Biophys.Acta.1136. 175-180. 1992. 13. Wagner, A.C.C. Wishart, M., Yule, D.I. and Williams, J.A. Effects of okadaic acid on protein phosphorylation and amylase release indicate a role for dephosphorylation in pancreatic stimulus secretion coupling. Am.J.Physiol. 263. C1172-1180. 1992. 14. Yule, D.I. and Williams, J.A. U73122 inhibits Ca2+-oscillations in response to CCK and Carbachol but not to JMV-180 in rat pancreatic acinar cells. J.Biol.Chem. 267.(20). 13830-13835. 1992. 15. Yule, D.I., Essington, T.E. and Williams J.A. Pilocarpine and carbachol exhibit markedly different patterns of Ca2+ signaling in rat pancreatic acinar cells. Am.J.Physiol. (G.I.) 264. G786-G791. 1993 16. Yule, D.I., Wu, D., Essington, T.E., Shayman, J.A. and Williams, J.A. Sphingosine metabolism induces Ca2+ oscillations in rat pancreatic acinar cells. J.Biol. Chem. 268.(17) 12353-12358. 1993. 17. R-D. Duan, Wagner, A.C.C., Yule, D.I. and Williams, J.A. Multiple inhibitory effects of genestein on stimulus secretion coupling in rat pancreatic acini. Am.J.Physiol. 266 G303-G310. 1994. . 18. Yule, D.I., Tseng, M-J., Williams, J.A. and Logsdon. C.D. A cloned CCKA receptor transduces multiple signals in response to full and partial agonists. Am.J.Physiol. 265. G999-G1004. 1993. 19. Blevins, G.T., Van de Westerlo, E.M.A., Yule, D.I. and Williams, J.A. Characterization of CCKA receptor activity by a family of CCKB receptor antagonists. J. Pharmacol. Exp. Ther. 269. 3. 911-916. 1994. 20. Yule, D.I and Williams J.A. CCKA antagonists reveal that JMV-180 and CCK bind to different sites on the CCKA receptor. Peptides. 15. 1045-1051. 1994. 21. Yule, D.I., Kim, E. and Williams, J.A. Tyrosine kinase inhibitors attenuate capacitative Ca2+ influx in rat pancreatic acinar cells. Biochem.Biophys.Res.Comm. 1994. 202 .1697-1704. 1994. 22. Palmer, R.K., Yule, D.I. Williams, J.A. and Fisher, S.K. Agonist -specific calcium signalling and phosphoinositide hydrolysis in human Sk-N-MCIXC neuroepithelioma cells. J. Neurochemistry. 63. 2099-2107. 1994. 23. Simeone, D.M., Yule, D.I., Logsdon C.D. and Williams, J. A. Ca2+ signalling through secretagogue and growth factor receptors on pancreatic AR4-2J cells. Regulatory Peptides. 55. 197-206. 1995. 24. Yang, J., Williams, J.A., Yule, D.I. and Logsdon, C.D. Mutation of carboxy terminal threonine residues in human m3 muscarinic acetylcholine receptor modulates the extent of sequestration and desensitization. Molecular Pharmacology. 48. 477-485. 1995. 12 25. Massa, E., Kelley, K., Yule, D.I., Macdonald, R. and Uhler. M. Comparison of fura-2 imaging and electrophysiological analysis of murine 1 subunits coexpressed with novel 2 calcium channel isoform subunits. Molecular Pharmacology. 47:707-717. 1995. 26. Deutsch, D., Williams, J.A. and Yule, D.I. Halothane and Octanol block Ca2+ oscillations in pancreatic acini by multiple mechanisms. Am. J. Physiol. 269 G779-G788. 1995.. 27. Kimbell, E., Yule, D.I. and Mulholland, M. Extracellular ATP mediates Ca2+ signaling in cultured myenteric neurons via a phospholipase C dependent mechanism. Am. J. Physiol. G587-G593. 270.33.1996. 28. Kimbell, E., Yule, D. I. and Mulholland, M. Caffeine and Ryanodine sensitive calcium stores in cultured myenteric neurons. Am. J. Physiol. G594-G603. 270. 33. 1996. 