Joshua Jay Singer PhD
Title Professor
Institution University of Massachusetts Medical School
Department Microbiology & Physiological Systems
Address University of Massachusetts Medical School
55 Lake Ave North
Worcester MA 01655
Telephone 508/856-6694
Email
Other Positions
Institution UMMS - School of Medicine
Department Biochemistry & Molecular Pharmacology

Institution UMMS - Graduate School of Biomedical Sciences
Department Neuroscience
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 mechanisms involved in membrane electrical events and the relationship of these events to biochemical and physiological processes. Studies are carried out using mammalian and amphibian single smooth muscle cells and other cell types as well as various expression systems including Xenopus oocytes. We are using voltage-clamp techniques for measuring macroscopic membrane currents, the patch-clamp technique for measuring currents passing through single ion channels, Ca2+ imaging techniques for examining the temporal and spatial distribution of cellular Ca2+, and molecular biological techniques for studying cloned channels, identifying new channels, and determining various functional domains of channel proteins. We have been examining the voltage, chemical, mechanical, and ionic control of membrane channels; the mechanism of action of neurotransmitters, peptides, drugs and other agents; and the role of these in cellular function. Specifically, we have recently been interested in the direct effects of fatty acids, sphingosine, steroids, and other biologically active lipids on smooth muscle and neuron ion channel activity; the role of mechanically-gated ion channels in the control of stretch-induced contraction of smooth muscle; various Ca2+ permeable nonselective cation channels activated by caffeine, NMDA and ATP; and the relationship between ion channel gating and changes in the local concentration of cellular Ca2+.

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.
  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, 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
 
16. 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
 
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
 
For assistance with using Profiles, please refer to the online tutorials at http://inside.umassmed.edu/is/profiles.aspx or contact the UMMS Help Desk at UMWHelpDesk@umassmed.edu or 508-856-8643.
 
Keyword
Last Name
Institution
    
 
 
 
Keywords   
Muscle, Smooth
Calcium Channels
Calcium
Fatty Acids
Potassium Channels
See all (153) keywords
Co-Authors  
Fogarty, Kevin
Lifshitz, Lawrence
Tuft, Richard
Walsh, John
See all (4) people
Physical Neighbors  
Poteete, Anthony
Akerley, Brian
Jenness, Duane
He, Feng
Wong, Sandy

UMMS Home

Intranet

This is an official Page/Publication of the University of Massachusetts Worcester Campus
Office of the Vice Provost for Research, 55 Lake Ave North, Worcester, Massachusetts 01655
Questions or Comments? Email: publicaffairs@umassmed.edu Phone: 508-856-1572