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Peter Shrager

TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentNeurobiology and Anatomy
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 603
Rochester NY 14642
Other Positions
TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentPharmacology and Physiology

 
 Awards And Honors
      Phi Beta Kappa
      Tau Beta Pi (engineering)
      Eta Kappa Nu (electrical engineering)
      NIH Predoctoral Fellowship
      NIH Postdoctoral Fellowship
      NSF Postdoctoral Fellowship
      NIH Research Career Development Award
      Mellon Fellow
      First-Year Teaching Award
      Graduate Student Society Faculty Teaching Award
      Fenn Mentor Award
 
 Overview
The focus of this laboratory is on the interaction between neurons and glial cells, particularly myelinating glia. There are two primary areas of interest. Myelinated axons are not uniform, but rather consist of highly discrete domains, populated by unique proteins that confer specialized functional properties. The axon initial segment contains a high density of voltage-dependent sodium channels, as well as an associated set of cytoskeletal, adhesion, and matrix components, all of which allow this region to be the site of integration of synaptic inputs, resulting in the initiation of the action potential. Nodes of Ranvier have a similar composition, but reach that structure through a very different developmental mechanism. Nodes and adjacent paranodes and juxtaparanodes, along with compact myelin in the internodes, allow rapid, reliable, and efficient conduction of impulses. Our laboratory studies the molecular interactions between components of axons and Schwann cells (PNS) or oligodendroglia (CNS) that result in this unique structure. A wide variety of techniques, both molecular and electrophysiological are employed. A second major area is in recovery from spinal cord injury, and other traumatic diseases of the CNS. While axon regeneration can be robust in the PNS, it is markedly limited in the CNS. Among the mechanisms responsible, it has been demonstrated that remaining myelin at the injury site contains several proteins that are inhibitory to neurite outgrowth. This inhibition is mediated by receptors present on neurons that form a complex capable of initiating an intracellular signaling cascade. Using the optic nerve as a well-defined tract of CNS axons, and a series of mutant mice with the relevant proteins genetically deleted, a mechanism is sought through which regeneration can be improved. A question arose in the course of this work. Since these inhibitors and receptors are not likely to have evolved for this purpose, do they mediate other functions in the CNS? It has subsequently been shown that both the inhibitory proteins and their receptors are expressed by neurons at excitatory synapses. Further, in collaboration with Roman Giger, this laboratory has been investigating the role of this system in synaptic plasticity. Of particular interest, long term potentiation and depression, thought to be electrophysiological correlates of memory formation in the hippocampus, are regulated by this growth-inhibitory system. While this is studied for its intrinsic value in neurobiology, it is also relevant in spinal cord injury, where plasticity in remaining neurons is thought to play an important role in recovery of function.

Recent publications (2010-2012)

Raiker, S.J., Lee, H., Duan, Y., Koelzer, K.T., Shrager, P. and Giger, R.J. 2010 Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity. Journal of Neuroscience 30:12432-12445.

Winters, J., Lenk, G., Giger-Mateeva, V., Shrager, P., Meisler, M. and Giger, R..J. 2011 Congenital CNS hypomyelination and reduced number of mature oligodendrocytes in the Fig4 null mouse. Journal of Neuroscience, in review.

Einheber, S., Maurel, P., Meng, X., Rubin, M., Lam, I., Mohandas, N., An, X., Shrager, P., Kissil, J. and Salzer, J. 2011 The 4.1B cytoskeletal protein is required for the normal domain organization of myelinated axons. Glia (online) 10-26-2012 DOI: 10:1002/glia22430.

