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Larry2Larry Benowitz (larry.benowitz@childrens.harvard.edu)

Dr. Benowitz is the Director of the Laboratories for Neuroscience Research in Neurosurgery and an Associate Professor of Neuroscience at Harvard Medical School. He has contributed over 100 original research articles and review chapters, and is internationally known for his research on molecular mechanisms underlying axonal rewiring after injury in the mature CNS. Dr. Benowitz received his doctorate in the lab of Roger Sperry at Caltech, then did postdoctoral research in the labs of Harvey Karten and Walle Nauta at MIT. He received further postdoctoral training in molecular approaches to the nervous system at McLean Hospital, an affiliate of Harvard Medical School. His research has led to the discovery of several novel approaches to enhance brain reorganization after injury, some of which will soon be going into clinical trials. Dr. Benowitz has trained many predoctoral students and postdoctoral fellows.

At Harvard Medical School, Dr. Benowitz serves as co-chair of the Standing Committee on Awards and Honors, organizes the Advanced Topics in Neurobiology course, and serves on the Steering Committee for the Program in Neuroscience. At Children's Hospital, he is a member of the Research Faculty Council and chair of the Animal Resources committee. Extramurally, he has served on the Central Visual Processing Study Section of the NIH and is on the review board of a major private foundation. Along with continued funding from the NIH (National Eye Insti-tute and the National Institute for Neurological Diseases and Stroke) and from Boston Life Sci-ences, Inc. his laboratory receives funding from the Adelson Program for Neural Repair and Rehabilitation. His research has been written up nationally and internationally, and he was re-cently named by Scientific American as one of the 50 leaders in technology/business/policy for the year 2006. Dr. Benowitz has recently been invited to speak at a number of national and inter-national symposia, including the Gordon Research Conference on Tissue Repair and Regeneration (New Hampshire), National Neurotrauma Society (Washington, DC), 11th International Symposium on Neural Regeneration (Asilomar, CA), International Stroke Conference (Kissimee, FL), Johns Hopkins University School of Medicine, University of North Carolina, Vanderbilt University, Esteve Foundation Symposium (S'Agaro, Spain) and the University of California at Los Angeles.

Professional Positions
1974-1975 Postdoctoral Fellow, Department of Psychology and Brain Sciences, MIT, Cambridge, MA
1975-1977 Postdoctoral Fellow, Dept. Biological Chemistry, Harvard Medical School and McLean Hospital, Belmont, MA
1977-1979 Research Associate in Biological Chemistry, Harvard Medical School and McLean Hospital
1979-1987 Assistant Professor (Psychobiology), Department of Psychiatry, Harvard Medical School, Boston, MA
1979-1990 Associate Biochemist, McLean Hospital
1984- Associate, Program in Neuroscience, Harvard Medical School, Boston, MA
1984-1990 Chief, Laboratory of Developmental Neurobiology and Neuropsychology, McLean Hospital
1987-1990 Associate Professor of Psychiatry (Neuroscience), Harvard Medical School
1990- Associate Professor of Neurosurgery (Neuroscience), Harvard Medical School
1990- Director, Laboratories for Neuroscience Research in Neurosurgery, Children's Hospital

Awards and Other Professional Activities
1974-1975 NIH Postdoctoral Fellowship;1975-1977 Medical Foundation Fellow; 1978-1980 Alfred P. Sloan Foundation Fellow (Neuroscience); 1979-1990 Chairman, Seminar Committee, McLean Hospital; 1980 Harvey Shein Award, McLean Hospital (First prize for submitted paper); 1980 Visiting Scientist, The Open University, Milton Keynes, U.K.; 1984-1987 Consultant for Positron Emission Tomography program, MGH ; 1985-1988 Chairman, Boston Area Neuroscience Group (B.A.N.G.); 1986 Co-Chairman, NRP Conference, Neuroscience Institute, Rockefeller University ; 1987-1989 Neurological Sciences, Visual Sciences B Study Sections, NIH (ad hoc); 1988 Advisory Panel, National Eye Institute, NIH; 1989- Steering Committee, Program in Neuroscience, Harvard Med. School; 1989-1997 Admissions Committee, Program in Neuroscience, Harvard Med. School; 1991- Faculty Council, Children's Hospital; 1994-1997 Awards Committee and Human Resources Comm. (Chair), Children's Hospital; 1993-2001 Editorial Board, Brain Research; 1995- Review committee, Whitehall Foundation; 1997- Visual Sciences B Study Section, National Institutes of Health (Regular member, 2001-); 1997- Co-chair, Standing Committee on Honors and Awards, Harvard Medical School; 1998 Chairman, Symposium on Signaling Pathways and Growth-Associated Proteins in Axon Outgrowth, 12th Biennial Mtg., International Soc. Developmental Neuroscience, Vancouver, B.C.; 1998 Chairman, Symposium on Synaptic Signaling, European Society for Neurochemistry, Saint Petersburg, Russia.; 2001 Plenary speaker, International Symposium on Regeneration, Asilomar, CA; 2002, Keynote speaker, "Neuroscience Day", Medical College of Ohio; 2003, Visiting Professor, Univ. Pennsylvania; 2006 Recipient of Scientific American's Top 50 award.

