Eric Beyer, Ph.D., M.D.

My laboratory is investigating the process of intercellular communication; our specific goal is a molecular understanding of the structure and function of gap junctions. Gap junctions are the specialized plasma membrane structures that contain low resistance channels linking adjacent cells. In excitable tissues, they permit electrical coupling; in non-excitable tissues, they permit passage of small molecules involved in metabolic support, growth control, and embryogenesis. They may also facilitate drug metabolite delivery between cells. Gap junctions are encoded by a family of subunit proteins called connexins which are related in their transmembrane and extracellular regions, but which have unique cytoplasmic domains. Connexin-specific sequences confer different physiologic channel properties or regulation. Mutations of connexins have been associated with a number of diseases including non-syndromic deafness, Charcot-Marie-Tooth disease (neuropathy), cataracts, oculodentodigital dysplasia, and skin diseases.

In vitro expression studies and transgenic mouse studies are being used to examine the consequences of disease-associated connexin mutations.

The transfection of communication-deficient cells with connexin sequences (or expression of in vitro transcribed connexins in Xenopus oocytes) has demonstrated connexin-specific channel properties, permeabilities, and regulation. Site-directed mutagenesis is being used to identify sites within the connexins important in determining gating and permeability properties. We are also studying the sequences involved in oligomerization and cellular trafficking.

We are using adenoviruses to express connexins in endothelial cells and other mature cell types to examine the roles of intercellular communication in these cells. We are using in situ hybridization to study the roles of connexins in embryonic development. We are examining the role of connexins and intercellular communication in cell viability and apoptosis.