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
Kinase programs spatiotemporally regulate gap junction assembly and disassembly: effects on wound repair.. Seminars in cell & developmental biology. 50:40-48.. 2016.
Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study.. Breast cancer research and treatment. 153(2):445-54.. 2015.
Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2 Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to Continuous Flow Shear Stress.. The Journal of biological chemistry. 290(47):28321-28328.. 2015.
Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection.. Pharmacology & therapeutics.. 2015.
Role of Akt and Ca(2+) on cell permeabilization via connexin43 hemichannels induced by metabolic inhibition.. Biochimica et biophysica acta. 1852(7):1268-77.. 2015.
Acetylation mediates Cx43 reduction caused by electrical stimulation.. Journal of molecular and cellular cardiology. 87:54-64.. 2015.
Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.. Proceedings of the National Academy of Sciences of the United States of America. 112(17):5527-32.. 2015.
Cross-species antibody microarray interrogation identifies a 3-protein panel of plasma biomarkers for early diagnosis of pancreas cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research. 21(7):1764-71.. 2015.
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.
Dermcidin expression is associated with disease progression and survival among breast cancer patients.. Breast cancer research and treatment. 144(2):299-306.. 2014.
Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.. Molecular & cellular proteomics : MCP. 13(12):3484-96.. 2014.
Gap junction regulation of vascular tone: implications of modulatory intercellular communication during gestation.. Advances in experimental medicine and biology. 814:117-32.. 2014.
Specific Cx43 phosphorylation events regulate gap junction turnover in vivo.. FEBS letters. 588(8):1423-9.. 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.
Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects.. Experimental cell research. 319(6):888-96.. 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.