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overview 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.

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