Neurosciences

School of Medicine

User Tools

Site Tools


faculty:silver:index

Jerry Silver, Ph.D.

Jerry Silver, Ph.D.
Professor
Department of Neurosciences
Case Western Reserve University


School of Medicine E653
10900 Euclid Ave
Cleveland OH, 44106-4975

Phone : (216) 368-2150
Fax : (216) 368-4650
Email : jxs10@case.edu
 
 

ABOUT DR. JERRY SILVER

Dr. Silver received his Ph.D. from Case Western Reserve in 1974 and was the recipient of the Herbert S. Steuer Memorial Award for Meritorious Original Research in Anatomy. He did post-doctoral work at Harvard University in the Department of Neurosciences at The Children’s Hospital and in the Neuropathology Department at Harvard Medical School. Dr. Silver is currently Professor in the Department of Neurosciences at the Case Western Reserve University School of Medicine and adjunct Professor in the Department of Neurosurgery at the Cleveland Clinic Foundation. Dr. Silver is a recipient of several prestigious awards. In 2003 he was awarded the Ameritec Prize for significant accomplishments toward a cure for paralysis. This prize was established in 1987 specifically to recognize scientists whose research advances the search towards a cure for paralysis. In 2003 he was also honored with the Christopher Reeve-Joan Irvine Research Medal (The Reeve-Irvine Medal) for critical contributions that may lead to the promotion of repair of the damaged spinal cord. The prize acknowledges the most meritorious science, a proven body of work that has withstood the test of time and scrutiny, as well as other enriching contributions to the field. In 2004 Dr. Silver received a Jacob Javits Neuroscience Investigator Award for his long-standing grant entitled “Factors affecting regeneration through the glial scar.” This is a highly prestigious award that recognizes a select group of NIH grantees who have made seminal contributions to their field of neuroscience, have contributed exemplary service to the NIH, and who show great promise for continuing their cutting edge research well into the future. Dr. Silver was named the recipient of the 2008 Erica Nader Award, which is given through the American Spinal Injury Association (ASIA). The award honors “breakthrough research in the field of spinal cord injury”. In 2011 he was honored to become a fellow of the American Association for the Advancement of Science (AAAS). Dr. Silver has served on a number of editorial boards including the journals Glia, The Journal of Neurocytology, Developmental Neurobiology, The Journal of Neuroscience and Experimental Neurology (where he is a Section Editor). He regularly reviews articles for over 35 high impact journals and he reviews grants for 18 national and international organizations. He has served on a variety of NIH study sections since 1982 including the Neurobiology Review Group, Neurology B2, The Visual Sciences C Study Section, and the Clinical Neurology, Neurotransmitters and Transplantation Study Section. He has been appointed as a regular member of the Scientific Advisory Council of the Christopher Reeve Foundation and of the Scientific Board of the International Spinal Research Trust (England). He has served as lead or senior author on more than 160 publications.

