Mechanisms of Signal Transduction in Neuronal Differentiation and Olfaction

      Our laboratory is interested in the process of neuronal development and in neurodevelopmental disorders. We use the olfactory receptor neuron as a model for these studies. Specifically, we use molecular, cellular, and biochemical techniques to determine the role of factors, such as neuropeptides and neurotrophins, in olfactory receptor neuronal development and differentiation. The olfactory receptor neuron is the only neuron to show postnatal regenerative capacity. Therefore, it becomes an excellent model for the study of neuronal regeneration following injury or trauma. Its linear and well-organized projections to the olfactory bulb, where the primary synapses occur, is a useful system for studying processes of axonal outgrowth as well.

     Our recent studies have focused on the role of cAMP, IP3, and cGMP signaling cascades on neuronal development and differentiation. We are currently investigating the mechanisms by which various signals are integrated during neuronal development to affect neuronal survival maturation. In particular, we concentrate on the guanylyl cyclase family of transduction enzymes, as they are highly expressed in olfactory receptor neurons.

     More recently, we have begun to use olfactory biopsies obtained from humans as a diagnostic screening tool to evaluate disorders of neuronal development. In particular, we have studied the pathophysiology of Rett Syndrome, a presumed genetic disorder which produces profound retardation and autistic features in female children. We intend to extend this study to autism and neurodegenerative diseases.