Investigators
Principal Investigator: Aaron DiAntonio (WashU Developmental Biology)
Co-Investigators: Jeffrey Milbrandt (WashU Genetics), Timothy Miller (WashU Neurology)
Description
Our objective is to find new treatments for neuronal injury and disease by promoting regeneration of axons through the “preconditioning” response. Preconditioning is the phenomenon where a prior neuronal injury stimulates an improved regenerative response to a subsequent injury. Our long-term goal is to identify candidate drugs and/or genes that can activate the pro-regenerative preconditioned state without the need for a prior injury. To accomplish this goal, we will study the preconditioning response of human neurons derived from induced pluripotent stem cells (iPSCs). These stem cells are themselves derived from human skin and so are readily accessible and can be derived from patients with neurological disease. These patient-derived iPSCs will allow us to explore cellular models of neurological disease, such as ALS, in which enhanced regeneration would be helpful. If successful, these studies will allow us to perform large-scale screens for factors that promote regeneration of human neurons.
Publications
Frey, E., Valakh, V., Karney-Grobe, S., Shi, Y., Milbrandt, J., and DiAntonio, A. An In Vitro Assay to Study Induction of the Regenerative State in Sensory Neurons. Experimental Neurology Volume 263, Pages 350-363, (2015).
Hao, Y., Frey, E., Yoon, C., Wong, H., Nesterovski, D., Holzman, L., Giger, R.J., DiAntonio, A., and Collins, C. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the DLK kinase. eLife 5:e14048. PMC4896747 (2016).
Frey E, Karney-Grobe S, Krolak T, Milbrandt J, DiAntonio A. TRPV1 Agonist, Capsaicin, Induces Axon Outgrowth after Injury via Ca2+/PKA Signaling. eNeuro. 2018 May 30;5(3). pii: ENEURO.0095-18.2018.
Updated January 2019
Support
This pilot project is made possible by the Danforth Foundation Challenge.
