Researchers dream of helping patients with permanent nerve damage to walk—or run, or swim—again. Before they can rebuild damaged nerves, however, scientists must truly understand how healthy nerves develop in the first place.
That's where Alex Kolodkin comes in. His goal is to learn how proteins act as "guidance cues" for growing nerves, alternately repelling and attracting growth to keep a developing nerve on the right track inside the body. To define the basic principles of complex nervous system organization, his lab works to identify genes in a fruit fly model and studies those newfound molecules in mice for a clearer picture of how they spur mammalian development.
Kolodkin launched his career with work that has already come to be regarded as classic. As a postdoctoral fellow, he led the discovery of the largest known family of repulsive guidance cues—a family of proteins called semaphorins, which can function to prevent neurons from extending or migrating into the wrong areas.
Kolodkin followed that work with a half-dozen more major finds, some surprising. In addition to finding key semaphorin receptors, his lab discovered a potential therapeutic target for regeneration of nerve axons: flavoprotein oxidoreductase, which helps to regulate semaphorin-mediated repulsion. He and his colleagues also demonstrated that the protein Sema7A binds to receptor molecules known as integrins to encourage axon growth rather than inhibit it—surprising many scientists, who had assumed a different receptor and action for Sema7A.
Semaphorins are just one of the protein families that guide nerve growth. Kolodkin hopes to define the fundamental principles that all such families of guidance cues use to build, maintain, and modulate neural connections.