 
 Selected Publications
List All   |   Timeline
  1. Einheber S, Meng X, Rubin M, Lam I, Mohandas N, An X, Shrager P, Kissil J, Maurel P, Salzer JL. The 4.1B cytoskeletal protein regulates the domain organization and sheath thickness of myelinated axons. Glia. 2013 Feb; 61(2):240-53.
    View in: PubMed
  2. Winters JJ, Ferguson CJ, Lenk GM, Giger-Mateeva VI, Shrager P, Meisler MH, Giger RJ. Congenital CNS hypomyelination in the Fig4 null mouse is rescued by neuronal expression of the PI(3,5)P(2) phosphatase Fig4. J Neurosci. 2011 Nov 30; 31(48):17736-51.
    View in: PubMed
  3. Raiker SJ, Lee H, Baldwin KT, Duan Y, Shrager P, Giger RJ. Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity. J Neurosci. 2010 Sep 15; 30(37):12432-45.
    View in: PubMed
  4. Feinberg K, Eshed-Eisenbach Y, Frechter S, Amor V, Salomon D, Sabanay H, Dupree JL, Grumet M, Brophy PJ, Shrager P, Peles E. A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier. Neuron. 2010 Feb 25; 65(4):490-502.
    View in: PubMed
  5. Lee H, Raiker SJ, Venkatesh K, Geary R, Robak LA, Zhang Y, Yeh HH, Shrager P, Giger RJ. Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J Neurosci. 2008 Mar 12; 28(11):2753-65.
    View in: PubMed
  6. Hedstrom KL, Xu X, Ogawa Y, Frischknecht R, Seidenbecher CI, Shrager P, Rasband MN. Neurofascin assembles a specialized extracellular matrix at the axon initial segment. J Cell Biol. 2007 Aug 27; 178(5):875-86.
    View in: PubMed
  7. Schafer DP, Custer AW, Shrager P, Rasband MN. Early events in node of Ranvier formation during myelination and remyelination in the PNS. Neuron Glia Biol. 2006 May; 2(2):69-79.
    View in: PubMed
  8. Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, Xu X, Esper RM, Loeb JA, Shrager P, Chao MV, Falls DL, Role L, Salzer JL. Neuregulin-1 type III determines the ensheathment fate of axons. Neuron. 2005 Sep 1; 47(5):681-94.
    View in: PubMed
  9. Xu X, Shrager P. Dependence of axon initial segment formation on Na+ channel expression. J Neurosci Res. 2005 Feb 15; 79(4):428-41.
    View in: PubMed
  10. Chen C, Westenbroek RE, Xu X, Edwards CA, Sorenson DR, Chen Y, McEwen DP, O'Malley HA, Bharucha V, Meadows LS, Knudsen GA, Vilaythong A, Noebels JL, Saunders TL, Scheuer T, Shrager P, Catterall WA, Isom LL. Mice lacking sodium channel beta1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture. J Neurosci. 2004 Apr 21; 24(16):4030-42.
    View in: PubMed
  11. Custer AW, Kazarinova-Noyes K, Sakurai T, Xu X, Simon W, Grumet M, Shrager P. The role of the ankyrin-binding protein NrCAM in node of Ranvier formation. J Neurosci. 2003 Nov 5; 23(31):10032-9.
    View in: PubMed
  12. Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, Xu X, Chiu SY, Shrager P, Furley AJ, Peles E. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol. 2003 Sep 15; 162(6):1149-60.
    View in: PubMed
  13. Chen C, Bharucha V, Chen Y, Westenbroek RE, Brown A, Malhotra JD, Jones D, Avery C, Gillespie PJ, Kazen-Gillespie KA, Kazarinova-Noyes K, Shrager P, Saunders TL, Macdonald RL, Ransom BR, Scheuer T, Catterall WA, Isom LL. Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2-subunits. Proc Natl Acad Sci U S A. 2002 Dec 24; 99(26):17072-7.
    View in: PubMed
  14. Kazarinova-Noyes K, Shrager P. Molecular constituents of the node of Ranvier. Mol Neurobiol. 2002 Oct-Dec; 26(2-3):167-82.
    View in: PubMed
  15. Kazarinova-Noyes K, Malhotra JD, McEwen DP, Mattei LN, Berglund EO, Ranscht B, Levinson SR, Schachner M, Shrager P, Isom LL, Xiao ZC. Contactin associates with Na+ channels and increases their functional expression. J Neurosci. 2001 Oct 1; 21(19):7517-25.
    View in: PubMed
  16. Harroch S, Palmeri M, Rosenbluth J, Custer A, Okigaki M, Shrager P, Blum M, Buxbaum JD, Schlessinger J. No obvious abnormality in mice deficient in receptor protein tyrosine phosphatase beta. Mol Cell Biol. 2000 Oct; 20(20):7706-15.
    View in: PubMed
  17. Rasband MN, Shrager P. Ion channel sequestration in central nervous system axons. J Physiol. 2000 May 15; 525 Pt 1:63-73.
    View in: PubMed
  18. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron. 1999 Dec; 24(4):1037-47.
    View in: PubMed
