CLEMSON, South Carolina — Clemson University scientist David Feliciano recently received a three-year, $442,000 grant from the National Institutes of Health to study how alterations to a complex pathway in the developing brain cause a constellation of neurological disorders, including the simultaneous presence of autism and epilepsy.
The project will test the hypothesis that a transporter of amino acids in the brain regulates the "mammalian target of rapamycin" (mTOR) pathway in newborn neurons during fetal and early postnatal development of the cerebral cortex, the outer layer of the brain responsible for integrating sensory information with thought processing.
"The research funded by this grant will be devoted to forming a greater understanding of the upstream signals that turn the mTOR pathway on and off during development," said Feliciano, an assistant professor in the College of Science. "We already know that too much or too little mTOR pathway activity can cause neurological diseases. But no one has yet to show whether amino acids play a critical role in brain development during the perinatal period."
A vast array of changes must successfully occur to create a healthy, fully functioning brain. But deviations in mTOR pathway activity can inhibit these developments, and to further complicate matters, clinicians currently don't possess reliable methods of measuring this activity.
Alterations in the mTOR pathway — whether due to mutations in genes or environmental factors — are linked to neurodevelopmental malformations that might contribute to autism, epilepsy and intellectual delay.
"Our study will focus on the potential role of amino acids during development," said Feliciano, whose research into mTOR began in 2008 when he was a post-doctoral fellow at Yale University in New Haven, Connecticut. There he performed research on Tuberous Sclerosis Complex (TSC). Each neurological disease has its own specific hallmarks. In TSC, clinicians can detect certain red flags by MRI, including abnormalities of the heart, kidney and brain. Additional testing can further illuminate the potential for abnormalities. And in the case of neurological disorders, early detection most often leads to a better prognosis.
"Once a brain is built, there's a little bit of plasticity. But past a certain window, the bricks that have been put in position are cemented in place," Feliciano said. "So you have to think about stopping those bricks from being put in the wrong positions to begin with."
Feliciano hopes to accomplish several aims during the course of the three-year grant. But most importantly, he will strive to determine the role that the amino acid transporter has in neuron development.
"One of the amazing things I've seen during my own career is that wonderful scientists, in a very small window of time, have been able to identify genes that cause certain diseases and have also identified the pathways that are affected by those genes," Feliciano concluded. "And not too long after, they came up with ways to treat patients. My research is yet another step in that direction."
Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke under Award Number 1R15NS096562. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.