RESEARCH INTERESTS

The ultimate goal of the Silver lab is to understand the basic biology that underlies axonal dieback and regeneration failure in the adult spinal cord and then use this knowledge to develop strategies to maximally overcome the lack of regeneration after both incomplete and complete cord injury in order to promote functional repair. Although highly controversial from its inception, the Silver lab was one of the very first to suggest that overtly growth repulsive environments, whose function was to actively turn axons away from improper trajectories during embryogenesis, might reappear in the injured CNS and block the attempt of severed axons to re-grow. One of the most interesting families of inhibitory extracellular matrix molecules, the lectican family of sulfated proteoglycans and, in particular, the chondroitin sulfate proteoglycans (CSPGs), were first discovered by the Silver lab in the early 1990’s to be involved in creating such developmental as well as regenerative glial boundaries. But why did axons in the embryo turn away from CSPGs but in the adult after injury become entrapped within substrates occupied by proteoglycans? Nearly 2 decades after CSPGs had first been implicated in regeneration failure, the Silver lab was a major collaborator in the discovery of the first neuronal receptors for CSPGs that bind specifically to the sugar chains of proteoglycans and mediate the newly appreciated entrapment phenomenon. Indeed, two members of the pro-synaptic, LAR family of receptor protein tyrosine phosphatases which up-regulate in growth cones when they encounter proteoglycan gradients are the major receptors on neurons that are involved with the overly adhesive properties of this family of ECM inhibitors. The lab has now generated small peptides, administered simply by sub-cutaneous injection, that block these receptors on damaged neurons in the moderately contused spinal cord thereby releasing axons from proteoglycan mediated entrapment. Behavioral recovery in partially paralyzed animal models particularly after administration of the peptide that blocks the sigma (RPTPσ) member of this receptor family is especially impressive, presenting a potential new avenue of non-invasive treatment for paralysis. In addition, the lab has now demonstrated that systemic delivery of the peptide has strong efficacy in promoting regeneration and functional recovery in a wide variety of conditions such as following ischemic heart attack and peripheral nerve avulsion injury where proteoglycans within scar tissue block nerve regeneration. There are many individuals who have complete, gaping lesions of the spinal cord with no function below the level of injury. Are there strategies that can help build a regeneration bridge across the gap? An especially exciting development is our recent demonstration that combining the classical use of segments of autologous peripheral nerves as “bridges” to bypass a hemisection lesion of the adult rat spinal cord combined with inhibitory matrix modification via chondroitinase or LAR blocking peptides at the PNS/CNS interfaces, allows regenerating axons to exit the bridge, form functional synapses, and restore useful movement to the once completely paralyzed forelimb as well as remarkably robust functional recovery to the hemidiaphragm. The lab is now showing for the first time that a novel modification of this strategy in a complete thoracic transection injury model and with the further addition of the trophic factor FGF can allow for an unprecedented amount of regeneration of certain brainstem neurons well past the graft site all the way to lumbo-sacral levels with restoration of near normal bladder control. The labs research strategy shows clearly, for the first time, that long distance regeneration, with appropriate re-formation of functional connections, can be achieved in the adult after catastrophic spinal cord injury providing real hope that we are now entering an era where strategies for providing functional benefit in animal models of spinal cord injury are sufficiently robust that there should be optimism for translational success. Many other labs around the world are now showing with the use of a variety of proteoglycan or proteoglycan receptor modifying techniques, coupled with various other strategies for enhancing the intrinsic growth response of neurons, that such combinatorial strategies can foster a good measure of functional plasticity as well as frank regeneration in a wide variety of CNS injury models.

LAB MEMBERS

RESEARCH ASSISTANTS

Bruce You: jxy268@case.edu

GRADUATE STUDENTS

Amanda Tran: apt26@case.edu

Jared Cregg: jmc205@case.edu

Marc DePaul: mxd359@case.edu

MEDICAL SCHOOL STUDENTS

Eli Goshorn: esg37@case.edu

UNDERGRADUATES

Tara Phuongnhi Tran: tpt7@case.edu

PAST LAB MEMBERS

Bradley Lang: Athersys, btl21@case.edu

Sarah Busch: Senior Scientist at Athersys, sab37@case

Angela Nord: Post-doctoral Fellow at Case Western, arn29@case

Teresa Evans: MSTP 4th year medical student

Alicia Hawthorne: PhD, Postdoctoral Fellow, Emory University, alicia.l.hawthorne@emory.edu

Himanshu Sharma: MSTP at NY Stony Brook

Warren Alilain: Professor at Metro Health

Bornali Kundu: Resident in Salt Lake City

Ben Brown: MD/PhD student, Vanderbilt University, bbrown11@mail.bw.edu

Veronica Tom: Assistant Professor in the Department of Neurobiology and Anatomy, veronica.Tom@drexelmed.edu