  19. Rasband MN, Peles E, Trimmer JS, Levinson SR, Lux SE, Shrager P. Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS. J Neurosci. 1999 Sep 1; 19(17):7516-28.
    View in: PubMed
  20. Weber P, Bartsch U, Rasband MN, Czaniera R, Lang Y, Bluethmann H, Margolis RU, Levinson SR, Shrager P, Montag D, Schachner M. Mice deficient for tenascin-R display alterations of the extracellular matrix and decreased axonal conduction velocities in the CNS. J Neurosci. 1999 Jun 1; 19(11):4245-62.
    View in: PubMed
  21. Rasband MN, Trimmer JS, Peles E, Levinson SR, Shrager P. K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J Neurocytol. 1999 Apr-May; 28(4-5):319-31.
    View in: PubMed
  22. Vabnick I, Trimmer JS, Schwarz TL, Levinson SR, Risal D, Shrager P. Dynamic potassium channel distributions during axonal development prevent aberrant firing patterns. J Neurosci. 1999 Jan 15; 19(2):747-58.
    View in: PubMed
  23. Vabnick I, Shrager P. Ion channel redistribution and function during development of the myelinated axon. J Neurobiol. 1998 Oct; 37(1):80-96.
    View in: PubMed
  24. Novakovic SD, Levinson SR, Schachner M, Shrager P. Disruption and reorganization of sodium channels in experimental allergic neuritis. Muscle Nerve. 1998 Aug; 21(8):1019-32.
    View in: PubMed
  25. Shrager P, Custer AW, Kazarinova K, Rasband MN, Mattson D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J Neurophysiol. 1998 Feb; 79(2):529-36.
    View in: PubMed
  26. Rasband MN, Trimmer JS, Schwarz TL, Levinson SR, Ellisman MH, Schachner M, Shrager P. Potassium channel distribution, clustering, and function in remyelinating rat axons. J Neurosci. 1998 Jan 1; 18(1):36-47.
    View in: PubMed
  27. Vabnick I, Messing A, Chiu SY, Levinson SR, Schachner M, Roder J, Li C, Novakovic S, Shrager P. Sodium channel distribution in axons of hypomyelinated and MAG null mutant mice. J Neurosci Res. 1997 Oct 15; 50(2):321-36.
    View in: PubMed
  28. Vabnick I, Novakovic SD, Levinson SR, Schachner M, Shrager P. The clustering of axonal sodium channels during development of the peripheral nervous system. J Neurosci. 1996 Aug 15; 16(16):4914-22.
    View in: PubMed
  29. England JD, Levinson SR, Shrager P. Immunocytochemical investigations of sodium channels along nodal and internodal portions of demyelinated axons. Microsc Res Tech. 1996 Aug 1; 34(5):445-51.
    View in: PubMed
  30. Novakovic SD, Deerinck TJ, Levinson SR, Shrager P, Ellisman MH. Clusters of axonal Na+ channels adjacent to remyelinating Schwann cells. J Neurocytol. 1996 Jun; 25(6):403-12.
    View in: PubMed
  31. Tzoumaka EE, Novakovic SD, Levinson SR, Shrager P. Na+ channel aggregation in remyelinating mouse sciatic axons following transection. Glia. 1995 Oct; 15(2):188-94.
    View in: PubMed
  32. Shrager P, Novakovic SD. Control of myelination, axonal growth, and synapse formation in spinal cord explants by ion channels and electrical activity. Brain Res Dev Brain Res. 1995 Aug 28; 88(1):68-78.
    View in: PubMed
  33. Dugandzija-Novakovic S, Koszowski AG, Levinson SR, Shrager P. Clustering of Na+ channels and node of Ranvier formation in remyelinating axons. J Neurosci. 1995 Jan; 15(1 Pt 2):492-503.
    View in: PubMed
  34. Dugandzija-Novakovic S, Shrager P. Survival, development, and electrical activity of central nervous system myelinated axons exposed to tumor necrosis factor in vitro. J Neurosci Res. 1995 Jan 1; 40(1):117-26.
    View in: PubMed
  35. Wu JV, Shrager P. Resolving three types of chloride channels in demyelinated Xenopus axons. J Neurosci Res. 1994 Aug 15; 38(6):613-20.
    View in: PubMed
  36. Wu JV, Rubinstein CT, Shrager P. Single channel characterization of multiple types of potassium channels in demyelinated Xenopus axons. J Neurosci. 1993 Dec; 13(12):5153-63.
    View in: PubMed
  37. Shrager P. Axonal coding of action potentials in demyelinated nerve fibers. Brain Res. 1993 Aug 13; 619(1-2):278-90.
    View in: PubMed
  38. Shen L, Shrager P, Girsch SJ, Donaldson PJ, Peracchia C. Channel reconstitution in liposomes and planar bilayers with HPLC-purified MIP26 of bovine lens. J Membr Biol. 1991 Oct; 124(1):21-32.
    View in: PubMed
  39. Hines M, Shrager P. A computational test of the requirements for conduction in demyelinated axons. Restor Neurol Neurosci. 1991 Jan 1; 3(2):81-93.
