Previous research led by Li’s colleagues at Penn State revealed that injecting a transcription factor called NeuroD1 into an injured mouse brain converts glial cells into functional neurons. However, the mechanism behind this reprogramming process is unclear.
“I believe that microRNAs, which play a pivotal role during neurodevelopment, are also essential to the reprograming process,” said Li. “With this grant, I plan to systematically identify which of the many types of microRNA are most involved in this process. Then I will consider how to use microRNAs to initiate reprogramming.”
While transcription factors require complex systems to be delivered to injured cells, microRNAs can be delivered much more easily. MicroRNAs are small molecules and can be chemically synthesized, so they theoretically could be developed into synthetic drugs and modified to improve potency, efficiency, and specificity.
Li also plans to investigate how to reprogram glial cells into different types of neurons.
“In order to form optimal neuronal circuitry for functional repair, one would assume that we need both excitatory and inhibitory neurons, which perform different roles in the nervous system,” said Li. “We hypothesize that we can use microRNAs to generate diversified neuronal subtypes from this reprogramming process.”
Li hopes to determine which microRNAs, either individually or in combination, lead to the most efficient reprogramming of glial cells into diverse neuronal subtypes.
“I developed an interest in this line of research when I was a postdoctoral researcher at the Spinal Cord Injury Center at Rutgers University, where I met several patients with spinal cord injury,” said Li. “I ultimately hope that my research helps understand the molecular mechanisms of the neuronal reprogramming process and leads to novel therapeutic treatments for spinal cord injury and other neurological disorders.”