29. Palmer, R.K., Yule, D.I., Williams, J.A. and Fisher, S.K. Paracrine mediation of calcium signaling in SKN-MCIXC neuroepitheliioma cells. Am.J. Physiol. 271 C43-C53. 1996. 30. Yule, D.I. Steunkel, E. and Williams, J.A. Intercellular Ca2+ waves in pancreatic acini: mechanism of transmission. Am. J. Physiol. 271. C1285-1294. 1996. 31. Yule, D.I, Ernst, S.A., Onishi, H., and R. Wojiciewicz. Evidence that zymogen granules are not a physiologically relevant Ca2+ pool: defining the distribution of inositol 1,4,5-trisphosphate receptors in pancreatic acinar cells. J. Biol. Chem. 272. 9093-9098. 1997. 32. Ohnishi, H., Ernst, S.A., Yule, D.I., Baker, C. and Williams J.A. Heterotrimeric G-protein Gq/ll localized on pancreatic zymogen granules is involved in calcium regulated amylase secretion. J. Biol. Chem. 272. 16056-16061. 1997. 33. Zhang, W. Sarosi, G, Barnhart, D. Yule, D.I. and Mulholland M. Endothelin activated calcium signaling in enteric glia derived from neonatal guinea pig. Am. J. Physiol. 272. G1175-G1185. 1997. 34. Detjen, K. Yule, D.I., Tseng, M-J., Williams, J.A., and Logsdon, C. CCK B receptors activate similar second messenger systems but have opposite growth effects in CHO and Swiss 3T3 cells. Am. J. Physiol. 273:C1449-57, 1997. 35. Ohnishi H. Samuelson LC. Yule D.I., Ernst SA. and Williams JA. Overexpression of Rab3D enhances regulated amylase secretion from pancreatic acini of transgenic mice. J. Clin. Invest. 100:3044-52, 1997. 36. Giovannucci, D.R., Yule, D.I. and Stuenkel E.R. Optical measurement of stimulus-evoked membrane dynamics in single pancreatic acinar cells. Am. J. Physiol. 275. C732-C739. 1998. 37. Yule, D.I., Baker, C.W., Park, N. and J.A. Williams. Calcium signaling in rat pancreatic acinar cells: a role for Gq, G11 and G14. Am. J. Physiol. 276.G271-G279. 1999. 38. Wojcikiewicz, R.H., Ernst, S.A. and Yule D.I. Secretagogues cause ubiquitination and down-regulation of inositol 1,4,5 trisphosphate receptors in rat pancreatic acinar cells. Gastroenterology. 116. 11941201.1999. 39. LeBeau*, A., Yule*, D.I. Groblewski*, G.E. and J. Sneyd. Agonist specific calcium oscillations in pancreatic acinar cells: a role for phosphorylation of the inositol 1,4,5-trisphosphate receptor. J. General Physiol. 113. 851-871. 1999. (*equal primary authors). 40. Sneyd, J. LeBeau, A. and Yule D.I. Traveling waves of Calcium in Pancreatic acinar cells: Model construction and bifurcation analysis. Physica D. 145. 158-179. 2000. 13 41. Giovannucci, D.R. Groblewski, G.E. Sneyd, J. and Yule D.I. Targeted phosphorylation of inositol trisphosphate receptors selectively inhibits localized calcium release and shapes oscillatory calcium signals. J. Biol. Chem. 275(43) 33704-33711. 2000. 42. Straub S. Giovannucci, D.R. and Yule D.I. Calcium wave propagation in pancreatic acinar cells: functional interaction of Inositol trisphosphate receptors, ryanodine receptors and mitochondria. J. General Physiol. 116. 547-559. 2000. 43. Beutner G, Sharma VK, Giovannucci DR, Yule D.I, Sheu SS. Identification of a ryanodine receptor in rat heart mitochondria. J Biol Chem 276(24):21482-8. 2001. 45. Bruce, J.I.E. Shuttleworth T.J., Giovannucci DR. and Yule D.I. Phosphorylation of inositol 1,4,5trisphosphate receptors in parotid acinar cells: A mechanism for the synergistic effects of cAMP on Ca2+ signaling. J. Biol. Chem. 277. 