Elizabeth Engle is studying the development of cranial nerves and defining genetic disorders that perturb their normal development in humans and model organisms.
Characterizing Human Disorders of Axon Guidance
The human brain is highly organized and contains a myriad of axon tracts that follow precise pathways and make predictable connections. Model organism research has provided tremendous advances in our understanding of the principles and molecules governing axon growth and guidance. Remarkably, however, only a handful of human disorders resulting from primary errors in these processes have been identified. My lab has identified and characterized a series of congenital eye movement disorders that are inherited as Mendelian traits and found that they result from primary defects in axon guidance. We have used genetics to identify these underlying disease genes and have identified mutations that alter genes encoding an axon guidance receptor, cell signaling molecule, kinesin anterograde motor, and microtubule cytoskeleton. We have now introduced a series of these causative mutations into mice to study the resulting neuropathology. The student will have the opportunity to learn how we define these disorders anatomically and to participate in studies to define the axon guidance defects at a cellular and molecular level.
Identification of Human Neurodevelopmental Disease Genes
We study congenital disorders of eye and face movement by first defining their genetic etiologies. Discovering the genetic cause of an orphan disorder can provide a starting point to uncover the underlying molecular pathogenesis and may lead to new therapeutic approaches. The student will learn how to use SNP (single-nucleotide polymophism)-based mapping of disease genes and interpretation of next-generation exome and whole-genome sequence data to identify new human disease genes.