Selected publications (from a total of 98):

  • Benowitz LI, Yoon MG, Lewis E (1983) Transported proteins in the regenerating optic nerve: regulation by interactions with the optic tectum. Science 222:185-188
  • Benowitz LI, Lewis, E (1983) Increased transport of 44-49,000 dalton acidic proteins during regeneration of the goldfish optic nerve: A 2-dimensional gel analysis. J Neurosci 3:2153-2163.
  • Perrone-Bizzozero NI, Finklestein SP, Benowitz LI (1986) Synthesis of a growth-associated protein by embryonic rat cerebrocortical neurons in vitro. J Neurosci 6:3721-3730.
  • Neve RL, Perrone-Bizzozero NI, Finklestein SP, Zwiers H, Bird E, Kurnit DM, Benowitz LI (1987) The neuronal growth-associated protein GAP-43 (B-50, F1): use of cDNAs to study neuronal specificity, developmental regulation and regional distribution of human and rat mRNAs. Molec Brain Res 2:177-183.
  • Benowitz LI, Apostolides PJ, Perrone-Bizzozero NI, Finklestein SP, Zwiers H (1988) Anatomical localization of the growth-associated protein GAP-43 (B-50) in the adult rat brain. J Neurosci 8:339-352.
  • Moya KL, Benowitz LI, Jhaveri S, Schneider GE (1988) Changes in rapidly-transported proteins in developing hamster retinofugal axons. J Neurosci 8:4445-4454.
  • Neve RL, Finch EA, Bird ED, Benowitz LI (1988) The growth-associated protein GAP-43 is expressed selectively in associative regions of the adult human brain. Proc Natl Acad Sci USA 85:3638-3642.
  • Kosik KS, Orecchio L, Bruns G, Benowitz LI, MacDonald GP, Cox DR, Neve RL (1988) Human GAP-43: Deduced amino acid sequence and chromosonal localization in mouse and human. Neuron 1:127-132.
  • Benowitz LI, Perrone-Bizzozero NI, Finklestein SP, Bird ED (1989) Localization of the growth-associated phosphoprotein GAP-43 in the human cerebral cortex. J Neurosci 9:990-995.
  • Yankner BA, Benowitz LI, Villa-Komaroff L, Neve RL (1990) Transfection of PC12 cells with the human GAP-43 gene: effects on neurite outgrowth and regeneration. Molec Brain Res 7:39-44.
  • Shea TB, Perrone-Bizzozero NI, Beermann ML, Benowitz LI (1991) Phospholipid-mediated delivery of anti-GAP-43 antibodies into neuroblastoma cells prevents neuritogenesis. J. Neurosci. 11:1685-1690.
  • Perrone-Bizzozero NI, Neve RL, Irwin N, Lewis, S, Fischer I, Benowitz, LI (1991) Post-transcriptional regulation of GAP-43 mRNA levels during neuronal differentiation. Molec. Cell. Neurosci. 2:402-409.
  • Schaechter JD and Benowitz LI (1993) Arachidonic acid targets the phosphorylation of GAP-43 in nerve terminals. J. Neurosci. 13:4361-4371.
  • Chong MS, Reynolds ML, Irwin N, Coggeshall RE, Emson P, Benowitz LI and Woolf CJ (1994) GAP-43 expression in primary sensory neurons following central axotomy. J. Neurosci., 14:4375-4384.
  • Schwalb JM, Boulis NM, Gu M-f, Winickoff J, Jackson PS, Irwin N and Benowitz LI (1995) Two factors secreted by the goldfish optic nerve induce retinal ganglion cells to regenerate axons in culture. J. Neurosci., 15:5414-5525.
  • Chao S, Benowitz LI, Krainc D and Irwin N. (1996) Use of a two-hybrid system to identify molecular interactions of GAP-43. Molec. Brain Res., 40:195-202.
  • Benowitz LI and Routtenberg A (1997) GAP-43: an intrinsic determinant of neural development and synaptic plasticity. Trends Neurosci., 20:84-91.
  • Irwin N, Baekelandt VL, Goritchenko L and Benowitz LI (1997) Identification of two proteins that bind to a pyrimidine-rich sequence in the 3' untranslated region of GAP-43 mRNA. Nucl. Acids Res., 25:1281-1288.
  • Benowitz LI, Jing Y, Tabibiazar R, Rosenberg PA, Jo S, Petrausch B, Stuermer C and Irwin N (1998) Axonal regeneration is regulated by an intracellular purine-sensitive mechanism in retinal ganglion cells J. Biol. Chem., 273:29626-29634.
