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For the last 20 years, Sam’s research has focused on understanding the molecular mechanisms that underpin the ability of spinal motor neurons to acquire their identity among highly diversified neuronal cells. He has also explored how motor axons are correctly connected between the spinal cord and the muscle during embryonic development. More recently, Sam has been investigating their use as therapy for Amyotrophic Lateral Sclerosis (ALS) — or Lou Gehrig's disease.

Sam has published more than 83 research articles — many of these have appeared in such top journals as Cell, Nature, Science, Neuron, Nature and Neuroscience. He serves as ad hoc reviewer of numerous peer-reviewed journals, including the top journals mentioned above, and sits on several grant review committees. Sam is also on the editorial board of several journals and served as editor-in-chief of Molecular and Cellular Neuroscience.

He has received numerous awards, including the McKnight Scholar Award in Neurobiology, the Whitehall Foundation Scholar Award, the March of Dimes Basil O’Connor Scholar Award, the Alfred P. Sloan Research Fellow Award, the PEW Scholar Award, and The Helen McLoraine Developmental Chair in Neurobiology.

Sam is particularly interested in how motor neurons develop and make connections between the spinal cord and muscles in the body during fetal development, since these connections are necessary for all body movements. Spinal cord injuries lead to paralysis because motor neuron function is disrupted. Degenerative diseases such as ALS (Lou Gehrig's disease), spinal muscle atrophy and post-polio syndrome result from the loss of motor neurons. Sam's goal is to understand the fundamental principles that control the specification and connectivity of spinal neurons involved in locomotion, particularly motor neurons. Over the long term, these studies should provide insight into the basic principles involved in the proper formation of the nervous system, as well as provide practical information for treatments of spinal cord injury and diseases like amyotrophic lateral sclerosis, post-polio syndrome, and spinal muscle atrophy. The approaches used in his lab include experiments with genetically modified mice, developmental studies with chicken embryos, and differentiation assays with ES cells. Currently his lab has three areas of investigation: the mechanisms that control gene regulation during neuronal fate specification, the analysis of axon guidance, and studies of the central pattern generator circuitry involved in locomotion.