Finding the Underlying Causes of Neurodevelopmental Disorders
Few treatments are available for people born with autism and other neurodevelopmental disorders. A large part of that is not understanding the underlying biological mechanisms leading to the disorders. But by finding the cause, Sameer Bajikar, PhD, hopes to create a foundation that will lead to more effective options to improve the lives of these children.
Here, Bajikar shares the potential applications of his work and why it's so important.
Sameer Bajikar, PhD - Understanding the mechanisms in childhood neurodevelopmental disorders.
Samir Bajikar: So I love being a researcher because I get to use my creativity to study the underlying biology of childhood neurodevelopmental disorders. And as part of being a researcher, I get to work as a team with other individuals to be able to design experiments and make new discoveries that can help improve the lives of these children.
Samir Bajikar: My name is Samir Bajikar, and I'm an assistant professor of cell biology and biomedical engineering. My lab uses a combination of cell models, animal models, and computational biology to try to understand more about the underlying mechanisms that go awry in childhood neurodevelopmental disorders.
Samir Bajikar: Children with neurodevelopmental disorders like autism spectrum disorder and intellectual disability have very few treatment options available to them currently. Our lab is studying these diseases using a number of different tools to help understand the underlying biology that may be going awry. And by understanding those processes, we hope to develop therapeutics and drugs that can help correct those processes and have these children lead healthier lives.
What are you working on right now?
I am working towards understanding the underlying molecular pathways that go awry in childhood neurodevelopmental disorders. I am specifically interested in disorders caused by mutations in single genes.
For some genes, mutations that decrease protein function or increase protein levels cause a neurodevelopmental disorder. These so-called “Goldilocks” genes require precise expression for normal brain function. One example of a Goldilocks gene is methyl CpG binding protein 2 (MECP2). Mutations that break MECP2 function cause Rett syndrome, while genomic duplications of MECP2 cause MECP2 duplication syndrome — both are severe neurodevelopmental disorders characterized by intellectual disability, motor dysfunction, and seizures.
Interestingly, both Rett and MECP2 duplication syndrome symptoms can be reversed when the MECP2 dosage is correct in preclinical models. My research investigates what biological events occur during the process of the Rett or MECP2 duplication syndrome brains “fixing” themselves. To tackle this challenge, we're using human neuronal models, animal models, and high-throughput molecular measurements.
What are the most intriguing potential clinical applications of your work?
Rett syndrome and MECP2 duplication syndrome are just two examples of reversible, single-gene disorders. We've identified many other neurodevelopmental disorders that display this phenomenon. However, the underlying mechanisms of reversing the disorders remain unknown. Understanding the important pathways to restore brain function across multiple disorders could reveal a common set of genes or pathways that could be used to develop therapies that impact multiple disorders.
What recent discovery/paper/presentation has impacted the way you think?
I was very excited by the paper recently published by Lacoste et al. in Cell (PMID: 39353438). In this paper, they found that many (nearly 20%!) pathogenic mutations found in humans cause the mutated protein to localize to the wrong part of the cell. So we have to consider not only how a given gene mutation may affect the stability and levels of that protein, if it affects a key domain required for normal function, but we also have to consider how that mutation alters where the protein normally resides in the cell.
What made you choose UVA Health as the place to do your research?
UVA Health is an incredible place to do research because of the breadth and depth of expertise throughout Grounds. Additionally, UVA is so collegial and collaborative, making it easy to work with experts from disparate fields to make true innovations. Furthermore, UVA has invested heavily in neuroscience and biomedical research, making this an exciting time to start a lab at UVA and take advantage of the momentum. Lastly, I am a Double Hoo having received my BS in 2010 and PhD in 2016 in Biomedical Engineering from UVA. It’s great to be back at UVA and Charlottesville!
What do you wish more people knew about your area of research?
Though many neurodevelopmental syndromes are rare, the biological lessons we uncover from researching rare diseases inevitably play a part in more common diseases.
How did you become interested in your area of research?
My wife is an elementary school teacher who has had students with neurodevelopmental disorders. I am motivated by the struggles the children face in their daily lives due to symptoms of their disorders. I am also humbled by the perseverance and strength displayed by the children and their families as they navigate everyday life. I want to apply my research efforts towards improving the lives of children with neurodevelopmental disorders.
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