Mona C. Buhusi

Biography

Understanding the pathogenesis of neuropsychiatric disorders in which neuronal wiring is abnormal, such as mental retardation or schizophrenia, and the first step towards the development of new therapies that would help neuronal rewiring after various insults or after neuronal grafting. Brain function relies on the precise wiring of neurons during embryonic development, when newly generated neurons migrate to their appropriate location, extend axons and form synapses onto their targets. To generate appropriate neuronal circuits, axons respond to various attractive or repulsive cues, from extracellular matrix components to diffusible or cell-anchored guidance molecules. Cell surface receptors for these guidance molecules collaborate or compete to elicit specific cellular responses such as endocytosis, actin remodeling, modulation of microtubule dynamics, and protein synthesis, transport, or degradation. Elucidating these mechanisms is crucial for understanding the pathogenesis of neuropsychiatric disorders in which neuronal wiring is abnormal, such as mental retardation or schizophrenia, and the first step towards the development of new therapies that would help neuronal rewiring after various insults or after neuronal grafting. My research aims at (a) identifying the specific sets of guidance cues along individual pathways, able to direct one particular group of axons to the corresponding target neurons, (b) understanding how the complex interactions between diverse axonal membrane proteins and their ligands result in specific cellular decisions along the path, and (c) understanding how anomalies in neuronal connectivity relate to human neuropsychopathology. To achieve these goals, my research involves techniques from molecular biology, protein biochemistry, neuronal cell culture, neuronal tracing, histological and immunostaining, conventional and laser confocal microscopy on fixed and live specimens, and the construction and analysis of animal models.