Bruce J. Nicholson, Ph.D.

Research

Our laboratory is interested in defining the structure and properties of the unique class of membrane channels called gap junctions that allow the direct passage of ions, small metabolites and secondary messengers between cells. The proteins that comprise these channels, a family called connexins in the vertebrates, are diverse in nature, with multiple members of the family being expressed in most cells and tissues. It has become increasingly evident that this diversity in connexin composition imparts differential regulatory and permeability properties to these intercellular channels. Evidence that structural diversity has physiological consequences is provided by the linkage of five very distinct human diseases to defects in different connexin genes. Specifically, deafness is linked to Cx26 and Cx31 mutations, a form of skin keratinopathy is linked to distinct defects in Cx31, peripheral neuronal degeneration in Charcot Marie Tooth’s disease is linked to a plethora of Cx32 defects and cataracts are linked to Cx50 defects .The long-term aim of these studies is to better understand the biological role played by gap junctions in different systems. A particular focus is the mechanism by which gap junctions act as tumor suppressors. As part of these studies, we are comparing the permeability of connexins that have proven to be effective growth suppressors, to those that are not. We have also been investigating the mechanism through which some oncogenes (e.g. v-src) can inhibit coupling.