Christopher A. Ahern
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View article: Single-cell RNA sequencing of lung leukocytes from cystic fibrosis mice after mucosal vaccination reveals differential gene expression in leukocyte subsets and links to dysregulated Th17 responses 4056
Single-cell RNA sequencing of lung leukocytes from cystic fibrosis mice after mucosal vaccination reveals differential gene expression in leukocyte subsets and links to dysregulated Th17 responses 4056 Open
Description Chronic Pseudomonas aeruginosa lung infection poses a significant threat to individuals with cystic fibrosis (CF), yet effective vaccine strategies remain elusive. Our previous work demonstrated that an intranasal (IN) vaccine …
View article: Position-dependent effects of <i>SCN2A</i> premature stop codons on neuronal excitability and behavior
Position-dependent effects of <i>SCN2A</i> premature stop codons on neuronal excitability and behavior Open
SCN2A encodes the voltage-gated sodium channel Na V 1.2, a key determinant of spike initiation and propagation in glutamatergic neurons. Premature termination codons are often assumed to produce uniform haploinsufficiency via nonsense-medi…
View article: Non-canonical Sodium Channel Isoforms Underlie Chamber Specific Cardiac Excitability
Non-canonical Sodium Channel Isoforms Underlie Chamber Specific Cardiac Excitability Open
Voltage-gated sodium (Na V ) channels drive cardiac excitability. While Na V 1.5 is the primary cardiac isoform, the composition and functional contributions of non-Na V 1.5 isoforms in the heart remain unclear. Here, we developed a chemic…
View article: De novo mutations mediate phenotypic switching in an opportunistic human lung pathogen
De novo mutations mediate phenotypic switching in an opportunistic human lung pathogen Open
Bacteria evolving within human hosts encounter selective tradeoffs that render mutations adaptive in one context and deleterious in another. Here, we report that the cystic fibrosis-associated pathogen Burkholderia dolosa overcomes in-huma…
View article: Preventing vision loss in a mouse model of Leber Congenital Amaurosis by engineered tRNA
Preventing vision loss in a mouse model of Leber Congenital Amaurosis by engineered tRNA Open
Premature termination codons (PTCs) are associated with rare genetic disorders. Inducing targeted read-through of these ‘nonsense mutations’ presents a potential therapeutic strategy for modifying disease outcomes. We previously reported t…
View article: Molecular Basis of Sodium Channel Inactivation
Molecular Basis of Sodium Channel Inactivation Open
Voltage-gated sodium channels initiate action potentials and control electrical signaling throughout the animal kingdom. Fast inactivation is an essential auto-inhibitory mechanism and requisite component of sodium channel physiology. Rece…
View article: A single main-chain hydrogen bond required to keep GABA<sub>A</sub>receptors closed
A single main-chain hydrogen bond required to keep GABA<sub>A</sub>receptors closed Open
GABA A receptors are the primary inhibitory neurotransmitter receptors throughout the central nervous system. Despite significant progress understanding their three-dimensional structure, a critical gap remains in determining the molecular…
View article: Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy
Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy Open
Peripheral Myelin Protein 22 (PMP22) and MPZ are abundant myelin membrane proteins in Schwann cells. The MPZ adhesion protein holds myelin wraps together across the intraperiod line. PMP22 is a tetraspan protein belonging to the Claudin su…
View article: Rapid discovery and evolution of nanosensors containing fluorogenic amino acids
Rapid discovery and evolution of nanosensors containing fluorogenic amino acids Open
Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on…
View article: Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology
Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology Open
Ion channels play central roles in biology and human health by catalyzing the transmembrane flow of electrical charge. These proteins are ideal targets for genetic code expansion (GCE) methods because it is feasible to measure ion channel …
View article: Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy
Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy Open
PMP22 and MPZ are abundant myelin membrane proteins in Schwann cells. The MPZ adhesion protein holds myelin wraps together across the intraperiod line. PMP22 is a tetraspan protein belonging to the Claudin superfamily. Loss of either MPZ o…
View article: Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal subunit regulation of the cardiac voltage-gated sodium channel
Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal subunit regulation of the cardiac voltage-gated sodium channel Open
