Larry I. Benowitz, Ph.D.
Professor of Surgery and Ophthalmology
Neurosurgery Research/F.M. Kirby Neurobiology Center
Center for Life Sciences 13-071
300 Longwood Avenue
Boston, MA 02115
Spinal cord damage, stroke, and other types of CNS injury can lead to permanent losses in movement, sensation, thinking, and/or other functions. Failure to recover from CNS injury is due in large part to the inability of nerve cells (neurons) to grow new connections to replace ones that have been lost. Our lab has discovered some of the key molecules that control axon growth and has developed methods to promote the rewiring of brain connections after injury.
Using the optic nerve as a classic model of a CNS pathway that normally fails to regenerate after injury, we discovered that if we induce an inflammatory reaction in the eye, macrophages enter and secrete a previously unknown growth factor called oncomodulin. Oncomodulin binds to a high-affinity receptor on neurons and, together with co-factors, causes retinal ganglion cells to revert to an active growth state and begin regenerating axons into the optic nerve. However, even when the intrinsic growth state of nerve cells has been activated, several molecules produced by the non-neuronal cells suppress axon regeneration. Although counteracting these inhibitory molecules is not sufficient to promote extensive regeneration, we find that if we activate the intrinsic growth state of neurons while simultaneously counteracting these inhibitory molecules, we can obtain very dramatic CNS regeneration.
Other research from this lab has shown that the protein kinase Mst3b gets activated in response growth factors and regulates a signal transduction pathway that controls axon growth. Blocking Mst3b expression or activity blocks axon regeneration in vivo. Mst3b can be directly activated using the purine nucleoside inosine, and administration of inosine in an animal model of stroke promotes the rewiring of brain connections and functional recovery.
Our long-term goal is to develop methods to improve outcome after CNS damage.
For a complete listing of publications click here.
Last Update: 12/11/2012