A5050166967- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Inhalation and Respiratory Drug Delivery
- Heavy Metal Exposure and Toxicity
- Pediatric health and respiratory diseases
- Ion Transport and Channel Regulation
- Immune Response and Inflammation
- Autophagy in Disease and Therapy
- Ion channel regulation and function
- Cellular transport and secretion
- Inflammasome and immune disorders
- Gut microbiota and health
- MicroRNA in disease regulation
- Air Quality and Health Impacts
- Smoking Behavior and Cessation
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- Bacterial biofilms and quorum sensing
- Bacillus and Francisella bacterial research
- Respiratory viral infections research
- CRISPR and Genetic Engineering
- Bacterial Infections and Vaccines
The Ohio State University
2016-2025
University of Iowa
2023
Ohio University
2015-2018
Lung Institute
2008-2018
University of Alabama at Birmingham
2000-2011
The Ohio State University Wexner Medical Center
2011
Ames National Laboratory
2006
University of Tennessee Health Science Center
2004
University of Chicago
2002
University of Alabama
2002
Abstract Robust in vitro lung models are required for risk assessment to measure key events leading respiratory diseases. Primary normal human bronchial epithelial cells (NHBE) represent a good model but obtaining well-differentiated 3D cultures can be challenging. Here, we evaluated the ability expand primary NHBE different culture conditions while maintaining their characteristics such as ciliated and goblet cells, ion channel function. Differentiated were optimally obtained with...
The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Fibrosis, disease characterized chronic infection and inflammation. We recently reported air pollutants such as cigarette smoke cadmium negatively regulate expression affecting several steps biogenesis protein. MicroRNAs (miRNAs) have received great deal attention both biomarkers therapeutics due...
The tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus responsible for the ongoing disease 2019 (COVID-19) pandemic, toward host cells is determined, at least in part, by expression and distribution its cell surface receptor, angiotensin-converting enzyme (ACE2). further exploits cellular machinery to gain access into cells; spike protein cleaved transmembrane serine protease (TMPRSS2) shortly after binding ACE2, followed proteolytic activation furin cleavage...
Significance We report the discovery of fundamental roles for noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role immune responses beyond its previously appreciated effects bacterial Further, we show Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better terms overall illness, lung...
The cystic fibrosis gene encodes a chloride channel, CFTR (cystic transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates an unknown mechanism. amino-terminal tail was found to control A–dependent channel gating through physical interaction with R domain. This activity mapped cluster acidic residues in NH 2 -terminal tail; mutating these proportionately...
Proteasome inhibition represents a promising strategy of cancer pharmacotherapy, but resistant tumor cells often emerge. Here we show that the microRNA-101 (miR-101) targets proteasome maturation protein POMP, leading to impaired assembly and activity, resulting in accumulation p53 cyclin-dependent kinase inhibitors, cell cycle arrest, apoptosis. miR-101-resistant POMP restores proper turnover substrates re-enables growth. In ERα-positive breast cancers, miR-101 levels are inversely...
Abstract A general strategy was developed for the intracellular delivery of linear peptidyl ligands through fusion to a cell‐penetrating peptide and cyclization peptides via disulfide bond. The resulting cyclic are cell permeable have improved proteolytic stability. Once inside cell, bond is reduced produce biologically active peptides. This applied generate cell‐permeable substrate real‐time detection caspase activities during apoptosis an inhibitor CFTR‐associated ligand (CAL) PDZ domain...
Cystic fibrosis (CF) is a fatal, genetic disorder that critically affects the lungs and directly caused by mutations in CF transmembrane conductance regulator (CFTR) gene, resulting defective CFTR function. Macroautophagy/autophagy highly regulated biological process provides energy during periods of stress starvation. Autophagy clears pathogens dysfunctional protein aggregates within macrophages. However, this impaired patients mice, as their macrophages exhibit limited autophagy activity....
Autophagy is a proposed route of amyloid-β (Aβ) clearance by microglia that halted in Alzheimer's Disease (AD), though mechanisms underlying this dysfunction remain elusive. Here, primary from adult AD (5xFAD) mice were utilized to demonstrate 5xFAD fail degrade Aβ and express low levels autophagy cargo receptor NBR1. In mouse brains, we show for the first time elevated microRNA cluster Mirc1/Mir17-92a, which known downregulate proteins. By situ hybridization post-mortem human tissue...