Voltage-gated sodium (NaV) channels drive the upstroke of the action potential and are comprised of a pore-forming α-subunit and regulatory β-subunits. The β-subunits modulate the gating, trafficking, and pharmacology of the α-subunit. The…
View article: Homomeric interactions of the MPZ Ig domain and their relation to Charcot-Marie-Tooth disease
Homomeric interactions of the MPZ Ig domain and their relation to Charcot-Marie-Tooth disease Open
Mutations in MPZ (myelin protein zero) can cause demyelinating early-onset Charcot-Marie-Tooth type 1B disease or later onset type 2I/J disease characterized by axonal degeneration, reflecting the diverse roles of MPZ in Schwann cells. MPZ…
View article: Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal new properties of the cardiac voltage-gated sodium channel
Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal new properties of the cardiac voltage-gated sodium channel Open
Voltage-gated sodium (Na V ) channels drive the upstroke of the action potential and are comprised of a pore-forming α-subunit and regulatory β-subunits. The β-subunits modulate the gating, trafficking, and pharmacology of the α-subunit. T…
View article: Structural context of homomeric interactions in the lg domain of the MPZ (P0) myelin adhesion protein and relation to Charcot-Marie-Tooth disease phenotype variants
Structural context of homomeric interactions in the lg domain of the MPZ (P0) myelin adhesion protein and relation to Charcot-Marie-Tooth disease phenotype variants Open
Mutations in Myelin Protein Zero (MPZ) account for 5% of Charcot-Marie-Tooth cases and can cause demyelinating or axonal phenotypes, reflecting the diverse roles of MPZ in Schwann cells. MPZ holds the apposing membranes of the myelin sheat…
View article: Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel
Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel Open
Voltage-gated ion channels (VGICs) orchestrate electrical activities that drive mechanical functions in contractile tissues such as the heart and gut. In turn, contractions change membrane tension and impact ion channels. VGICs are mechano…
View article: Phospholipase C‐ε defines a <scp>PACAP</scp>‐stimulated pathway for secretion in the chromaffin cell
Phospholipase C‐ε defines a <span>PACAP</span>‐stimulated pathway for secretion in the chromaffin cell Open
Adrenomedullary chromaffin cells respond to splanchnic (sympathetic) nerve stimulation by releasing stress hormones into the circulation. The signal for hormone secretion is encoded in the neurotransmitters – especially acetylcholine (ACh)…
View article: Real-time observation of functional specialization among phosphorylation sites in CFTR
Real-time observation of functional specialization among phosphorylation sites in CFTR Open
Phosphoregulation is ubiquitous in biology. Defining the functional roles of individual phosphorylation sites within a multivalent system remains particularly challenging. We have therefore applied a chemical biology approach to light-cont…
View article: Chemically Acylated tRNAs are Functional in Zebrafish Embryos
Chemically Acylated tRNAs are Functional in Zebrafish Embryos Open
Genetic code expansion has pushed protein chemistry past the canonical 22 amino acids. The key enzymes that make this possible are engineered aminoacyl tRNA synthetases. However, as the number of genetically encoded amino acids has increas…
View article: Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells
Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells Open
The aromatic side-chains of phenylalanine, tyrosine, and tryptophan interact with their environments via both hydrophobic and electrostatic interactions. Determining the extent to which these contribute to protein function and stability is…
View article: Backbone amides are determinants of Cl− selectivity in CLC ion channels
Backbone amides are determinants of Cl− selectivity in CLC ion channels Open
Chloride homeostasis is regulated in all cellular compartments. CLC-type channels selectively transport Cl − across biological membranes. It is proposed that side-chains of pore-lining residues determine Cl − selectivity in CLC-type channe…
View article: Backbone amides are determinants of Cl− selectivity in CLC ion channels
Backbone amides are determinants of Cl− selectivity in CLC ion channels Open
MD-related files, including all the trajectories, analysis scripts, and NAMD input files. There are two folders: 1- trajectories: trajectory files (dcd) for both mutant and wild type systems (cl, br, no3, and I ions) 2- scripts-parameters:…
View article: Tuning aromatic contributions by site-specific encoding of fluorinated phenylalanine residues in bacterial and mammalian cells
Tuning aromatic contributions by site-specific encoding of fluorinated phenylalanine residues in bacterial and mammalian cells Open
The aromatic side-chains of phenylalanine, tyrosine, and tryptophan interact with their environments via both hydrophobic and electrostatic interactions. Determining the extent to which these contribute to protein function and stability is…