Paul D. Lampe
Ph.D., University of Minnesota, Biochemistry, 1984.
BA, Carleton College, 1979.
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, pancreas, 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.
Current Laboratory Members:
Joell Solan - Postdoc
Lucrecia Marquez-Rosado - Postdoc
Clarence Dunn - Postdoc
Rachael Norris - Postdoc
Jung Hyun Rho - Postdoc
Steven Chen - Grad Student, Biochemistry program
Justin Mirus - Grad Student, MCB program
Perry Thornton - Technician
Injury-triggered Akt phosphorylation of Cx43: a ZO-1-driven molecular switch that regulates gap junction size.. Journal of cell science. 127(Pt 2):455-64.. 2014.
High-throughput screening for native autoantigen-autoantibody complexes using antibody microarrays.. Journal of proteome research. 12(5):2311-20.. 2013.
Cardiomyocyte FGF signaling is required for Cx43 phosphorylation and cardiac gap junction maintenance.. Experimental cell research.. 2013.
Connexins and steroidogenesis in mouse Leydig cells.. Canadian journal of physiology and pharmacology. 91(2):157-64.. 2013.
Histone deacetylase inhibition reduces cardiac connexin43 expression and gap junction communication.. Frontiers in pharmacology. 4:44.. 2013.
Loss of MAPK Phosphorylation of Connexin43 is Neuroprotective in Stroke. Stroke. 44:E211–E211.. 2013.
Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women's Health Initiative observational study.. Breast cancer research and treatment. 135(2):611-8.. 2012.
Introduction paper of the special issue on gap junctions in honor of ross johnson.. The Journal of membrane biology. 245(5-6):217-9.. 2012.
Phosphorylation of Serine Residues in the C-terminal Cytoplasmic Tail of Connexin43 Regulates Proliferation of Ovarian Granulosa Cells.. The Journal of membrane biology. 245(5-6):291-301.. 2012.
MAPK phosphorylation of connexin 43 promotes binding of cyclin e and smooth muscle cell proliferation.. Circulation research. 111(2):201-11.. 2012.
Activation of AKT, but not connexin43 ubiquitination, regulates gap junction stability.. The Journal of biological chemistry. 287(4):2600-7.. 2012.
CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects cell migration.. Journal of cell science. 125(Pt 3):695-702.. 2012.
Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects.. Experimental cell research.. 2012.
Connexin43 phosphorylation in brain, cardiac, endothelial and epithelial tissues.. Biochimica et biophysica acta. 1818(8):1985-92.. 2012.
Increased plasma levels of the APC-interacting protein MAPRE1, LRG1 and IGFBP2 preceding a diagnosis of colorectal cancer in women.. Cancer prevention research (Philadelphia, Pa.). 5(4):655-664.. 2012.
Evaluating the role of connexin43 in congenital heart disease: Screening for mutations in patients with outflow tract anomalies and the analysis of knock-in mouse models.. Journal of cardiovascular disease research. 2(4):206-12.. 2011.
Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.. Cancer research. 70(21):8598-606.. 2010.
Trafficking and recycling of the connexin43 gap junction protein during mitosis.. Traffic (Copenhagen, Denmark). 11(11):1471-86.. 2010.
Use of a single-chain antibody library for ovarian cancer biomarker discovery.. Molecular & cellular proteomics : MCP. 9(7):1449-60.. 2010.
Consortin, a trans-Golgi network cargo receptor for the plasma membrane targeting and recycling of connexins.. Human molecular genetics. 19(2):262-75.. 2010.