For more than 20 years, Soo and Jae W. Lee have studied the specialized functions of transcription factors including FOX proteins, a family of 40-plus genes integral to the lifetime development and function of such organs as the brain and heart.
With expertise in neurodevelopment, Soo Lee, Ph.D., a professor of pediatrics in the OHSU School of Medicine and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital, was drawn to FOXG1’s influence on brain growth and function, and the role it plays in rare neurological syndromes that impact human communication, mobility and sleep.
Unbeknownst to Soo, what started as an idea for an interesting scientific experiment would ultimately inspire her life’s work.
In January 2010, the Lees welcomed their first child, a beautiful baby girl with dark hair and eyes. They named her Yuna.
“She was perfect,” said Jae W. Lee, Ph.D., a professor of pediatrics in the OHSU School of Medicine and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital. “We knew that she would be an incredible addition to the world.”
As she grew, Yuna experienced frequent seizures, difficulty sleeping and periods of inconsolable crying. At age 2, she could not sit up, stand, walk or speak.
Following multiple discussions with colleagues within their respective scientific circles, Soo and Jae received the news they suspected and dreaded. While the odds were staggering, genetic testing confirmed that Yuna had a mutation in one copy of her FOXG1 gene.
Approximately 350 people worldwide have been diagnosed with FOXG1 syndrome, or FS. While medications and therapies are available to help manage symptoms, currently no treatment or cure is available.
“As both a scientist and a mother, I needed to better understand how Yuna’s brain works,” said Soo. “I wanted to discover a pathway for treatment to help my daughter.”
Using a mouse model, Soo and a team of scientists at OHSU and the University of California, Santa Cruz, set out to determine how the corpus callosum, a thick band of nerve fibers that allows communication between the left and right sides of the brain, is constructed during fetal development.
The results, recently published online in the journal Neuron, revealed the corpus callosum missing one copy of FOXG1 appeared thinner and shorter compared with that of a typical brain. This change likely reduced communication across the brain’s hemispheres.
Furthermore, while it was previously understood that the presence of FOXG1 within stem cells helps to facilitate proper brain formation, the scientists also demonstrated similar FOXG1 traits within neurons.
“Our findings confirm that two copies of the FOXG1 gene within the brain’s neurons are critical to the proper development and mapping of the brain in utero,” said Soo. “This gives us a better understanding of Yuna’s impaired brain structure, as well as a starting point for future research.”
Although more research is needed, Soo believes these findings will facilitate downstream treatments that may help repair some FS symptoms in human patients.
“It gives me hope for Yuna, as well as the hundreds of others living with FS,” said Soo. “The ability to better understand my daughter’s condition inspires me to keep moving forward. I am a more optimistic scientist because of her.”
This research was supported by the National Institute of Neurological Disorders and Stroke (grants R01NS054941, R56NS054941, R01NS100471, R01NS089777and P30NS061800, the National Institute of Diabetes and Digestive and Kidney Diseases (grants R01DK064678 and R01DK103661) and the National Institute of Mental Health (grant R01MH094589), all components of the National Institutes of Health; the American Heart Association; the Blackswan Foundation; and the FOXG1 Research Foundation.