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Home > Research > Larry Fromm
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Larry Fromm, PhDAssociate Professor Research InterestsThe research in my lab focuses on the mechanisms that control formation of the neuromuscular synapse. Molecules that are secreted by and exchanged between nerve and muscle cells function to send messages between these cells that determine when and where synaptic connections form. In response to these signals, intracellular signaling pathways are activated that ultimately lead to formation of specialized synaptic components both on the presynaptic side, in the nerve, and on the postsynaptic side, in the muscle.One of the defining features of the postsynaptic apparatus is the high density of acetylcholine receptors (AChRs) located in the small region of the muscle fiber membrane that is adjacent to the nerve terminal. The mechanisms by which AChRs become concentrated in this region have been studied in order to understand the signaling pathways that mediate synapse formation. There appears to be two distinct mechanisms for localizing AChRs: redistribution of AChR proteins within the muscle fiber membrane to the synaptic region and selective transcription of the genes encoding AChR subunits within the few muscle nuclei that are situated at synaptic sites. A current focus of the lab is on the intracellular signaling mechanisms by which muscle cells respond to synaptic signals to induce a transcriptional response. For these studies, we typically use cultured muscle cells in which we add extracellular signaling molecules that mimic signals received at the synapse. Using this system, we have identified particular gene regulatory sequences required for mediating a transcriptional response to synaptic signals. These regulatory sequences serve as binding sites for particular transcription factors that might be signaling targets, and we have identified transcription factors that bind to these sequences. We are determining how these factors are regulated by signaling at synapses and how they act to induce transcription. One way that transcription can be regulated is by modification of chromatin structure. We are studying how chromatin structure is altered in response to synaptic signals and how particular transcription factors might mediate these alterations. By studying these signaling mechanisms, we hope to better understand the molecular interactions between nerve and muscle cells that are responsible for forming the neuromuscular synapse, which may have relevance to certain diseases such as muscular dystrophy. Representative publications:
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