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    Joshua Jay Singer PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMicrobiology and Physiological Systems
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-6694
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Academic Background

        1966, S.B., S.M., E.E., Massachusetts Institute of Technology
        1970, Ph.D., Harvard University

        Ion channel behavior and cellular physiological and biochemical processes

        The aim of our research is to understand the molecular mechanismsinvolved in membrane electrical events and the relationship of theseevents to biochemical and physiological processes. Studies are carriedout using mammalian and amphibian single smooth muscle cells and othercell types as well as various expression systems including Xenopusoocytes. We are using voltage-clamp techniques for measuring macroscopicmembrane currents, the patch-clamp technique for measuring currentspassing through single ion channels, Ca2+imaging techniques for examining the temporal and spatial distribution ofcellular Ca2+, and molecular biologicaltechniques for studying cloned channels, identifying new channels, anddetermining various functional domains of channel proteins. We have beenexamining the voltage, chemical, mechanical, and ionic control of membranechannels; the mechanism of action of neurotransmitters, peptides, drugsand other agents; and the role of these in cellular function. Specifically, we have recently been interested in the direct effects offatty acids, sphingosine, steroids, and other biologically active lipidson smooth muscle and neuron ion channel activity; the role ofmechanically-gated ion channels in the control of stretch-inducedcontraction of smooth muscle; various Ca2+permeable nonselective cation channels activated by caffeine, NMDA andATP; and the relationship between ion channel gating and changes in thelocal concentration of cellular Ca2+.