Fernando Cuascut: MD Neurology Resident SUNY Downstate Medical Center

SELECTED PUBLICATIONS

  1. Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J. (2005)
    The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Mol Cell Neurosci. 2005 Jan; 28(1):18-29.
  2. Tom VJ, Doller CM, Malouf AT, Silver J. (2004)
    Astrocyte-associated fibronectin is critical for axonal regeneration in adult white matter. J Neurosci. 2004 Oct 20; 24(42):9282-9290.
  3. Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J. (2004)
    Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J Neurosci. 2004 Jul 21; 24(29):6531-6539.
  4. Grimpe B, Silver J. (2004)
    A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J Neurosci. 2004 Feb 11; 24(6):1393-1397.
  5. Silver J, Miller JH. (2004)
    Regeneration beyond the glial scar. Nat Rev Neurosci. 2004 Feb; 5(2):146-156.
  6. Butler CD, Schnetz SA, Yu EY, Davis JB, Temple K, Silver J, Malouf AT. (2004)
    Keratan sulfate proteoglycan phosphacan regulates mossy fiber outgrowth and regeneration. J Neurosci. 2004 Jan 14; 24(2):462-473.
  7. Hendricks TJ, Fyodorov DV, Wegman LJ, Lelutiu NB, Pehek EA, Yamamoto B, Silver J, Weeber EJ, Sweatt JD, Deneris ES. (2003)
    Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior. Neuron. 2003 Jan 23; 37(2):233-247.
  8. Grimpe B, Silver J. (2002)
    The extracellular matrix in axon regeneration. Prog Brain Res. 2002; 137:333-349.
  9. Grimpe B, Dong S, Doller C, Temple K, Malouf AT, Silver J. (2002)
    The critical role of basement membrane-independent laminin gamma 1 chain during axon regeneration in the CNS. J Neurosci. 2002 Apr 15; 22(8):3144-3160.
  10. Silver J. (2001)
    Robust regeneration in the adult optic system. Exp Neurol. 2001 Dec; 172(2):255-256.
  11. Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. (1999)
    Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci. 1999 Oct 1; 19(19):8182-8198.
  12. Davies SJ, Goucher DR, Doller C, Silver J. (1999)
    Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci. 1999 Jul 15; 19(14):5810-5822.
  13. Xu K, Malouf AT, Messing A, Silver J. (1999)
    Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. Glia. 1999 Feb 15; 25(4):390-403.
  14. DeWitt DA, Perry G, Cohen M, Doller C, Silver J. (1998)
    Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease. Exp Neurol. 1998 Feb; 149(2):329-340.
  15. Fitch MT, Silver J. (1997)
    Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Exp Neurol. 1997 Dec; 148(2):587-603.
  16. Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. (1997)
    Regeneration of adult axons in white matter tracts of the central nervous system. Nature. 1997 Dec 18-25; 390(6661):680-683.
  17. Fitch MT, Silver J. (1997)
    Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. Cell Tissue Res. 1997 Nov; 290(2):379-384.
  18. DeWitt DA, Silver J. (1996)
    Regenerative failure: a potential mechanism for neuritic dystrophy in Alzheimer's disease. Exp Neurol. 1996 Nov; 142(1):103-110.
  19. Canning DR, Hoke A, Malemud CJ, Silver J. (1996)
    A potent inhibitor of neurite outgrowth that predominates in the extracellular matrix of reactive astrocytes. Int J Dev Neurosci. 1996 Jun; 14(3):153-175.
  20. Hoke A, Silver J. (1996)
    Proteoglycans and other repulsive molecules in glial boundaries during development and regeneration of the nervous system. Prog Brain Res. 1996; 108:149-163.
  21. McKeon RJ, Hoke A, Silver J. (1995)
    Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol. 1995 Nov; 136(1):32-43.
  22. Brittis PA, Lemmon V, Rutishauser U, Silver J. (1995)
    Unique changes of ganglion cell growth cone behavior following cell adhesion molecule perturbations: a time-lapse study of the living retina. Mol Cell Neurosci. 1995 Oct; 6(5):433-449.
  23. Brittis PA, Silver J. (1995)
    Multiple factors govern intraretinal axon guidance: a time-lapse study. Mol Cell Neurosci. 1995 Oct; 6(5):413-432.
  24. Brittis PA, Meiri K, Dent E, Silver J. (1995)
    The earliest patterns of neuronal differentiation and migration in the mammalian central nervous system. Exp Neurol. 1995 Jul; 134(1):1-12.
  25. Silver J. (1994)
    Inhibitory molecules in development and regeneration. J Neurol. 1994 Dec; 242(1 Suppl 1):S22-S24.
  26. Hoke A, Canning DR, Malemud CJ, Silver J. (1994)
    Regional differences in reactive gliosis induced by substrate-bound beta-amyloid. Exp Neurol. 1994 Nov; 130(1):56-66.
  27. Gonzalez ML, Silver J. (1994)
    Axon-glia interactions regulate ECM patterning in the postnatal rat olfactory bulb. J Neurosci. 1994 Oct; 14(10):6121-6131.
  28. DeWitt DA, Richey PL, Praprotnik D, Silver J, Perry G. (1994)
    Chondroitin sulfate proteoglycans are a common component of neuronal inclusions and astrocytic reaction in neurodegenerative diseases. Brain Res. 1994 Sep 5; 656(1):205-209.
