Larry Benowitz, PhD

  • Professor of Ophthalmology (part-time)

Larry Benowitz received his PhD from Caltech with Nobel Laureate Roger Sperry and did postdoctoral fellowships at MIT and Harvard before joining the Harvard Medical School faculty, where he is currently a Professor of Neurosurgery and Ophthalmology. In 2016, he was the named the first incumbent of the Neurosurgical Innovation and Research Professorship at Boston Children’s Hospital. Upon closing his lab and going into semi-retirement in Boston, Dr. Benowitz has been appointed as a Professor of Ophthalmology (Part-time) at the University of Pittsburgh.

Representative 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.

Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, Hafezi-Moghadam A, Miller JW, Benowitz LI (2006) TNFa mediates oligodendrocyte death and delayed loss of retinal ganglion cells in a mouse model of glaucoma. J. Neurosci. 26: 12633-12641.

Zai L, Ferrari C, Dice C., Subbaiah S, Havton L, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter S and Benowitz LI (2011) Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke. J. Neurosci. 31: 5977– 5988.

De Lima S, Koriyama Y, Kurimoto T, Oliveira JT, Yin Y, Li Y, Gilbert HY, Fagiolini M, Martinez AMB, and Benowitz LI (2012) Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc. Natl. Acad. Sci. USA 109: 9149-9154.

Li Y, Andereggen L, Yuki K, Omura K, Yin Y, Gilbert HY, Erdogan B, Asdourian MS, Shrock C, de Lima S, Apfel UP, Zhuo Y, Hershfinkel M, Lippard SJ, Rosenberg PA, Benowitz L. (2017) Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration. Proc Natl Acad Sci U S A 114(2):E209-E218.

Xie L, Yin Y, Benowitz LI. Chemokine (2021) CCL5 induces robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy. Proc. Natl. Acad. Sci., U.S.A., 118(9):e2017282118. PMID: 33627402

Xie L, Cen LP, Li YQ, Gilbert HY, Berlinicke C, Stavarache MA, Cui Q, Kaplitt MG, Zack DJ, Benowitz LI*, Yin Y* (2022) Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells’ response to PTEN deletion. Proc. Natl. Acad. Sci., U.S.A 119(15):e2113751119. PMID: 35394873 *senior and corresponding authors

Cheng Y, Yin Y, Zhang A, Bernstein AM, Kawaguchi R, Gao K, Potter K, Gilbert HY, Ao Y, Ou J, Fricano-Kugler CJ, Goldberg JL, Woolf CJ, Sofroniew MV, Benowitz LI*, Geschwind DH* (2022) Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration. Nat Commun. 13:4418. PMID: 30569210. *senior and corr. authors.

Research Interests

Dr. Benowitz has had a long-standing interest in the rewiring of CNS circuits after injury, with a particular focus on regeneration of the optic nerve. Although the mature optic nerve normally cannot regenerate when injured, Dr. Benowitz discovered that intraocular inflammation enables retinal ganglion cells (RGCs) to regenerate lengthy axons beyond the injury site, and identified the small Ca2+-binding protein oncomodulin (Ocm) and the chemokine SDF1 as the primary mediators of this phenomenon. Combining intraocular inflammation with a cAMP analog and pten gene deletion enables some RGCs to regenerate axons from the eye to appropriate target areas in the brain. Following up on this work, his group now identified the receptor through which Ocm promotes regeneration in the optic nerve, peripheral nerves, and spinal cord. Other recent work has identified the chemokine CCL5 as the primary mediator of optic nerve regeneration induced by ciliary neurotrophic factor (CNTF) gene therapy, and identified the transcriptional repressor REST/NRSF as a major regulator of the transcriptional program underlying optic nerve regeneration. In other work, his group discovered that free/mobile zinc (Zn2+) increases in the inner retina shortly after optic nerve injury, and that chelating Zn2+ enables many injured RGCs to survive long-term and regenerate axons. His most recent research further examined the transcription cascade underlying the regenerative program, understanding how Zn2+ levels are regulated in the retina through elevation of nitric oxide in amacrine cells, and how this in turn regulates RGC survival and optic nerve regeneration; and clinically relevant approaches to CNS regeneration. In earlier work, Dr. Benowitz investigated the role of microglial activation and TNF-a in glaucoma; the role of inosine in promoting rewiring of the corticospinal tract and functional recovery after SCI and stroke; Mst3b as a key regulator of axon regeneration; the relationship of GAP-43 to brain development and plasticity; and cognitive functions mediated by the right cerebral hemisphere in man. Dr. Benowitz has published over 120 papers in the primary literature, many reviews, and has trained dozens of students and postdoctoral fellows over the years. In 2006 he was named by Scientific American as one of the 50 leaders of the year in science and technology, in 2013/14 he was awarded the Lewis Rudin Glaucoma Prize for “the most significant scholarly article on glaucoma published in a peer-reviewed journal in the prior year”, and has been invited to deliver several named lectureships. He holds several patents related to promoting brain rewiring after injury.