        Bibliographic 
        selected publications
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        1. Zhang YA, Tuft RA, Lifshitz LM, Fogarty KE, Singer JJ, Zou H. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance. Am J Physiol Heart Circ Physiol. 2007 Oct; 293(4):H2448-61.
          View in: PubMed
        2. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Using total fluorescence increase (signal mass) to determine the Ca2+ current underlying localized Ca2+ events. J Gen Physiol. 2004 Sep; 124(3):259-72.
          View in: PubMed
        3. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Imaging calcium entering the cytosol through a single opening of plasma membrane ion channels: SCCaFTs--fundamental calcium events. Cell Calcium. 2004 Jun; 35(6):523-33.
          View in: PubMed
        4. Clarke AL, Petrou S, Walsh JV, Singer JJ. Modulation of BK(Ca) channel activity by fatty acids: structural requirements and mechanism of action. Am J Physiol Cell Physiol. 2002 Nov; 283(5):C1441-53.
          View in: PubMed
        5. Clarke AL, Petrou S, Walsh JV, Singer JJ. Site of action of fatty acids and other charged lipids on BKCa channels from arterial smooth muscle cells. Am J Physiol Cell Physiol. 2003 Mar; 284(3):C607-19.
          View in: PubMed
        6. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Visualization of Ca2+ entry through single stretch-activated cation channels. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):6404-9.
          View in: PubMed
        7. Dopico AM, Walsh JV, Singer JJ. Natural bile acids and synthetic analogues modulate large conductance Ca2+-activated K+ (BKCa) channel activity in smooth muscle cells. J Gen Physiol. 2002 Mar; 119(3):251-73.
          View in: PubMed
        8. Zou H, Ugur M, Drummond RM, Singer JJ. Coupling of a P2Z-like purinoceptor to a fatty acid-activated K(+) channel in toad gastric smooth muscle cells. J Physiol. 2001 Jul 1; 534(Pt 1):59-70.
          View in: PubMed
        9. Kirber MT, Guerrero-Hernández A, Bowman DS, Fogarty KE, Tuft RA, Singer JJ, Fay FS. Multiple pathways responsible for the stretch-induced increase in Ca2+ concentration in toad stomach smooth muscle cells. J Physiol. 2000 Apr 1; 524 Pt 1:3-17.
          View in: PubMed
        10. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Imaging Ca(2+) entering the cytoplasm through a single opening of a plasma membrane cation channel. J Gen Physiol. 1999 Oct; 114(4):575-88.
          View in: PubMed
        11. Petrou S, Ugur M, Drummond RM, Singer JJ, Walsh JV. P2X7 purinoceptor expression in Xenopus oocytes is not sufficient to produce a pore-forming P2Z-like phenotype. FEBS Lett. 1997 Jul 14; 411(2-3):339-45.
          View in: PubMed
        12. Ugur M, Drummond RM, Zou H, Sheng P, Singer JJ, Walsh JV. An ATP-gated cation channel with some P2Z-like characteristics in gastric smooth muscle cells of toad. J Physiol. 1997 Jan 15; 498 ( Pt 2):427-42.
          View in: PubMed
        13. Ordway RW, Petrou S, Kirber MT, Walsh JV, Singer JJ. Stretch activation of a toad smooth muscle K+ channel may be mediated by fatty acids. J Physiol. 1995 Apr 15; 484 ( Pt 2):331-7.
          View in: PubMed
        14. Petrou S, Ordway RW, Kirber MT, Dopico AM, Hamilton JA, Walsh JV, Singer JJ. Direct effects of fatty acids and other charged lipids on ion channel activity in smooth muscle cells. Prostaglandins Leukot Essent Fatty Acids. 1995 Feb-Mar; 52(2-3):173-8.
          View in: PubMed
        15. Guerrero A, Singer JJ, Fay FS. Simultaneous measurement of Ca2+ release and influx into smooth muscle cells in response to caffeine. A novel approach for calculating the fraction of current carried by calcium. J Gen Physiol. 1994 Aug; 104(2):395-422.
          View in: PubMed
        16. Guerrero A, Fay FS, Singer JJ. Caffeine activates a Ca(2+)-permeable, nonselective cation channel in smooth muscle cells. J Gen Physiol. 1994 Aug; 104(2):375-94.
          View in: PubMed
        17. Petrou S, Ordway RW, Hamilton JA, Walsh JV, Singer JJ. Structural requirements for charged lipid molecules to directly increase or suppress K+ channel activity in smooth muscle cells. Effects of fatty acids, lysophosphatidate, acyl coenzyme A and sphingosine. J Gen Physiol. 1994 Mar; 103(3):471-86.
          View in: PubMed
        18. Dopico AM, Kirber MT, Singer JJ, Walsh JV. Membrane stretch directly activates large conductance Ca(2+)-activated K+ channels in mesenteric artery smooth muscle cells. Am J Hypertens. 1994 Jan; 7(1):82-9.
          View in: PubMed
        19. Petrou S, Ordway RW, Singer JJ, Walsh JV. A putative fatty acid-binding domain of the NMDA receptor. Trends Biochem Sci. 1993 Feb; 18(2):41-2.
          View in: PubMed
        20. Hisada T, Walsh JV, Singer JJ. Stretch-inactivated cationic channels in single smooth muscle cells. Pflugers Arch. 1993 Jan; 422(4):393-6.
          View in: PubMed
        21. Hisada T, Singer JJ, Walsh JV. Aluminofluoride activates hyperpolarization- and stretch-activated cationic channels in single smooth muscle cells. Pflugers Arch. 1993 Jan; 422(4):397-400.
          View in: PubMed
        22. Clapp LH, Sims SM, Singer JJ, Walsh JV. Role for diacylglycerol in mediating the actions of ACh on M-current in gastric smooth muscle cells. Am J Physiol. 1992 Dec; 263(6 Pt 1):C1274-81.
          View in: PubMed
        23. Kirber MT, Ordway RW, Clapp LH, Walsh JV, Singer JJ. Both membrane stretch and fatty acids directly activate large conductance Ca(2+)-activated K+ channels in vascular smooth muscle cells. FEBS Lett. 1992 Feb 3; 297(1-2):24-8.
          View in: PubMed
        24. Ordway RW, Singer JJ, Walsh JV. Direct regulation of ion channels by fatty acids. Trends Neurosci. 1991 Mar; 14(3):96-100.
          View in: PubMed
        25. Vivaudou MB, Singer JJ, Walsh JV. Multiple types of Ca2+ channels in visceral smooth muscle cells. Pflugers Arch. 1991 Mar; 418(1-2):144-52.
          View in: PubMed
        26. Hisada T, Ordway RW, Kirber MT, Singer JJ, Walsh JV. Hyperpolarization-activated cationic channels in smooth muscle cells are stretch sensitive. Pflugers Arch. 1991 Jan; 417(5):493-9.
          View in: PubMed
        27. Sims SM, Clapp LH, Walsh JV, Singer JJ. Dual regulation of M current in gastric smooth muscle cells: beta-adrenergic-muscarinic antagonism. Pflugers Arch. 1990 Nov; 417(3):291-302.
          View in: PubMed
        28. Sims SM, Vivaudou MB, Hillemeier C, Biancani P, Walsh JV, Singer JJ. Membrane currents and cholinergic regulation of K+ current in esophageal smooth muscle cells. Am J Physiol. 1990 May; 258(5 Pt 1):G794-802.
          View in: PubMed
        29. Kirber MT, Ordway RW, Clapp LH, Sims SM, Walsh JV, Singer JJ. Voltage, ligand, and mechanically gated channels in freshly dissociated single smooth muscle cells. Prog Clin Biol Res. 1990; 334:123-43.
          View in: PubMed
        30. Ordway RW, Walsh JV, Singer JJ. Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science. 1989 Jun 9; 244(4909):1176-9.
          View in: PubMed
        31. Becker PL, Singer JJ, Walsh JV, Fay FS. Regulation of calcium concentration in voltage-clamped smooth muscle cells. Science. 1989 Apr 14; 244(4901):211-4.
          View in: PubMed
        32. Clapp LH, Vivaudou MB, Singer JJ, Walsh JV. Substance P, like acetylcholine, augments one type of Ca2+ current in isolated smooth muscle cells. Pflugers Arch. 1989 Mar; 413(5):565-7.
          View in: PubMed
        33. Kirber MT, Walsh JV, Singer JJ. Stretch-activated ion channels in smooth muscle: a mechanism for the initiation of stretch-induced contraction. Pflugers Arch. 1988 Sep; 412(4):339-45.
          View in: PubMed
        34. Vivaudou MB, Clapp LH, Walsh JV, Singer JJ. Regulation of one type of Ca2+ current in smooth muscle cells by diacylglycerol and acetylcholine. FASEB J. 1988 Jun; 2(9):2497-504.
          View in: PubMed
        35. Sims SM, Singer JJ, Walsh JV. Antagonistic adrenergic-muscarinic regulation of M current in smooth muscle cells. Science. 1988 Jan 8; 239(4836):190-3.
          View in: PubMed
        36. Sims SM, Vivaudou MB, Clapp LH, Lassignal NL, Walsh JV, Singer JJ. Neurotransmitter regulation of ionic channels in freshly dissociated smooth muscle cells. Ann N Y Acad Sci. 1988; 527:346-59.
          View in: PubMed
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