By Guest Blogger, Phil Ash, GRIN2B Foundation Board Member
Vacation. Hotels. Kids. Time away. These phrases evoke feelings of fun, activities, and relaxation for parents and families desperate for a break from the rat race. It’s harder for me to feel the same way. Vacations for my family are the ultimate wild card. I never know how our three kids, ages 2, 6 and 9 are going to react to a change in the routine. My wife and I have experienced getaways that swing wildly from fun to chaos, and back. Some have gone okay, others have been cut short. Not knowing how vacations are going to go or if our non-verbal daughter is going to enjoy herself are big stressors for me.
Our recent family getaway at the end of June was different. We took a 4 hour road trip from Chicago to the University of Michigan, Ann Arbor to visit the lab of Samuel Kwon, one of many GRIN2B researchers. Sam is an Assistant Professor and, according to his website, “studies mechanisms underlying neuronal dynamics and plasticity.” Don’t worry, we didn’t really know what that meant either.
We had met Sam and his wife at the GRIN2B Foundation Family Conference last year and had kept in touch ever since. My wife, Liz, our Board President, came up with the idea to combine a family vacation with a visit to the University of Michigan, and Sam graciously agreed to give our family and the Crider’s (another GRIN2B Family) a tour of his lab. For us, this was more than just an overnight trip. We were going on a journey to see first-hand, important research regarding GRIN2B-Related Neurodevelopmental Disorder. What’s more, we would be going with a built-in support system in the Crider family: Brittaney, Mike and their two kids.
During most vacations, our family is always the outlier. When things go wrong or when breakdowns occur, it can feel like we’re alone on an island. But having another GRIN2B partner family and a group of passionate researchers excited to see us calmed my anxiety and helped create a great getaway for everyone in our family. Like dorks, every member of our two families wore our GRIN2B t-shirts. Everywhere we went, people asked us questions about our “bee” shirts.
Our two families arrived at the University of Michigan and were met by Sam’s undergraduate research assistant (also named Sam!) who took us to the lab. Sam and his assistant gave us a brief presentation regarding their work and then took us on a tour of their impressive, extensive laboratory.
If I’m being honest, the minutiae of what Sam is doing was well over my head, and for good reasons. The research presentation was given in a small conference room with 5 children all under the age of 9; including our 2-year-old son who spent his time running around doing 2-year old things! In spite of the distractions, I was humbled by their passion and excitement to see us. Their PowerPoint presentation included citations from our website, www.grin2b.com. This may not seem like a big deal, but as an educator who recently finished his Masters Degree, it was so satisfying to see a group of brilliant researchers citing a website I helped create. The lab was extensive and it was a bit strange actually seeing the research mice. (Don’t worry – we’ll share more specifics about Sam’s lab towards the end. Keep reading!)
Sam and his family could not have been more gracious and patient with us. They were excited to speak with us and spend time with our families. Following the tour, they took us to lunch. After we bid them goodbye, the balance of the day was our own. Our family and the Criders went to a children’s indoor playground, had pizza in the hotel and then spent some time with the kids by the pool. Normal family stuff, but for me, this time it was free from the usual anxieties. Our kids behaved wonderfully, but having another family with us that also experiences the highs and lows that come with a GRIN2B diagnosis made all the difference.
Hopefully, this was just the first of many research road trips we will take!
If you were thinking you’ve heard of Sam Kwon before, it’s probably because he recently became GRIN2B Foundation’s Science Director! We were so impressed with his passion and expertise at our visit and knew we’d finally found the missing piece of our organization. Our Board was thrilled to offer him the position earlier this month, and he is already more than proving this worth by organizing our first grant cycle. Read Sam’s bio here http://grin2b.com/medical-advisory-board/
Between the science being over our heads and having to wrangle 5 children, ages 2-9, none of us adults were really able to take notes during this visit. We thought it was best for Sam to explain his work himself so here are his answers to our follow-up questions:
Samuel Kwon, PhD
How long have you worked for the University of Michigan? Tell us a little bit about your lab.
I have been working at the University of Michigan since January 2018. That is when I started my own lab after several years of postdoctoral research at Johns Hopkins. The research in my lab focuses on how nerve cells in the brain process sensory information and how this process is altered in humans carrying mutations in autism-related genes. My lab is especially interested in how brain cells change over time as a new knowledge or skill is learned. This is called ‘neural plasticity’. We leverage the fact that mammalian brains are similar across species and use mice as a model organism to study neural plasticity in the cerebral cortex of health and disease. We can train mice to perform simple behavioral tasks while monitoring and manipulating individual brain cells using state-of-art microscopic tools.
How did you become interested in studying GRIN2B?
In April 2018, I had the privilege to attend the scientific meeting organized by Simons Foundation, which provides a major support for my current research. The meeting was heavy on genetics of different neurodevelopmental disorders. Although I am not a geneticist, it was obvious to me that a set of genes required for proper signaling between nerve cells were strongly linked to various neurodevelopmental conditions. Grin2B was consistently one of them, but I didn’t look into it any further. Two months later, my wife and I found out that her 3.5-year-old nephew in South Korea had been diagnosed as having a Grin2B neurodevelopmental disorder. It took three years to find out since the time where his parents first started noticing severe developmental delays such as motor deficits and intellectual disability, because a Grin2B mutation is extremely rare in South Korea or anywhere in the world. To connect with other GRIN2B families, I attended the first GRIN2B Foundation Family Conference in September 2018. It was an invaluable experience for us at both personal and scientific levels. By talking and listening to other families, I learned a lot about the challenges that GRIN2B parents face daily as well as practical tips that could improve the quality of life of both parents and their children. The conference included research presentations by world-renowned neuroscientists. Inspired by these presentations, I decided to launch a research project in my own lab to investigate how Grin2B mutations impact neural circuits in the brain.
Tell us (in layman’s terms) about your work on GRIN2B.
A common hallmark of children with GRIN2B neurodevelopmental disorders is a motor dysfunction. We aim to understand how variations in GRIN2B impact the neural circuit for motor function using mouse models of GRIN2B variants. Specifically I will focus my effort on determining the time points when therapeutic interventions for motor dysfunction need to be focused. From there, I will expand our research directions toward a better understanding of how Grin2B mutants contribute to specific pathological hallmarks including sensory and cognitive impairments. We hope that this research would accelerate the availability of treatments for Grin2B-related syndrome.
What do you hope to learn from your mouse models?
We have been using a mouse model in which the level of GRIN2B can be reduced in specific brain cell types. This is called a ‘conditional knock-out’ mouse. I obtained this model from Professor John Gray at UC-Davis. One of the experiments being performed in my lab is to reduce GRIN2B in different areas of cerebral cortex and test its impact on motor function. In parallel, we are creating a ‘conditional rescue’ mouse in which GRIN2B can be switched on in specific brain cell types by the experimenter, at any point in time throughout development. With these resources, we would be able to experimentally modulate GRIN2B in specific brain areas at different time points and monitor its effects on behavior and brain function in living mice. These efforts will enable us to determine if there is a ‘critical period’ in which a normal level of GRIN2B is essential and will provide an important scientific framework for therapeutic approaches.