Randall Reed Ph.D
Professor of Molecular Biology and Geneticsrreed@jhmi.edu
Telephone Number: 410-955-4631
Fax Number: 443-287-7672
Johns Hopkins University School of Medicine
School of Medicine
725 North Wolfe St.
Baltimore, MD 21205
Molecular Mechanisms of Signal Transduction and Neurogenesis in the Olfactory System
The mammalian olfactory system provides an excellent model to study two of the important questions in molecular neurobiology. The continual replacement of olfactory receptor neurons mimics many aspects of neuronal differentiation and development in the brain. The olfactory system, therefore, provides a unique opportunity to observe processes in adults which, in other neuronal systems, only occur in the embryo. Additionally, the mammalian olfactory system has the remarkable ability to detect a wide variety of odorant molecules with high sensitivity and specificity. Olfactory acuity likely results from the contributions at the levels of anatomy, cellular structure and organization, biochemistry, genetics and neuronal connectivity. My laboratory has used biochemical and molecular genetic techniques to examine the mechanisms underlying development in the olfactory system, as well as the processes responsible for odorant detection. These studies have revealed an important role for genetic specialization in the olfactory system.
A major current effort in the laboratory focuses on the mechanisms that determine the patterns of expression of individual odorant receptor genes within the epithelium and the mechanism which control the pathways and eventual target cells chosen by those receptor neurons. We have identified transcription factors that likely coordinate the expression of key components in the outgrowth of neurons in mammals and C elegans. We have studied the mammalian olfactory system to elucidate the contributions of biochemistry, genetics and neural connectivity to sensitivity and specificity in olfactory signal transduction. We are continuing to characterize the molecular components of the second messenger pathways in olfactory and non-olfactory system. Major future directions will include the characterization of transcriptional activators that play a central role in neuronal differentiation. Finally, the molecular cloning of components of the olfactory signal transduction cascade, especially the receptor protein genes, has provided the essential tools to examine the processes which define the connections the olfactory neuroepithelium and the brain. Recently, we have developed systems to express olfactory receptors in heterologous systems and determined ligands that activate several members of the family. Combined with other approaches in our laboratory, we hope to elucidate the principles of olfactory coding and odorant perception.