Gap Junctions

Understanding Selective Intercellular Communication

Gap junctions allow neighboring cells to directly exchange electrical and biochemical signals, yet the molecular rules governing selective communication between cell types remain poorly understood. Our lab studies how the 21 human connexin isoforms assemble into distinct channel architectures and how these interactions shape the transfer of ions, metabolites, and signaling molecules across tissues.

A major focus of our work is understanding channel specificity, why certain connexin isoforms readily interact while others remain incompatible, and how these molecular preferences ultimately define cellular communication networks in complex tissues. To address these questions, we developed FETCH (Flow Enabled Tracking of Connexosomes in HEK Cells), a quantitative assay platform that enables systematic mapping of connexin compatibility and gap junction docking interactions across isoforms. Using FETCH alongside imaging and functional assays, we investigate how selective intercellular coupling contributes to physiology in the nervous system and beyond, and how disrupted connexin communication drives disorders including epilepsy, deafness, neurodegeneration, and cancer.

Gap Junction Assembly and Dynamic Remodeling

Gap junctions are highly organized and dynamic cellular structures composed of thousands of individual intercellular channels assembled into large membrane plaques. Our lab studies how these structures form, reorganize, and internalize, with particular interest in the hierarchical assembly of gap junction complexes and the mechanisms governing their remodeling.

We investigate how connexin composition influences plaque organization, how fully docked channels are internalized into specialized double membrane vesicles called connexosomes, and how these processes regulate intercellular signaling and tissue homeostasis. By combining live cell imaging, flow cytometry, and molecular engineering approaches, we aim to uncover fundamental principles governing the maintenance and regulation of cellular communication.

Programming Cellular Connectivity

Our lab uses the principles of gap junction interaction, compatibility, and remodeling that we uncover to design new ways to control communication between cells. We develop three major classes of communication modulators: engineered gap junctions that selectively couple defined cell populations, isoform specific gap junction inhibition tools, and tunable gap junctions and hemichannels with altered functional properties.

These systems allow us to selectively introduce, block, or reshape cellular communication pathways in complex biological environments. By combining protein engineering, quantitative screening, and functional assays, we aim to create new tools for studying intercellular signaling and developing targeted therapeutic strategies.