The CASK gene is found across the animal kingdom, but some rare variants of the gene in children can cause seizures, blindness, cognitive impairments, and movement disorders.

Only a few hundred cases of these genetic diseases have been reported in humans worldwide, but researchers at Virginia Tech are studying CASK to understand its role in healthy brain development.

“By studying the gene’s variants, we’re uncovering clues about the molecular pathways underlying neural circuit formation in the developing brain and the maintenance of function into adulthood to help address neurological disease,” said Paras Patel, a Virginia Tech student in the Translational Biology, Medicine, and Health (TBMH) Program.

Patel, who works in the lab of Konark Mukherjee, assistant professor at the Fralin Biomedical Research Institute at VTC, was recently awarded a two-year National Institutes of Health Ruth L. Kirschstein Predoctoral Individual National Research Service Award to support his research on the gene’s function in brain development and maintenance.

Babies with CASK gene variants typically develop normally during pregnancy. Symptoms, such as a small head size and vision problems, don’t arise until weeks or months after birth when two brain regions – the cerebellum and the optic nerve – spontaneously shrink.

“The brain cells develop normally, but then the consequences of CASK mutations manifest at a certain age, activating a series of molecular cues that cause cells in these very specific brain regions to die,” Mukherjee said. “This is compelling because the rest of the body’s cells with this mutated gene are unaffected, so CASK appears to play a differential role in maintaining different parts of a healthy nervous system.”

Over the next two years, Patel will investigate why only certain brain cells are directly affected by the mutated gene. He previously developed experimental models that cause deterioration in only the optic nerve, the cerebellum, or both brain regions by deleting the gene in certain brain cell types in laboratory mice.

Comparing these models will help Patel and Mukherjee uncover clues about the cell types involved, how the mutation impacts their ability to send chemical signals to neighboring cells, and whether cell death is self-programmed or due to external influences.

Learning more about these previously unknown gene functions could aid in developing treatment strategies for CASK-related health problems in humans and provide insight into more common diseases.

The lab previously discovered that deleting CASK in the supportive cells surrounding the optic nerve, but not the neurons that make up the nerve fibers, caused the optic nerve to degrade. The research team also identified key molecular differences between males and females with the genetic mutation.

Patel, who grew up in Roanoke, earned a bachelor’s degree in biology at Wake Forest University before pursuing his doctoral degree in Virginia Tech’s TBMH program.

The NIH funding supports travel to conferences, training, and mentorship.

“Receiving this fellowship is a great honor and puts me on a good path to achieve my career goals by helping me accumulate new skills across an array of neuroscientific approaches,” Patel said. “I’d like to thank Dr. Michael Fox, Dr. Konark Mukherjee, and Dr. Daniel English for their mentorship and training, as well as my recommenders, Dr. Leslie LaConte, Dr. Alexei Morozov, Dr. Michelle Olsen, and Dr. Matthew Fuxjager.” 

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