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Joshua Jay Singer PhD

TitleProfessor Emeritus
InstitutionUMass Chan Medical School
DepartmentMicrobiology
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-6694
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentMicrobiology


    Collapse Biography 
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    Massachusetts Institute of Technology, Cambridge, MA, United StatesSB SM EEElectrical Engineering
    Harvard University, Cambridge, MA, United StatesPHDPhysiology

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    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+.



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    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. PMID: 17483243.
      Citations: 6     Fields:    Translation:AnimalsCells
    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. PMID: 15337821.
      Citations: 14     Fields:    Translation:AnimalsCells
    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. PMID: 15110142.
      Citations: 9     Fields:    Translation:AnimalsCells
    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. PMID: 12372805.
      Citations: 29     Fields:    Translation:AnimalsCells
    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. PMID: 12409285.
      Citations: 11     Fields:    Translation:Cells
    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. PMID: 11983921.
      Citations: 30     Fields:    Translation:Animals
    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. PMID: 11865021.
      Citations: 36     Fields:    Translation:Animals
    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 01; 534(Pt 1):59-70. PMID: 11432992.
      Citations:    
    9. Kirber MT, Guerrero-Hern?ndez 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 01; 524 Pt 1:3-17. PMID: 10747180.
      Citations:    
    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. PMID: 10498675.
      Citations:    
    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. PMID: 9271232.
      Citations: 35     Fields:    Translation:AnimalsCells
    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. PMID: 9032690.
      Citations: 7     Fields:    Translation:AnimalsCells
    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. PMID: 7602529.
      Citations: 13     Fields:    Translation:Animals
    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. PMID: 7784455.
      Citations: 11     Fields:    Translation:Animals
    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. PMID: 7807055.
      Citations:    
    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. PMID: 7807054.
      Citations:    
    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. PMID: 8195783.
      Citations: 14     Fields:    Translation:Animals
    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. PMID: 8136116.
      Citations: 23     Fields:    Translation:AnimalsCells
    19. Hisada T, Walsh JV, Singer JJ. Stretch-inactivated cationic channels in single smooth muscle cells. Pflugers Arch. 1993 Jan; 422(4):393-6. PMID: 7679792.
      Citations: 4     Fields:    Translation:Animals
    20. 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. PMID: 7679793.
      Citations: 2     Fields:    Translation:Animals
    21. 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. PMID: 1476168.
      Citations: 5     Fields:    Translation:Animals
    22. 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 03; 297(1-2):24-8. PMID: 1551431.
      Citations: 48     Fields:    Translation:AnimalsCells
    23. 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. PMID: 1710335.
      Citations: 8     Fields:    Translation:Animals
    24. Ordway RW, Singer JJ, Walsh JV. Direct regulation of ion channels by fatty acids. Trends Neurosci. 1991 Mar; 14(3):96-100. PMID: 1709540.
      Citations: 83     Fields:    Translation:Animals
    25. 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. PMID: 1707158.
      Citations: 13     Fields:    Translation:Animals
    26. 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. PMID: 2177185.
      Citations: 1     Fields:    Translation:Animals
    27. 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. PMID: 2159241.
      Citations: 9     Fields:    Translation:AnimalsCells
    28. 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. PMID: 2408067.
      Citations:    Fields:    Translation:HumansCells
    29. Ordway RW, Walsh JV, Singer JJ. Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science. 1989 Jun 09; 244(4909):1176-9. PMID: 2471269.
      Citations: 64     Fields:    Translation:Animals
    30. 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. PMID: 2472601.
      Citations: 3     Fields:    Translation:Animals
    31. 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. PMID: 2459658.
      Citations: 53     Fields:    Translation:Animals
    32. 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. PMID: 2453389.
