Publication Date




Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Neuroscience (Medicine)

Date of Defense


First Committee Member

Vance P. Lemmon

Second Committee Member

Stephan Zuchner

Third Committee Member

John L. Bixby

Fourth Committee Member

Nagi Ayad

Fifth Committee Member

Jae K. Lee

Sixth Committee Member

Jeffery A. Plunkett


Following traumatic central nervous system (CNS) injury, most severed axons fail to regenerate beyond the glial scar. This results in persistent deficits, including paralysis. Regenerative failure is due to neuron-intrinsic and extrinsic factors (i.e. CNS glial cells). Astrocytes are interesting extrinsic factors because they are a major constituent of the glial scar. After injury, astrocyte phenotypes change in a process called reactive gliosis. Reactive astrocytes are characterized by expansion of their glial fibrillary acid protein (GFAP) cytoskeleton and increased expression of axon-growth inhibitory chondroitin sulfate proteoglycans (CSPGs). As there are no FDA-approved drugs that enhance regeneration or functional recovery, there is a need to develop effective therapies. One strategy to address this need is to pharmacologically stimulate neuron-intrinsic axon growth programs while not exacerbating undesirable characteristics from reactive astrocytes. We developed and then utilized novel high content analysis assays for counter-screening neurite growth-promoting kinase inhibitors on cultured astrocytes. This led to the identification of two compounds that enhance axon growth on glial substrates. In the future, we aim to parlay knowledge about how compounds affect signaling networks in both neurons and astrocytes in order to develop agents that promote functional recovery after CNS injury.


Astrocyte; Glial Scar; Kinase; Axon Regeneration; Spinal Cord Injury; Traumatic Brain Injury