Research Summary
The Nelson lab is interested in the role of ion channels in disease processes. Most recently, this has lead us to the study of the involvement of anion channels in innate immune processes, in neural secretion, in bone formation and in pancreatic hormone processing. Characterization of channel function has utilized a spectrum of tools including super-resolution microscopy, microfluidics, optogenetics, patch clamp electrophysiology, live cell fluorescence microscopy and basic biochemical techniques. We have created mouse models of channel mutations using CRISPER-Cas gene editing to examine loss of channel function in a variety of organ contexts. Anion channels drive a diversity of intracellular function and vesicle content at the molecular level and neuronal inhibition and microbicidal function at the cellular level. At the organellar level, they build new bone and process hormones for release. Anion channel loss of function results in fatal pulmonary infections in Cystic Fibrosis, osteoporosis in bone and contributes to the complex disease of diabetes. Recently, we have used microfluidic devices to visualize and quantify release of extracellular vesicles from cells in the immune system. These devices will allow us to examine fusion of individual vesicles or nanoparticles with target cells as they deliver diverse cargo including nucleic acids coding for signaling proteins and ion channels to restore function to cells lacking their expression. The extracellular vesicles are released by all cells and can be engineered to carry small therapeutic molecules and contribute to restoration of cell function. The microfluidic platform will allow us to visualize function in 3 dimensional arrays using organoids exposed to engineered extracellular vesicles. In summary, the laboratory seeks to examine cellular processes from the nanoparticle to the organellar level visualizing function from molecule to mouse model.
ion channels and disease, Electrophysiology, extracellular vesicles, live cell imaging, Microfluidic Devices, Secretion Processes, Cystic Fibrosis, Pulmonary, super resolution microscopy, optogenetics, Patch-Clamp Technique, Cell Culture Technique, Innate Immune Response, Macrophages, Nanoparticles
Biosciences Graduate Program Association
  1. Riazanski V, Sui Z, Nelson DJ. Kinetic Separation of Oxidative and Non-oxidative Metabolism in Single Phagosomes from Alveolar Macrophages: Impact on Bacterial Killing. iScience. 2020 Nov 20; 23(11):101759. View in: PubMed

  2. Deriy LV, Gomez EA, Le BN, Philipson LH, Nelson DJ. Response to Jentsch et al. Cell Metab. 2010 Oct 06; 12(4):310. View in: PubMed

  3. Riazanski V, Gabdoulkhakova AG, Boynton LS, Eguchi RR, Deriy LV, Hogarth DK, Loaëc N, Oumata N, Galons H, Brown ME, Shevchenko P, Gallan AJ, Yoo SG, Naren AP, Villereal ML, Beacham DW, Bindokas VP, Birnbaumer L, Meijer L, Nelson DJ. TRPC6 channel translocation into phagosomal membrane augments phagosomal function. Proc Natl Acad Sci U S A. 2015 Nov 24; 112(47):E6486-95. View in: PubMed

  4. Weber CR, Liang GH, Wang Y, Das S, Shen L, Yu AS, Nelson DJ, Turner JR. Claudin-2-dependent paracellular channels are dynamically gated. Elife. 2015 Nov 14; 4:e09906. View in: PubMed

  5. Domingue JC, Ao M, Sarathy J, George A, Alrefai WA, Nelson DJ, Rao MC. HEK-293 cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR): a model for studying regulation of Cl- transport. Physiol Rep. 2014 Sep 01; 2(9). View in: PubMed

  6. Farmer LM, Le BN, Nelson DJ. CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses. J Physiol. 2013 Feb 15; 591(4):1001-15. View in: PubMed

  7. Riazanski V, Deriy LV, Shevchenko PD, Le B, Gomez EA, Nelson DJ. Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus. Nat Neurosci. 2011 Apr; 14(4):487-94. View in: PubMed

  8. Deriy LV, Gomez EA, Zhang G, Beacham DW, Hopson JA, Gallan AJ, Shevchenko PD, Bindokas VP, Nelson DJ. Disease-causing mutations in the cystic fibrosis transmembrane conductance regulator determine the functional responses of alveolar macrophages. J Biol Chem. 2009 Dec 18; 284(51):35926-38. View in: PubMed

  9. Deriy LV, Gomez EA, Jacobson DA, Wang X, Hopson JA, Liu XY, Zhang G, Bindokas VP, Philipson LH, Nelson DJ. The granular chloride channel ClC-3 is permissive for insulin secretion. Cell Metab. 2009 Oct; 10(4):316-23. View in: PubMed

  10. Cassilly DW, Wang YR, Friedenberg FK, Nelson DB, Maurer AH, Parkman HP. Symptoms of gastroparesis: use of the gastroparesis cardinal symptom index in symptomatic patients referred for gastric emptying scintigraphy. Digestion. 2008; 78(2-3):144-51. View in: PubMed

  11. Claud EC, Lu J, Wang XQ, Abe M, Petrof EO, Sun J, Nelson DJ, Marks J, Jilling T. Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008 May; 294(5):G1191-200. View in: PubMed

  12. Wang XQ, Deriy LV, Foss S, Huang P, Lamb FS, Kaetzel MA, Bindokas V, Marks JD, Nelson DJ. CLC-3 channels modulate excitatory synaptic transmission in hippocampal neurons. Neuron. 2006 Oct 19; 52(2):321-33. View in: PubMed

  13. Di A, Brown ME, Deriy LV, Li C, Szeto FL, Chen Y, Huang P, Tong J, Naren AP, Bindokas V, Palfrey HC, Nelson DJ. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol. 2006 Sep; 8(9):933-44. View in: PubMed

  14. Wang CZ, Wang Y, Di A, Magnuson MA, Ye H, Roe MW, Nelson DJ, Bell GI, Philipson LH. 5-amino-imidazole carboxamide riboside acutely potentiates glucose-stimulated insulin secretion from mouse pancreatic islets by KATP channel-dependent and -independent pathways. Biochem Biophys Res Commun. 2005 May 20; 330(4):1073-9. View in: PubMed

  15. Sarac R, Hou P, Hurley KM, Hriciste D, Cohen NA, Nelson DJ. Mutation of critical GIRK subunit residues disrupts N- and C-termini association and channel function. J Neurosci. 2005 Feb 16; 25(7):1836-46. View in: PubMed

  16. Di A, Nelson DJ, Bindokas V, Brown ME, Libunao F, Palfrey HC. Dynamin regulates focal exocytosis in phagocytosing macrophages. Mol Biol Cell. 2003 May; 14(5):2016-28. View in: PubMed

  17. Di A, Krupa B, Bindokas VP, Chen Y, Brown ME, Palfrey HC, Naren AP, Kirk KL, Nelson DJ. Quantal release of free radicals during exocytosis of phagosomes. Nat Cell Biol. 2002 Apr; 4(4):279-85. View in: PubMed

  18. Chang SY, Di A, Naren AP, Palfrey HC, Kirk KL, Nelson DJ. Mechanisms of CFTR regulation by syntaxin 1A and PKA. J Cell Sci. 2002 Feb 15; 115(Pt 4):783-91. View in: PubMed