      Citations: 25     Fields:    Translation:Animals
    33. Sims SM, Singer JJ, Walsh JV. Antagonistic adrenergic-muscarinic regulation of M current in smooth muscle cells. Science. 1988 Jan 08; 239(4836):190-3. PMID: 2827305.
      Citations: 19     Fields:    Translation:Animals
    34. 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. PMID: 2455466.
      Citations: 2     Fields:    Translation:Animals
    35. Clapp LH, Vivaudou MB, Walsh JV, Singer JJ. Acetylcholine increases voltage-activated Ca2+ current in freshly dissociated smooth muscle cells. Proc Natl Acad Sci U S A. 1987 Apr; 84(7):2092-6. PMID: 2436224.
      Citations: 24     Fields:    Translation:Animals
    36. Singer JJ, Walsh JV. Characterization of calcium-activated potassium channels in single smooth muscle cells using the patch-clamp technique. Pflugers Arch. 1987 Feb; 408(2):98-111. PMID: 2436143.
      Citations: 64     Fields:    Translation:Animals
    37. Walsh JV, Singer JJ. Identification and characterization of major ionic currents in isolated smooth muscle cells using the voltage-clamp technique. Pflugers Arch. 1987 Feb; 408(2):83-97. PMID: 2436142.
      Citations: 25     Fields:    Translation:Animals
    38. Sims SM, Walsh JV, Singer JJ. Substance P and acetylcholine both suppress the same K+ current in dissociated smooth muscle cells. Am J Physiol. 1986 Oct; 251(4 Pt 1):C580-7. PMID: 2429556.
      Citations: 11     Fields:    Translation:Animals
    39. Lassignal NL, Singer JJ, Walsh JV. Multiple neuropeptides exert a direct effect on the same isolated single smooth muscle cell. Am J Physiol. 1986 May; 250(5 Pt 1):C792-8. PMID: 2422949.
      Citations: 19     Fields:    Translation:Animals
    40. Singer JJ, Walsh JV. Large-conductance Ca2+-activated K+ channels in freshly dissociated smooth muscle cells. Membr Biochem. 1986; 6(2):83-110. PMID: 2427921.
      Citations: 10     Fields:    Translation:Animals
    41. Sims SM, Singer JJ, Walsh JV. Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad. J Physiol. 1985 Oct; 367:503-29. PMID: 2414443.
      Citations: 27     Fields:    Translation:Animals
    42. Kirber MT, Singer JJ, Walsh JV, Fuller MS, Peura RA. Possible forms for dwell-time histograms from single-channel current records. J Theor Biol. 1985 Sep 07; 116(1):111-26. PMID: 2413315.
      Citations: 2     Fields:    
    43. Singer JJ, Walsh JV. Large conductance ca-activated k channels in smooth muscle cell membrane: reduction in unitary currents due to internal na ions. Biophys J. 1984 Jan; 45(1):68-70. PMID: 19431570.
      Citations: 27     Fields:    
    44. Walsh JV, Singer JJ. Ca++-activated K+ channels in vertebrate smooth muscle cells. Cell Calcium. 1983 Dec; 4(5-6):321-30. PMID: 6322998.
      Citations: 16     Fields:    Translation:Animals
    45. Walsh JV, Singer JJ. Voltage clamp of single freshly dissociated smooth muscle cells: current-voltage relationships for three currents. Pflugers Arch. 1981 May; 390(2):207-10. PMID: 6787566.
      Citations: 37     Fields:    Translation:AnimalsCells
    46. Walsh JV, Singer JJ. Penetration-induced hyperpolarization as evidence for Ca2+ activation of K+ conductance in isolated smooth muscle cells. Am J Physiol. 1980 Nov; 239(5):C182-9. PMID: 6776821.
      Citations: 16     Fields:    Translation:Animals
    47. Singer JJ, Walsh JV. Rectifying properties of the membrane of single freshly isolated smooth muscle cells. Am J Physiol. 1980 Nov; 239(5):C175-81. PMID: 6776820.
      Citations: 6     Fields:    Translation:AnimalsCells
    48. Walsh JV, Singer JJ. Calcium action potentials in single freshly isolated smooth muscle cells. Am J Physiol. 1980 Nov; 239(5):C162-74. PMID: 6776819.
      Citations: 21     Fields:    Translation:Animals
    49. Singer JJ, Walsh JV. Passive properties of the membrane of single freshly isolated smooth muscle cells. Am J Physiol. 1980 Nov; 239(5):C153-61. PMID: 6776818.
      Citations: 22     Fields:    Translation:Animals
    50. Fay FS, Singer JJ. Characteristics of response of isolated smooth muscle cells to cholinergic drugs. Am J Physiol. 1977 Mar; 232(3):C144-54. PMID: 402821.
      Citations:    
    51. Singer JJ, Fay FS. Detection of contraction of isolated smooth muscle cells in suspension. Am J Physiol. 1977 Mar; 232(3):C138-43. PMID: 402820.
      Citations:    
    52. Houk JC, Singer JJ, Henneman E. Adequate stimulus for tendon organs with observations on mechanics of ankle joint. J Neurophysiol. 1971 Nov; 34(6):1051-65. PMID: 5115910.
      Citations:    
    53. Houk JC, Singer JJ, Goldman MR. An evaluation of length and force feedback to soleus muscles of decerebrate cats. J Neurophysiol. 1970 Nov; 33(6):784-811. PMID: 4249581.
      Citations:    
    54. Goldberg AL, Singer JJ. Evidence for a role of cyclic AMP in neuromuscular transmission. Proc Natl Acad Sci U S A. 1969 Sep; 64(1):134-41. PMID: 4312746.
      Citations:    
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