Hedong Li, associate research professor of biology, has been awarded $1.8M from the ³Ô¹ÏÍøÕ¾ Institutes of Health (NIH) to study how microRNAs – small segments of genetic material – could be used in treatments for spinal cord injury. The five-year grant builds upon previous work by Li and colleagues to convert glial cells, support cells that surround neurons, into functioning neurons.
“Spinal cord injury, like other neurological injuries and disorders, results in damage to neurons, which cannot regenerate themselves,” said Li. “However, the glial cells that surround neurons can divide and regenerate. Recent work has focused on how to reprogram glial cells into functional neurons for brain repair. We plan to build on this work and to extend the reprogramming process to spinal cord injury.”
Hedong Li, associate research professor of biology (left), and research technologist Mei Jiang.
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.”
