Research Professor, Surgery
Professor, Physiological Sciences - GIDP
Research in Dr. Burt's laboratory over the last 30+ years has centered on the mechanisms underlying connexin- and gap junction-mediated coordinated tissue function and controlled growth, with particular emphasis on vascular function in injury and disease settings. Originally, the contribution of gap junctions to controlled growth was assumed to reflect their abilities to mediate intercellular exchange of growth related molecules including metabolites, nucleotides and other signaling molecules; however, in recent years it has become clear that connexins contribute to controlled growth through mechanisms independent of formation of functional gap junction channels. These mechanisms include formation of functional hemichannels, interactions of connexins with elements of the cell cycle machinery, and even with transcriptional machinery. In ongoing studies we are testing the general hypothesis that phosphorylation-dependent and connexin-specific differences in the permselective properties of gap junctions and the abilities of connexins to participate in protein-protein interactions provides vascular cells strategies for maintaining electrically coordinated contraction/relaxation functions while simultaneously providing vascular cells a “molecular switch” that supports transition of these cells between proliferative and quiescent states.
Over the years 10 post-doctoral fellows have worked in Dr. Burt's group, 8 PhD students have completed their dissertation studies in her laboratory, and two PhD students are currently in training; most of these trainees have derived support from the training grant that she has directed since 1992. In addition to these trainees, multiple PhD, masters, and undergraduate students have worked in her laboratory; most of these students have continued their education in professional schools (Medical, Osteopathy, Public Health and Pharmacy) or PhD programs, and continue to integrate research into their ongoing professional careers.
Gap junction channels and their comprising proteins, the connexins, support the coordinated function of virtually all tissues of the body. In the heart and blood vessels, they are necessary for coordinated contractile function; compromised function of this intercellular communication pathway predisposes the heart to arrhythmias and the blood vessels to vasospasm. These channels and proteins also support tissue homeostasis by serving as integral members of intracellular signaling cascades active during development, and in response to acute injury and chronic disease. In these latter settings, the channels and/or proteins are of central importance in regulating cell cycle progression and therefore cell proliferation. Of the twenty genes encoding connexins in the human genome, four (Cx37, Cx40, Cx43, Cx45) are common to cells of the cardiovascular system. The unique contributions of these connexins to cell and tissue function in response to growth factors and tissue injury are studied in the Burt Lab. We use cell and animal models for our studies. Molecular approaches are used to introduce specific connexin proteins (wildtype and mutated forms) into cells such that the functional consequences of mutations on channel function, cell proliferation, and response to agonists can be asessed. These structure-function experiments permit the necessity and sufficiency of specific residues, domains, and functions of these proteins to these functions to be determined. We also use animal models to evaluate the necessity and sufficiency for specific connexins to the response of tissues to injury.