Department of Neuroscience
Professor in the Department of Neuroscience
Department of Neuroscience
190 Rightmire Hall, 1060 Carmack Road
Research Lab: Beattie Lab
Research Area: Genetic and molecular analysis of motoneuron development with an emphasis on the motoneuron disease spinal muscular atrophy.
Current Research: Our goal is to understand the genetic and molecular programs that facilitate motoneuron axon, dendrite and synapse formation. These processes are essential for motoneuron function and if they do not occur correctly will compromise movement. Because zebrafish have a well-characterized nervous system and relatively simple neuromuscular organization, they are an excellent vertebrate model organism for these studies.
Spinal muscular atrophy (SMA) is a devastating motoneuron disease that effects infants/children leading to paralysis and early death. Approximately ~1/10,000 babies a year are affected with a carrier rate of ~1/50. SMA is caused by a deficiency in the survival motor neuron (SMN) protein. Although SMA is primarily a motoneuron disease, it remains unclear how low levels of SMN leads to motoneuron dysfunction and loss. Our zebrafish studies have conclusively demonstrated that SMN is essential for normal motoneuron development. To elucidate the critical function(s) of SMN in motoneurons, it is imperative to determine how it is acting during motor axonal outgrowth and arborization, dendrite formation and neuromuscular junction (NMJ) formation. If motoneurons do not undergo these key development events with fidelity, they are set up to fail and will have functional deficits leading to muscle weakness and paralysis. This would have profound implications for therapeutic strategies stressing the need to start treatments are early as possible for this disease. Our research program focuses on elucidating the function of SMN that is critical during motoneuron development. Current research from our lab suggests that SMN interacts with RNA binding proteins important for RNA transport in developing axons and dendrites. Using a combination of genetics, biochemistry, and imaging we are investigating whether disruption of SMN and these complexes leads to motoneuron defects consistent with SMA.
Research Techniques: Genetics, in vivo imaging, biochemistry, RNAseq, cell biology
PI: Spinal Muscular Atrophy: Is it a motor axon disease? 7/10-6/16, NIH/NINDS R01
PI: Survival Motor Neuron (SMN) function in motoneuron development, 9/23/15-9/22/16, NIH/NINDS R56 (bridge funding)
PI: Identifying the initial mechanisms of nervous system dysfunction in fALS, 8/12-7/16, ALS Association
Co-PI: Evaluation of novel γ-secretase modulators in a zebrafish ALS model, 8/14-7/16, ALS Association
Degree: Case Western Reserve University, PhD, 1992
Postdoctoral Training: University of Oregon, Dr. Judith Eisen, 1992-1997