Dr. Bruce Appel Lab (Research on neural development, myelination, stem cells "Genetic Basis of Childhood Neurological Disorders". 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 devestating disorders called leukodystrophies and are also implicated in brain injury resulting from premature birth and neuropsychiatric disorders such as autism. We use zebrafish as a model systm because the small size, transparency and external development of the embryos permit us to directly observe behaviors of neural cells using time-lapse photomicroscopy. To discover the genes necessary for neural development, which might be targets for regenerative therapies, we screen for mutations that cause defective nervous system development. 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, oncologists and human geneticists.
Dr. Emily Bates Lab (Research on neural and craniofacial development) "Animal Models of Migraine and Fetal Alcohol Syndrome". It has long been known that prenatal exposure to alcohol can cuase cognitive impairment and increased incidence of physical birth defects, including abnormalities in facial features. The Bates lab has identified a potential therapeutic target for fetal alcohol syndrome by studying a rare genetic disorder that has the same spectrum of congenital birth defects and which is caused by genetic disruption of a potassium channel. This potassium channel controls the gradient of ions across the cell membrane. The same potassium channel is blocked in the presence of alcohol. The Bates lab now explores the possibility that the activity of the potassium channel can be modified to prevent the devastating affects of alcohol on a developing baby. The Bates lab also studies migraine and how it occurs using clues from human genetics. She has developed a mouse model and is using this to test potential therapties (her studies were recently highlighted on National Public Radio (NPR).
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. Lee Niswander Lab (Research on neural development) "Genetic Basis of Neural Tube Defects and Neuromuscular Disorders". The neural tube is the embryonic beginning of the brain and spinal cord. Failure to complete neural tube formation during the first weeks of pregnancy results in the very common birth defect called a neural tube defect (NTD), which includes spina bifida and anencephaly. The Niswander lab has created mouse models of NTDs and uses these to discover numerous novel genes that control the process of neural tube formation. Her lab has also created unique mouse models to study how the nerves exit the spinal cord and find their way to the skeletal muscles to regulate muscle movement. These mice represent models to study human neurological diseases such as ataxia and progressive neuropathies, as well as myopathies similar to muscular dystrophies. Her lab has also pioneered methods to visualize the processes of neural tube closure and guidance of the nerves to their muscle targets. This imaging approach is now being combined with her novel mouse genetic reagents to understand how developmental processes go awry in these models of human NTDs and neuromuscular diseases to better understand how to treat and prevent these disorders. Finally, her research explores the influence of environmental factors to alter the severity of these developmental defects. This has led to a patent application for biomarkers of a human myopathy and a novel therapy to help ameliorate muscle weakness.
Dr. Julie Siegenthaler Lab (Research on neural development) "Development of Brain Blood Vessels and Pediatric Stroke". The brain is in constant need of nutritive blood flow, which is provided by a dense, complex network of blood vessels. Interruption of blood flow to the brain, which occurs during stroke, can cause permanent disability or death. This critical support system for brain growth and function is formed during fetal development when blood vessels grow into and expand within the brain. The focus of the Siegenthaler lab is to understand the complex series of cellular and molecular cues that control growth, maturation and stability of the brain vascular plexus. We are primarily interested in how signals from the maturing brain stimulate vascular growth and the nature of the communication between blood brain vessels and closely adjacent support cells, called pericytes. It is hoped that understanding the important events and players in blood vessel development will ultimately reveal novel therapeutic avenues to prevent or ameliorate the severity of stroke in both pediatric and adult populations. Our lab has developed a number of mouse models in which we can alter different steps of brain vascular development. Integral to our analysis of these developmental events in the mouse brain are advanced microscopy techniques, including time-lapse imaging and confocal microscopy. With these techniques we hope to visualize, in real-time, the interactions of newly forming blood vessels with the neural environment.