DNA photo
  Children's Hospital Research  Children's Hospital Labs
Larry Benowitz, PhD  Children's logo  Harvard logo
 Larry Benowitz, PhD
 X  X
Image
   Department  Neurosurgery
   Hospital Title  Director, Laboratories for Neuroscience
Research in Neurosurgery
   Academic Title  Professor
   Phone  617 919 2278
   Fax  617 919 2380
   Email  Larry Benowitz
   Location  300 Longwood Avenue
CLS 13071
Boston MA 02115
Research Overview

Under normal circumstances, neurons in the mature central nervous system (CNS: brain, spinal cord, eye) cannot re-establish their connections after injury, nor can intact cells grow new connections to compensate for those that have been lost. As a result of this, victims of traumatic injury, stroke or neurodegenerative diseases can suffer permanent and often devastating losses in movement, sensation, bodily functions, and thinking. The goals of the Benowitz lab are to discover the basic mechanisms that control the growth of nerve connections and to apply insights from this work to promote regeneration and functional recovery after CNS injury.

Current projects focus on:
  • Optic nerve regeneration: research on the molecular signals that enable the projection neurons of the eye (retinal ganglion cells) to regrow their connections through the optic nerve.

  • Stroke and spinal cord injury: methods to enhance the rewiring of brain connections and improve functional outcome after stroke or spinal cord injury.

  • Inosine and cell signaling pathways: the small, naturally occurring molecule, inosine, stimulates certain types of nerve cells to extend nerve fibers in cell culture and in vivo. Inosine appears to stimulate a cell signaling pathway that controls the expression of a group of genes required for axon growth.
About Larry Benowitz

Larry Benowitz received his PhD in Biology from CalTech and completed fellowships at CalTech, MIT, and Harvard Medical School. He joined the faculty of Harvard Medical School in 1979, where he is currently a Professor of Surgery and Director of the Laboratories for Neuroscience Research in Neurosurgery at Children's Hospital.

At Children's Hospital, he serves on the Research Faculty Council, the Surgical Research Council, and chairs the Steering Committee for Animal Resources (ARCH). At Harvard Med School, he is the Co-chair of the Committee on Awards and Honors and has taught in a number of courses. Extramurally, he serves on the review boards of the Journal of Neuroscience and the Journal of Neurosurgery and has served on review committees for the NIH and private foundations. He has been invited to speak at many research centers and symposia, including most recently the University of Southern California/UCLA/UC Irvine workshop on Plasticity and Repair in Neurodegenerative Disorders, Williams College, The Wadsworth Center/SUNY Albany, the University of Massachusetts Medical Center, Northwestern Univ. Med. Ctr., an NIH Roadmap Workshop on Transforming Regenerative Medicine, the American Academy of Neurology Symposium on the "Future of Neuroscience", the Wings for Life Spinal Cord Research Foundation Symposium (Salzburg, Austria), the Symposium on Development and Plasticity of the Nervous System at the University of Rio de Janeiro (Brazil), the Lasker/IRRF Initiative for Innovation in Vision Research, and at the Burke Institute/Cornell Medical Center. His research has been reported in the international media and has received television coverage on CBS, CNN and the BBC.

Key Publications
  • Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT, Jiang F, Langer R, Benowitz LI (2006) Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nature Neuroscience 9: 843-852.
  • Piantino J, Burdick JA, Goldberg D, Langer R, Benowitz LI (2006) An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp. Neurol. 201: 359-367.
  • Irwin N, Li Y-M, O'Toole JE and Benowitz LI (2006) Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth. Proc. Natl. Acad. Sci., U.S.A. 103: 18320-18325.
  • Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, Michaud N, Hafezi-Moghadam A., Miller JW and Benowitz LI (2006) Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J. Neurosci 26: 12633-12641.
  • Benowitz LI, Yin Y (2007) Combinatorial treatments for promoting axon regeneration in the CNS: Strategies for overcoming inhibitory signals and activating neurons' intrinsic growth state. Dev Neurobiol 67: 1148-1165.
  • Benowitz L, Yin Y (2008) Rewiring the injured CNS: Lessons from the optic nerve. Exp Neurol. 209:389-398.
  • Seijffers R and Benowitz LI (2008) Intrinsic Determinants of Axon Regeneration. In: J. Kordower and M. Tuszynski, editors, "CNS Regeneration: Basic Science and Clinical Advances", 2nd ed., Ch. 1, pp. 2-41, Academic Press/Elsevier, New York, Amsterdam.
  • Cui Q, Yin Y and Benowitz LI (2009) The Role of Macrophages in Optic Nerve Regeneration. Neuroscience 158:1039-1048. (Special issue, U. Dirnagl and J. Schwab, editors, "Brain Immune interaction").
  • Zai L, Ferrari C, Subbaiah S, Havton L, Coppola G, Strittmatter S, Irwin N, Geschwind D and Benowitz L (2009) Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb. J. Neurosci. 29: 8187-8197.
  • Lorber B, Howe ML, Benowitz LI and Irwin N (2009) Mst3b, an Ste20-like kinase, regulates axon regeneration in the mature CNS and PNS. Nature Neuroscience, 12:1407-1414
  • Yin Y, Cui Q, Gilbert H, Yang Y, Yang Z, Berlinicke C, Li Z, Zaverucha-do-Valle C, He H, Petkova V, Zack D, Benowitz LI (2009) Oncomodulin links inflammation to optic nerve regeneration. Proc. Natl. Acad. Sci. USA, in press PMID: 19875691
  • Benowitz L and Carmichael, TS. Promoting axonal rewiring to improve outcome after stroke. Neurobiology of Disease, in press.
 X  X