PiN Faculty Member - Larry Benowitz, PhD

Larry Benowitz, PhD

Professor of Surgery and Ophthalmology

Boston Children's Hospital
F.M. Kirby Neurobiology Center
Center for Life Science, Room 13-071
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2278
Fax: 617-730-0243

CNS injury, including spinal cord damage, stroke, and certain neurodegenerative diseases, can lead to permanent and devastating functional losses. Our primary objectives are to understand the mechanisms that underlie cell death and regenerative failure after CNS injury, and to develop methods to preserve damaged neurons and promote the rewiring of neural circuitry. One major interest has been regeneration of the optic nerve. Retinal ganglion cells (RGCs), the projection neurons of the eye, normally cannot regrow injured axons and soon begin to die after traumatic nerve injury or in degenerative diseases such as glaucoma. We discovered that regenerative failure can be partially reversed by inducing a controlled inflammatory reaction in the eye, causing neutrophils and macrophages to secrete a previously unknown growth factor, oncomodulin (Ocm). Ocm combined with cAMP elevation and pten gene deletion enables some RGCs to regenerate axons from the eye to the appropriate central target areas, where they form synapses and restore some simple visual responses. More recently, working with Paul Rosenberg and Eric Li, we found that optic nerve injury leads to a rapid elevation of mobile zinc (Zn2+) in the terminals of retinal interneurons (amacrine cells) which then accumulates in RGCs. Chelation of Zn2+ results in the persistent survival of many RGCs and considerable axon regeneration. Current research is investigating the intercellular signaling network underlying this phenomenon, myelination of regenerating axons, synaptic changes in the retina, transcriptional cascades that underlie regeneration, and the use of gene therapy to restore vision in a clinically relevant manner. Other recent interests include the role of microglia in RGC death in animal models of glaucoma, and the role of inosine, a naturally occurring purine nucleoside, in activating the protein kinase Mst3b and promoting anatomical rewiring and functional recovery in animal models of stroke and spinal cord injury.

Last Update: 9/16/2020


For a complete listing of publications click here.



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