1340-1348. 2002. 46. Giovannucci, D.R., Bruce, J.I.E., Straub, S.V., Arreola, J., Sneyd, J., Shuttleworth, T.J. and Yule D.I. Cytosolic Ca2+ and Ca2+-activated Cl- Current Dynamics: Insights from Two Functionally Distinct Mouse Exocrine Cells. J. Physiol. 540. 469-484. 2002. 47. Straub, S.V., D.R. Giovannucci, J.I. Bruce, and Yule, D.I. A role for phosphorylation of inositol 1,4,5trisphosphate receptors in defining calcium signals by peptide agonists in pancreatic acinar cells. J Biol. Chem. 277: 31949-31956. 2002. 48. Bruce, J. I.E, Yule, D.I and Shuttleworth, T.J. Ca2+-dependent, protein kinase-A modulation of the plasma membrane Ca2+-ATPase in parotid acinar cells. J. Biol. Chem. 277. 48172-488181. 2002. 49 Domotor E, Benzakour O, Griffin JH, Yule D, Fukudome K, Zlokovic BV. Activated Protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of Protease Activated Receptor. Blood. 101: 4797-4801. 2003. 50. Sneyd, J., Tsaneva-Atanaova, K., Bruce, J.I.E, Straub, S., Giovannucci, D.R. and Yule, D.I. A model for calcium waves in pancreatic and parotid acinar cells. Biophysical J. 85. 1392-1405. 2003. 51. Brown, D.A. Melvin, J.E. and Yule, D.I. A critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells. Am. J. Physiol. 285. G804-G812. 2003. 52. Wagner L.E. Li, W-H, and Yule D.I. Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases: A mutational analysis of the functionally important sites in the S2+ and S2- splice variants. J. Biol. Chem. 278. 45817-45817. 2003. 53. Bruce, J.I.E, Giovannucci , D.R, Blinder, G., Shuttleworth, T.J and Yule, D.I. Modulation of [Ca2+]i signaling dynamics and metabolism by perinuclear mitochondria in mouse parotid acinar cells. J. Biol. Chem. 279. 12909-12917. 2004. 54. Sneyd J, Tsaneva-Atanasova K, Yule DI, Thompson JL, Shuttleworth TJ. Control of calcium oscillations by membrane fluxes. Proc. Nat. Acad. Sci (USA).101(5):1392-6. 2004. 55. Brown, D.A. Bruce, J.I.E. Straub, S.V. and Yule, D.I. c AMP potentiates ATP-evoked calcium signaling in human parotid acinar cells. J Biol. Chem. 279: 39485 – 39494. 2004. 56. Wagner, L.E. Li, W-H., Joseph, S.K. and Yule, D.I. Functional consequences of phosphomimetic mutations at key phosphorylation sites in the type-1 inositol 1,4,5-trisphosphate receptor. J. Biol. Chem. 2004 279: 46242-46252. 2004. 14 57 Basavappa, S., Vulapalli S.R., Zhang, H., Yule, D.I. , Coon, S. and Sundaram U. Chloride channels in the small intestinal cell line IEC-18. J. Cell Physiol. 202(1):21-31. 2005. 58. Tsaneva-Atanasova, K. Yule, D.I. and Sneyd, J. Synchronisation of calcium oscillations in a pancreatic acinus. Biophys J. 88(3):1535-51. 2005 59. Mignen, O., Thompson, J.L., Yule, D.I and Shutleworth, T.J. Agonist activation of ARC channels in parotid and pancreatic acinar cells. J.Physiol. 564:791-801. 2005. 60. Chey, Y Warner, JD, Yule, D.I., and Giovannucci, D.R. Spatiotemporal analysis of exocytosis in mouse parotid acinar cells. American Journal of Physiology (Cell Physiology). 289(5):C1209-19. 2005. 61. Sneyd, J., Tsaneva-Atanasova, K., Reznikov, V., Bai Y., Sanderson, M. and Yule , D.I. Method for determining the dependence of calcium oscillations on inositol trisphosphate oscillations. Proc. Nat. Acad. Sci. (USA). 103.(6) 1675-1680. 2006. 