Dr. Bruce Appel Lab We investigate how the nervous system is formed during development with the expectation that this will help us better understand the basis of neurological diseases that affect children and lead to better treatments of those conditions. Our primary focus is on formation of myelin, which functions as insulation on nerves. Defects in myelination result in devastating disorders called leukodystrophies and also are implicated in brain injury resulting from premature birth and neuropsychiatric disorders such as autism. We use zebrafish as a model system because the small size, transparency and external development of the embryos permit us to directly observe behaviors of neural cells using time-lapse photomicroscopy. Our current studies are advancing knowledge of mechanisms that maintain neural stem cells and direct myelination. Our work is enhanced by productive collaborations and interactions with pediatric neurologists and human geneticists.
Dr. Emily Bates Lab Dr. Emily Bates’ lab uses genetics to determine the molecular mechanisms of pediatric disorders. Research in her lab has identified the mechanism by which mutations that disrupt an ion channel lead to cleft palate, small jaw, skull defects, and other craniofacial abnormalities. These abnormalities are similar to those that are associated with fetal alcohol spectrum disorder (FASD) and alcohol binds and blocks the ion channel suggesting that inhibition of ion channels could lead to the morphological differences associated with FASD. The Bates lab also use mutations that were found in human patients with severe brain malformations to understand the mechanisms by which the cytoskeleton is regulated to dictate neuronal architecture and ultimately brain development.
Dr. Santos Franco Lab (Research on neural development) The cerebral cortex is the control center of most of our higher-level brain functions, including thought, language, memory and emotion. During cortical development, billions of neurons must be precisely specified and assembled into the intricate circuits that underlie these complex tasks. Disruption of this process is associated with many devastating human neurological disorders, including epilepsy, schizophrenia, autism and mental retardation. The long-term goal of my lab is to define the cellular and molecular mechanisms that control development of neural circuits in the cerebral cortex and to understand how defects in this process lead to brain dysfunction.
Dr. Julie Siegenthaler Lab The brain is in constant need of nutritive blood flow and protection from physical, chemical and pathogenic insult. These needs are met by a network of blood vessels that feeds the brain, the blood brain barrier (BBB) and the meninges that surrounds the brain and spinal cord. Our lab is interested in the complex interplay between the brain and these critical support structures during development, in the adult brain and their breakdown in disease. Our development projects focus on key signals exchanged between the developing brain, the forming meningeal layers and the growing vasculature that ensure correct formation and maturation of these structures. We are interested in the role of key developmental signals such as retinoic acid and WNT-β-catenin signaling. Breakdown in these support structures, in particular the BBB and vascular integrity, occurs in many CNS diseases. We apply our knowledge and tools developed to study BBB development and vascular growth to elucidate mechanisms that cause brain vascular disease pathology in ischemic stroke and encephalitis. We address these important questions using mouse genetic tools to manipulate specific cell types in the brain, meninges or vasculature during development and in specific disease models.