    View in: PubMed
  40. Rubinstein CT, Shrager P. Remyelination of nerve fibers in the transected frog sciatic nerve. Brain Res. 1990 Aug 6; 524(2):303-12.
    View in: PubMed
  41. Shrager P, Rubinstein CT. Optical measurement of conduction in single demyelinated axons. J Gen Physiol. 1990 May; 95(5):867-89.
    View in: PubMed
  42. Shrager P. Sodium channels in single demyelinated mammalian axons. Brain Res. 1989 Mar 27; 483(1):149-54.
    View in: PubMed
  43. Shrager P. Ionic channels and signal conduction in single remyelinating frog nerve fibres. J Physiol. 1988 Oct; 404:695-712.
    View in: PubMed
  44. Shrager P. The distribution of sodium and potassium channels in single demyelinated axons of the frog. J Physiol. 1987 Nov; 392:587-602.
    View in: PubMed
  45. Shrager P, Chiu SY, Ritchie JM, Zecevic D, Cohen LB. Optical recording of action potential propagation in demyelinated frog nerve. Biophys J. 1987 Feb; 51(2):351-5.
    View in: PubMed
  46. Chiu SY, Shrager P, Ritchie JM. Loose patch clamp recording of ionic currents in demyelinated frog nerve fibers. Brain Res. 1985 Dec 16; 359(1-2):338-42.
    View in: PubMed
  47. Shrager P, Chiu SY, Ritchie JM. Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells. Proc Natl Acad Sci U S A. 1985 Feb; 82(3):948-52.
    View in: PubMed
  48. Chiu SY, Schrager P, Ritchie JM. Neuronal-type Na+ and K+ channels in rabbit cultured Schwann cells. Nature. 1984 Sep 13-19; 311(5982):156-7.
    View in: PubMed
  49. Shrager P, Starkus JC, Lo MV, Peracchia C. The periaxonal space of crayfish giant axons. J Gen Physiol. 1983 Aug; 82(2):221-44.
    View in: PubMed
  50. Shrager P, Lo MV. Influence of ionic current on Na+ channel gating in crayfish giant axon. Nature. 1982 Apr 1; 296(5856):450-2.
    View in: PubMed
  51. Lo MV, Shrager P. Block and inactivation of sodium channels in nerve by amino acid derivatives. II. Dependence on temperature and drug concentration. Biophys J. 1981 Jul; 35(1):45-57.
    View in: PubMed
  52. Lo MV, Shrager P. Block and inactivation of sodium channels in nerve by amino acid derivatives. I. Dependence on voltage and sodium concentration. Biophys J. 1981 Jul; 35(1):31-43.
    View in: PubMed
  53. Bean BP, Shrager P, Goldstein DA. Modification of sodium and potassium channel gating kinetics by ether and halothane. J Gen Physiol. 1981 Mar; 77(3):233-53.
    View in: PubMed
  54. Starkus JG, Shrager P. Modification of slow sodium inactivation in nerve after internal perfusion with trypsin. Am J Physiol. 1978 Nov; 235(5):C238-44.
    View in: PubMed
  55. Shrager P. Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents. J Gen Physiol. 1977 Feb; 69(2):183-202.
    View in: PubMed
  56. Jaimovich E, Venosa RA, Shrager P, Horowicz P. Density and distribution of tetrodotoxin receptors in normal and detubulated frog sartorius muscle. J Gen Physiol. 1976 Apr; 67(4):399-416.
    View in: PubMed
  57. Shrager P. Specific chemical groups involved in the control of ionic conductance in nerve. Ann N Y Acad Sci. 1975 Dec 30; 264:293-303.
    View in: PubMed
  58. Shrager P. Ionic conductance changes in voltage clamped crayfish axons at low pH. J Gen Physiol. 1974 Dec; 64(6):666-90.
    View in: PubMed
  59. Shrager P, Profera C. Inhibition of the receptor for tetrodotoxin in nerve membranes by reagents modifying carboxyl groups. Biochim Biophys Acta. 1973 Aug 9; 318(1):141-6.
    View in: PubMed
  60. Shrager P, Tosteson DC, Lauf PK. Biochemical characterization of a lipid-dependent membrane protein antigen in HK sheep red cells. Biochim Biophys Acta. 1972 Dec 1; 290(1):186-99.
    View in: PubMed
  61. Shrager PG, Macey RI, Strickholm A. Internal perfusion of crayfish, giant axons: action of tannic acid, DDT, and TEA. J Cell Physiol. 1969 Aug; 74(1):77-90.
    View in: PubMed
  62. Shrager PG, Strickholm A, Macey RI. Chemical modification of crayfish axons by protein crosslinking aldehydes. J Cell Physiol. 1969 Aug; 74(1):91-100.
    View in: PubMed
  63. Strickholm A, Wallin BG, Shrager P. The pH dependency of relative ion permeabilities in the crayfish giant axon. Biophys J. 1969 Jul; 9(7):873-83.
    View in: PubMed

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