62. Khan, M.T., Wagner,L.E. Yule, D.I., Bhanumathy, C., and Joseph, S.K. Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. J. Biol. Chem. Epub as doi:10.1074/jbc.M509262200. 63. Won, J-H and Yule, D.I. Measurement of Ca2+ Signaling Dynamics in Exocrine Cells with Total Internal Reflection Microscopy. Am J Physiol Gastrointest Liver Physiol. 2006 Feb 16; Epub PMID: 16484681. 64. Wagner, L.E. Betzenhauser, M. and Yule, D.I. ATP binding to a unique site in the type-1 S2- Inositol 1,4,5trisphosphate receptor defines susceptibility to phosphorylation by protein kinase A. J. Biol.Chem. 281. 17410-17419. 2006. 65. Brown, D.A and Yule, D.I. Protein kinase C regulation of P2X3 receptors is unlikely to involve direct receptor phosphorylation. BBA. 1773(2):166-75. 2007. 66. Gin E, Crampin, E, Brown D.A, Shuttleworth, T, Yule D.I., and Sneyd, JA. Mathematical model of fluid secretion from a parotid acinar cell. J. Theoretical Biology. 248(1):64-80. 2007. 67. Won, J-H, Cottrell, W.J, Foster, T.E, and Yule, D.I. Ca2+ Release dynamics in parotid and pancreatic exocrine acinar cells evoked by spatially limited flash photolysis. Am. J. Physiology. 293: G1166G1177. 2007. 68. Schug, Z., da Fonseca, P.C.A, Buanamathy, C.D, Wagner, L., Zhang, X., Bailey, B., Morris, E., Yule, D.I. and Joseph, S. A Molecular characterization of the Inositol 1,4,5-trisphosphate receptor pore forming segment. J. Biol.Chem. 283(5):2939-48. 2008. 69. Wagner, L.E. Joseph. SK and Yule D.I. Regulation of Single Inositol 1,4,5-Trisphosphate Receptor Channel Activity by Protein Kinase A phosphorylation. J. Physiol. 2008 Aug 1;586 (Pt 15):3577-96. 2008. 70. Betzenhauser, M. Wagner, L.E., Mikoshiba, K and Yule, D.I. ATP modulation of Ca2+ release by type-2 and type-3 InsP3R: differing ATP sensitivity and mechanism of regulation. J. Biol Chem. 283(31):21579-87. 2008. 72. Park, H-S, Betzenhauser, M.J., Won, J-H, Chen, J and Yule, D.I . The Type-2 InsP3 Receptor Determines the Sensitivity of InsP3-induced Ca2+ Release to ATP in Pancreatic Acinar Cells. J Biol Chem. 283(38):2608126088. 2008.73. 73. J. D. Warner, C. G. Peters, R. Saunders, J-H Won, M.J. Betzenhauser, W.T. Gunning III, D. I. Yule & D. R. Giovannucci. Form and Function in Organotypic Slices of the Adult Mouse Parotid Gland. Am J Physiol Gastrointest Liver Physiol. 295(3):G629-40. 2008. 15 74. Park, KM, Yule, DI and Bowers WJ. Tumor necrosis factor-alpha potentiates intraneuronal Ca2+ signaling via regulation of the inositol 1,4,5-trisphosphate receptor. J.Biol Chem. 283. 33069-33079. 2008. 75. M.J Betzenhauser, L. E. Wagner II, J-H Won and D. I. Yule. Studying isoform-specific inositol 1,4,5trisphosphate receptor function and regulation. Methods. 46 (3) 177-182. 2008. 76. Gin, E., Falcke, M., Wagner, L.E., Yule, D.I. Sneyd, J. Markov Chain Monte Carlo fitting of single-channel data from inositol trisphosphate receptors. Journal of Theoretical Biology. 257. 460-474. 2009. 77. Gin, E., Falcke, M., Wagner, L.E., Yule, D.I., Sneyd. J. A kinetic model of the inositol trisphosphate receptor based on single-channel data. Biophysical Journal. 96. (10) 4053-4062. 2009. 78. Betzenhauser, MJ; Wagner LE, Park HS and Yule D.I. ATP Regulation of Type-1 Inositol trisphosphate Receptor activity does not require Walker A-type motifs. J. Biol. Chem. 284. 16156-16163. 