  29. Frisa PS, Goodman MN, Smith GM, Silver J, Jacobberger JW. (1994)
    Immortalization of immature and mature mouse astrocytes with SV40 T antigen. J Neurosci Res. 1994 Sep 1; 39(1):47-56.
  30. Brittis PA, Silver J. (1994)
    Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. Proc Natl Acad Sci U S A. 1994 Aug 2; 91(16):7539-7542.
  31. Herrup K, Silver J. (1994)
    Cortical development and topographic maps: patterns of cell dispersion in developing cerebral cortex. Curr Opin Neurobiol. 1994 Feb; 4(1):108-111.
  32. Hoke A, Silver J. (1994)
    Heterogeneity among astrocytes in reactive gliosis. Perspect Dev Neurobiol. 1994; 2(3):269-274.
  33. Canning DR, McKeon RJ, DeWitt DA, Perry G, Wujek JR, Frederickson RC, Silver J. (1993)
    beta-Amyloid of Alzheimer's disease induces reactive gliosis that inhibits axonal outgrowth. Exp Neurol. 1993 Dec; 124(2):289-298.
  34. Gonzalez Mde L, Malemud CJ, Silver J. (1993)
    Role of astroglial extracellular matrix in the formation of rat olfactory bulb glomeruli. Exp Neurol. 1993 Sep; 123(1):91-105.
  35. Goodman MN, Silver J, Jacobberger JW. (1993)
    Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines. Brain Res. 1993 Aug 13; 619(1-2):199-213.
  36. DeWitt DA, Silver J, Canning DR, Perry G. (1993)
    Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer's disease. Exp Neurol. 1993 Jun; 121(2):149-152.
  37. Pindzola RR, Doller C, Silver J. (1993)
    Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during development and after root and sciatic nerve lesions. Dev Biol. 1993 Mar; 156(1):34-48.
  38. Silver J, Edwards MA, Levitt P. (1993)
    Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain. J Comp Neurol. 1993 Feb 15; 328(3):415-436.
  39. Silver J. (1993)
    Glia-neuron interactions at the midline of the developing mammalian brain and spinal cord. Perspect Dev Neurobiol. 1993; 1(4):227-236.
  40. Brittis PA, Canning DR, Silver J. (1992)
    Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science. 1992 Feb 7; 255(5045):733-736.
  41. McKeon RJ, Schreiber RC, Rudge JS, Silver J. (1991)
    Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci. 1991 Nov; 11(11):3398-3411.
  42. Lefkowitz M, Durand D, Smith G, Silver J. (1991)
    Electrical properties of axons within probst bundles of acallosal mice and callosi that have reformed upon glial-coated polymer implants. Exp Neurol. 1991 Sep; 113(3):306-313.
  43. Watanabe M, Rutishauser U, Silver J. (1991)
    Formation of the retinal ganglion cell and optic fiber layers. J Neurobiol. 1991 Jan; 22(1):85-96.
  44. Rudge JS, Silver J. (1990)
    Inhibition of neurite outgrowth on astroglial scars in vitro. J Neurosci. 1990 Nov; 10(11):3594-3603.
  45. Schneider BF, Silver J. (1990)
    Failure of the subcallosal sling to develop after embryonic X-irradiation is correlated with absence of the cavum septi. J Comp Neurol. 1990 Sep 22; 299(4):462-469.
  46. Snow DM, Lemmon V, Carrino DA, Caplan AI, Silver J. (1990)
    Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol. 1990 Jul; 109(1):111-130.
  47. Siegal JD, Kliot M, Smith GM, Silver J. (1990)
    A comparison of the regeneration potential of dorsal root fibers into gray or white matter of the adult rat spinal cord. Exp Neurol. 1990 Jul; 109(1):90-97.
  48. Kliot M, Smith GM, Siegal JD, Silver J. (1990)
    Astrocyte-polymer implants promote regeneration of dorsal root fibers into the adult mammalian spinal cord. Exp Neurol. 1990 Jul; 109(1):57-69.
  49. Smith GM, Rutishauser U, Silver J, Miller RH. (1990)
    Maturation of astrocytes in vitro alters the extent and molecular basis of neurite outgrowth. Dev Biol. 1990 Apr; 138(2):377-390.
  50. Snow DM, Steindler DA, Silver J. (1990)
    Molecular and cellular characterization of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier. Dev Biol. 1990 Apr; 138(2):359-376.
  51. Rudge JS, Smith GM, Silver J. (1989)
    An in vitro model of wound healing in the CNS: analysis of cell reaction and interaction at different ages. Exp Neurol. 1989 Jan; 103(1):1-16.
  52. Hankin MH, Silver J. (1988)
    Development of intersecting CNS fiber tracts: the corpus callosum and its perforating fiber pathway. J Comp Neurol. 1988 Jun 8; 272(2):177-190.
  53. Hankin MH, Schneider BF, Silver J. (1988)
    Death of the subcallosal glial sling is correlated with formation of the cavum septi pellucidi. J Comp Neurol. 1988 Jun 8; 272(2):191-202.
  54. Webster MJ, Shatz CJ, Kliot M, Silver J. (1988)
    Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats. J Comp Neurol. 1988 Mar 22; 269(4):592-611.
  55. Holley JA, Silver J. (1987)
    Growth pattern of pioneering chick spinal cord axons. Dev Biol. 1987 Oct; 123(2):375-388.
faculty/silver/index.txt · Last modified: 2015/04/28 13:40 by tpt7