The Lampe laboratory investigates the control of cell growth both at the cell biological/ mechanistic level and through cancer biomarker discovery. We study the cell biology connecting gap junctions and intercellular communication (GJIC) with the control of cell growth, the cell cycle and, how the relationship is disrupted during carcinogenesis.
Our interest in gap junctions as potential biomarkers of cancer and, more recently, the advent of new screening methodologies has expanded our efforts into broad proteomic screens for potential cancer biomarkers using mass spectrometry (MS) and recombinant antibody array technologies. We are currently collaborating with several Seattle and National and International colleagues to study potential biomarkers for ovarian, colon and breast cancer.
Our ongoing cell/molecular research involves the regulation of gap junction assembly and function. Gap junctions allow diffusion of small molecules (<1000 MW) between adjacent cells via matched cell-to-cell membrane channels. Cell-cell communication via these channels is known to play an important role in the control of cell proliferation, embryonic development, cell differentiation, and the regulation of differentiated function in post-mitotic cells. Vertebrate gap junctions are composed of proteins derived from the connexin gene family, and our results indicate that gap junction formation and degradation are highly regulated via protein kinases at various stages of the assembly process and the cell cycle.
Ongoing studies include determination of the cellular localization of different connexin phosphorylation events and the specific serine substrates that are phosphorylated within connexins at different stages of the cell cycle. Thus, we attempt to link the activation of specific kinases to phosphorylation on a particular residue within the connexin protein and to connexin function in tissue including skin and heart. Our data indicates that kinases such as PKA, PKC, CK1, cdc2/cyclinB, MAP-K and others regulate specific steps of gap junction protein export, assembly, channel gating and degradation in a cell cycle dependent manner. The connection between cell cycle control and gap junctions has recently been strengthened by our data linking the cell cycle regulatory protein p27 with connexin expression. To perform these studies of gap junction function, we utilize a variety of cell, molecular and biochemical techniques including GFP chimeras to monitor gap junctions in living cells.