2009. 79. Betzenhauser, MJ., Fike, JL., Wagner, LE., and Yule, DI. Protein kinase A increases type-2 inositol (1,4,5)trisphosphate receptor activity by phosphorylation of serine 937. J Biol Chem. 2009 Sep 11;284(37):25116-25 80. Park KM., Yule DI., Bowers, WJ. TNF-{alpha} mediated regulation of the inositol 1,4,5 triphosphate receptor promoter. J Biol. Chem. 2009.284(40) 27557-66. 81. Park KM., Yule DI., Bowers, WJ. Impaired TNF-alpha control of IP3R-mediated Ca2+ release in Alzheimer's disease mouse neurons. Cell Signal. 2010. 22(3) 519-26. 82. Brown DA and Yule DI., Protein kinase A regulation of P2X(4) receptors: requirement for a specific motif in the Cterminus. Biochim. Biophys. Acta. 2010. 1803(2) 275-287. Chapters, Reviews and Symposium Contributions. 1. Williams, J.A. and Yule, D.I. Stimulus-secretion coupling in rat pancreatic acinar cells. In Pancreas: Biology, Pathobiology and Disease. Raven Press. New York. Ed. Go, W., et al. 2. Yule, D.I. and Williams, J.A. Stimulus-secretion coupling in the pancreatic acinus. In Physiology of the Gastrointestinal tract. Raven press. Ed. Johnson. L.R. Ch 39. pp1447-1471. 3. Palmer, R.K., Yule, D.I., McEwen, E.L. Williams, J.A., Fisher, S.K. Intra- and Intercellular calcium signaling in human neuroepithelioma cells. J. Lipid Mediators and Cell Signaling, 14(1-3):169-74, 1996 4. Williams, J.A., Groblewski, G.E., Ohnishi, H. and Yule, D.I. Stimulus-secretion coupling of pancreatic digestive enzyme secretion. Digestion. 58. Suppl 1:42-5, 1997. 5. Giovannucci DR, Sneyd J, Groblewski GE, Yule D.I. Modulation of InsP3 receptor properties by phosphorylation: targeting of PKA to InsP3 receptors shapes oscillatory calcium signals in pancreatic acinar cells. J Korean Med. Sci. Aug;15 Suppl:S55-6. 2000. 6. Yule, D.I. Subtype specific regulation of Inositol 1,4,5,-trisphosphate receptors: controlling calcium signals in time and space. J. General Physiol. 117(5) 431-433.2001. 16 7. Yule D.I., Straub S.V., Bruce J.I.E. Modulation of Ca2+ oscillations by phosphorylation of inositol 1,4,5 trisphosphate receptors. Biochem. Soc. Trans. 31 (5) 954-957. 2003. 8. Bruce J.I.E. Straub S.V., Yule D.I. Crosstalk between cAMP and Ca2+ signalling in non-excitable cells Cell Calcium. 34. 431-444. 2003. 9. Gunter, T.E., Yule, D.I., Gunter, K.K. Eliseev, R.A. and Salter, J.D. Calcium and mitochondria. FEBS Lett.; 567(1):96-102. 2004. 10. Straub SV, Wagner, L., Bruce, J.I.E. Yule D.I. Crosstalk between calcium and cAMP signaling pathways. Biological Research. 37(4):593-602.2004. 11. Melvin, J.E, Yule, D.I., Shuttleworth, T.J. and Begenesich, T. Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Ann. Rev Physiol.67:445-469. 2005. 12. Williams J.A. and Yule, D.I. Stimulus-Secretion Coupling in the Pancreatic Acinus. In Physiology of the Gastrointestinal Tract. Ed L.R. Johnson. 5th Edition. Pages 1337-1369. 2006. 13. Yule DI., Betzenhauser MB., and Joseph SK. Linking structure to function: Recent lessons from inositol 1,4,5trisphosphate receptor mutagenesis. Cell Calcium. 2010. 47(6) 469-476. 14. Yule DI. Pancreatic Acinar Cells: Molecular insight from studies of signal-transduction using transgenic animals. International Journal of Biochemistry and Cell Biology. 2010. In press. 17
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