Virginia Tech Student Awarded NIH Grant for Research Into Rett Protein

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by Steve Bryson, PhD |

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A first-generation university student has been awarded a six-year, $466,669 grant from the National Institutes of Health (NIH) to fund his doctoral and postdoctoral research into brain-derived neurotrophic factor (BDNF), a protein that plays a role in Rett syndrome.

The Virginia Tech student, Raymundo Hernandez, called the NIH grant a “dream come true” — one that will help advance his research into the improper neuronal development that occurs in Rett.

“Coming from a non-college background, I am honored to secure this funding to advance my career as a postdoc, and eventually a primary investigator,” Hernandez, a graduate student in the translational biology, medicine, and health (TBMH) program, said in a university press release.

Along with his mentor Michelle Olsen, PhD, a professor at Virginia Tech, Hernandez is investigating how BDNF regulates essential aspects of nerve cell development and maturation.

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Rett is primarily caused by mutations in the MECP2 gene, which carries instructions for the MeCP2 protein that regulates the activity of other genes. A lack of MeCP2 affects brain function and leads to cognitive, sensory, emotional, and motor impairment, as well as problems with breathing, the heart, and digestion.

Studies indicate that BDNF levels are abnormally low in animal models of Rett, and its production coincides with MeCP2 activity, indicating that MeCP2 controls BDNF production. Overproduction of BDNF eased disease symptoms, suggesting it is part of an underlying mechanism of Rett syndrome.

Hernandez originally was thinking he’d pursue a career in psychology, until he took a course in neurobiology and became excited about its concepts.

“Thought, choice, autonomy – I remember being struck by the fact that these concepts we discuss a lot in psychology are fundamentally just brain cells communicating with each other,” said Hernandez. “Suddenly all I wanted to learn about was how brain cells give rise to thoughts and behavior, and how understanding their biology can improve human health.”

Together, Hernandez and Olsen recently published a study demonstrating how the loss of a BDNF receptor molecule on brain cells called astrocytes ━ a type of brain cell that supports the proper function of neurons ━ caused them to shrink by 30%. Over the next two years, Hernandez plans to uncover the effects that occur when BDNF is missing or unable to bind to astrocyte receptors.

“Many neuropsychiatric disorders are related to a lack of this protein,” Olsen said. “By generating a signaling map to fully appreciate the downstream consequences, we move closer to identifying strategies to therapeutically intervene.”

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In the lab, the team is investigating Rett mouse models, which are ideal for understanding how the levels of BDNF affect brain function, Hernandez noted.

“Humans and mice with Rett syndrome lack this growth factor, which we believe could be causing the improper neuronal development and lack of morphological complexity both neurons and astrocytes need to maintain proper signaling,” he said.

Before his doctoral studies at Virginia Tech, Hernandez completed his undergraduate degree at Arizona State University. He now expects to defend his doctoral dissertation in 2023 and hopes to find a postdoctoral fellowship position in a lab that specializes in neuron research.

“Receiving this award is a major accomplishment for Ray and will set him up for success in the years to come,” said Michael Fox, PhD, director of Virginia Tech’s school of neuroscience. “Not only does it show what tremendous potential Ray has for a career in science, it also speaks to the wonderful mentorship he has received from Dr. Olsen, the strength of the TBMH graduate program, and the strength of the growing neuroscience community here at Virginia Tech.”

The NIH grant will fund Hernandez’s ongoing research “into how the brain’s intricate lattice of cells matures,” the university said.