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.
Real time imaging of single extracellular vesicle pH regulation in a microfluidic cross-flow filtration platform.
Real time imaging of single extracellular vesicle pH regulation in a microfluidic cross-flow filtration platform. Commun Biol. 2022 01 10; 5(1):13.
PMID: 35013561
Phagosomal chloride dynamics in the alveolar macrophage.
Phagosomal chloride dynamics in the alveolar macrophage. iScience. 2022 Jan 21; 25(1):103636.
PMID: 35024579
Kinetic Separation of Oxidative and Non-oxidative Metabolism in Single Phagosomes from Alveolar Macrophages: Impact on Bacterial Killing.
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.
PMID: 33251491
Claudin-2-dependent paracellular channels are dynamically gated.
Claudin-2-dependent paracellular channels are dynamically gated. Elife. 2015 Nov 14; 4:e09906.
PMID: 26568313
TRPC6 channel translocation into phagosomal membrane augments phagosomal function.
TRPC6 channel translocation into phagosomal membrane augments phagosomal function. Proc Natl Acad Sci U S A. 2015 Nov 24; 112(47):E6486-95.
PMID: 26604306
HEK-293 cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR): a model for studying regulation of Cl- transport.
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).
PMID: 25263207
CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses.
CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses. J Physiol. 2013 Feb 15; 591(4):1001-15.
PMID: 23165767
Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.
Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus. Nat Neurosci. 2011 Apr; 14(4):487-94.
PMID: 21378974
Response to Jentsch et al.
Response to Jentsch et al. Cell Metab. 2010 Oct 06; 12(4):310.
PMID: 30029307
Disease-causing mutations in the cystic fibrosis transmembrane conductance regulator determine the functional responses of alveolar macrophages.
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.
PMID: 19837664