  • Madsen JR, MacDonald P, Irwin N, Goldberg DE, Rimm IJ, Stieg PE and Benowitz LI (1998) Tacrolimus (FK-506) improves functional recovery after spinal cord injury in rats. Exper. Neurol. 154:673-683.
  • Jo S, Wang E and Benowitz, LI (1999) CNTF is an endogenous axon regeneration factor for mammalian retinal ganglion cells. Neuroscience 89:579-591.
  • Benowitz LI, Goldberg DE, Madsen JR, Soni D and Irwin N (1999) Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. Proc. Natl. Acad. Sci, U.S.A. 96:13486-13490.
  • Leon S, Yin Y, Nguyen J, Irwin N and Benowitz LI. (2000) Lens injury stimulates axon regeneration in the mature rat optic nerve. J. Neurosci 20:4615-4626.
  • Kim HA, Pomeroy SL, Whoriskey W, Pawlitzky I, Benowitz LI, Sicinski P, Stiles CD and Roberts TM (2000) A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron 26:405-416.
  • Petrausch B, Tabibiazar R, Roser T, Jing Y, Goldman D, Stuermer CAO, Irwin N, and Benowitz LI. (2000) A purine-sensitive pathway regulates multiple genes involved in axon regeneration in goldfish retinal ganglion cells. J. Neurosci. 20:8031-8041.
  • Benowitz L, Leon S, Tabibiazar R, Jing Y, Irwin N (2001) Axon regeneration in the primary visual pathway of goldfish and rat. In: N. Ingoglia, M. Murray, eds., Nerve Regeneration. M. Dekker and Co. pp. 45-66.
  • Benowitz LI, Goldberg D and Irwin N (2001) A purine-sensitive mechanism regulates the molecular program for axon growth. In: H. W. Müller and M. Bähr, eds., Molecular and Cellular Mechanisms on Brain Repair. Restorative Neurology and Neuroscience (Special Issue), 19: 41-49.
  • Chen, P, Goldberg, DE, Kolb, B, Lanser, M, Benowitz, LI (2002) Inosine induces axonal rewiring and enhances behavioral outcome after stroke. Proc. Natl. Acad. Sci., U.S.A., 99: 1931-1936.
  • Benowitz LI, Goldberg DE, Irwin N (2002) Inosine stimulates axon growth in vitro and in the adult CNS. In: L. McKerracher, G. Doucet, S. Rossignol, eds. Spinal Cord Trauma: Regeneration, Neural Repair and Functional Recovery. Progress in Brain Research 137: 389-400.
  • Irwin N, Chao S, Goritchenko L, Horiuchi A, Greengard P, Nairn A and Benowitz L (2002) Nerve growth factor controls GAP-43 mRNA stability via the phosphoprotein ARPP-19. Proc. Natl. Acad. Sci, U.S.A. 99: 12427-31.
  • Yin Y, Cui Q, Li Y, Irwin N, Fischer D, Harvey AR and Benowitz LI. (2003) Macrophage-derived factors stimulate optic nerve regeneration. J. Neurosci. 23: 2284-2293.
  • Li Y, Irwin N, Yin Y, Lanser M and Benowitz LI. (2003) Axon regeneration in goldfish and rat retinal ganglion cells: differential responsiveness to carbohydrates and cyclic AMP. J. Neurosci. 23: 7830-7838.
  • Fischer D, He Z and Benowitz LI. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J. Neurosci. 24: 8726-8740.
  • 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 (includes journal cover and “News and Views” report by M. Filbin, pp. 715-717).
  • 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.
  • Nakazawa T, Hisatomi T, Nakazawa C, Noda K, Kazuichi M, She H, Matsubara A, Miyahara S, Nakao S, Yin Y, Benowitz L, Hafezi-Moghadam A, Miller JW. Monocyte Chemoattractant Protein-1 mediates retinal detachment-induced photoreceptor apoptosis. Proc. Natl. Acad. Sci., USA, 103: (in press).
  • Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, Hafezi-Moghadam A, Miller JW, Benowitz LI (2006) TNFα mediates oligodendrocyte death and delayed loss of retinal ganglion cells in a mouse model of glaucoma. J. Neuro-sci. 26: 12633-12641.
  • Irwin N, Li Y-M, O’Toole JE and Benowitz LI. (2006) Mst3b, a purine-sensitive Ste20-like kinase, regulates axon outgrowth. Proc. Natl. Acad. Sci., USA, 103: 18320-18325.
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