Janis M Burt, PhD

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.