Dept.: Professor, Department of Pediatrics and Seattle Children’s Research Institute-Center for Integrative Brain Research
Neuroscience Focus Groups:
We are interested in the genetic and developmental basis of structural birth defects of the brain both in humans and mice. We have a specific interest in malformations of the cerebellum, a brain structure that lies between the brainstem and the cerebrum and plays important roles in sensory perception, motor output, balance and posture in addition to cognition and emotion. The relative anatomic simplicity of the cerebellum makes this important brain structure an ideal system to study neural development. Further, the mechanisms that drive cerebellar development are shared by more complex regions of the brain, including the cerebral cortex. Together with Dr. William Dobyns, we maintain the world’s largest clinical database of human cerebellar malformation patients. These birth defects cause neurodevelopmental delays and contribute to Autism. Our resource has enabled us to find the genes that cause these relatively common, yet poorly understood birth defects. In parallel we are also studying mutant mice with cerebellar and other brain malformations to 1) understand how brain malformations arise during development and 2) decipher basic developmental mechanisms that regulate normal brain development. One of our major findings from these studies is that posterior skull development and cerebellar development are fundamentally interdependent. Signals from the developing skull are essential to regulate development of the adjacent cerebellum. Ongoing experiments in the lab are aimed at identifying these signals and their downstream molecular pathways as one means of finding additional human disease causative genes. Finally, Dr. Millen’s group is working on mouse embryonic stem (ES) cell technology to more efficiently and rapidly generate mouse models of human genetic disease. By combining the power and strengths of both mouse and human genetics, our studies are leading to a more comprehensive understanding of the basic biology and genetics of neurodevelopmental disabilities.