5-methylcytosine (m 5 C) is one of the most prevalent modifications RNA, playing important roles in RNA metabolism, nuclear export, and translation. However, potential role m C methylation innate immunity remains elusive. Here, we show that depletion NSUN2, an methyltransferase, significantly inhibits replication gene expression a wide range DNA viruses. Notably, found this antiviral effect largely driven by enhanced type I interferon (IFN) response. The signaling pathway dependent on...
The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells. Decreased CFTR expression and/or function lead to impaired surface liquid (ASL) volume homeostasis, resulting accumulation of mucus, reduced clearance bacteria, and chronic infection inflammation. Expression the cigarette smoke metal content were assessed lung samples controls COPD patients with established GOLD stage 4. protein mRNA quantified by...
Cadmium (Cd), a toxic heavy metal and carcinogen that is abundantly present in cigarette smoke, cause of smoking-induced lung disease. SLC39A8 (ZIP8), zinc transporter, major portal for Cd uptake into cells. We have recently identified ZIP8 expression under the transcriptional control NF-κB pathway. On basis this, we hypothesized cigarette-smoke induced inflammation would increase epithelia, thereby enhancing cell toxicity. Herein report central mediator Cd-mediated TNF-α treatment primary...
Background: Secondhand smoke exposure (SHSe) is a public health threat for people with cystic fibrosis (CF) and other lung diseases. Primary smoking reduces CFTR channel function, the causative defect in CF. We reported that SHSe worsens respiratory nutritional outcomes CF by disrupting immune responses metabolic signaling. Recently, electronic cigarette (e-cigs) usage caregivers peers has increased rapidly, causing new secondhand e-cig vape exposures. vaping associated immunologic deficits...
Soluble N- ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate membrane fusion reactions in eukaryotic cells by assembling into complexes that link vesicle-associated SNAREs with on target membranes (t-SNAREs). Many SNARE contain two t-SNAREs form a heterodimer, putative intermediate assembly. Individual (e.g., syntaxin 1A) also regulate synaptic calcium channels and cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial chloride channel is...
Cadmium is a toxic heavy metal ranked seventh on the Priority List of Hazardous Substances. As byproduct smelters, cadmium prevalent environmental contaminant. It also major component cigarette smoke, and its inhalation associated with decreased pulmonary function, lung cancer, chronic obstructive disease. Ion channels, including cystic fibrosis transmembrane conductance regulator (CFTR), play central role in maintaining fluid homeostasis functions. CFTR mostly expressed epithelial cells,...
We have utilized small interfering RNA (siRNA)-mediated depletion of the β-COP subunit COP-I to explore function in organellar compartmentalization and protein traffic. Reduction levels causes colocalization markers for endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN), recycling endosomes large, globular compartments. The lack spatial differentiation these compartments is not due a general collapse all cellular organelles since early...
Airway epithelial cells in the lung are first line of defense against pathogens and environmental pollutants. Inhalation pollutant cadmium has been linked to development cancer chronic obstructive pulmonary disease, which diseases characterized by inflammation. To address role airway cadmium-induced inflammation, we investigated how regulates secretion interleukin 8 (IL-8) cells. We show that exposure human subtoxic doses vitro promotes a characteristic inflammatory cytokine response...
The CFTR Cl– channel controls salt and water transport across epithelial tissues. Previously, we showed that CFTR-mediated currents in the Xenopus oocyte expression system are inhibited by syntaxin 1A, a component of membrane trafficking machinery. This negative modulation function can be reversed soluble 1A peptides binding protein, Munc-18. In present study, determined whether is expressed native tissues normally express it modulates these Using immunoblotting immunofluorescence, observed...
Most cases of cystic fibrosis (CF) are caused by mutations that block the biosynthetic maturation CF gene product, transmembrane conductance regulator (CFTR) chloride channel. CFTR-processing mutants fail to escape endoplasmic reticulum and rapidly degraded. Current efforts induce CFTR target components pathway (e.g., chaperones) rather than per se . Such methods inherently nonspecific. Here we show most common CF-causing mutant (ΔF508-CFTR) can form mature, functional channels reach cell...
Particulate matter (PM) exposure induces a pathological response from both the lungs and cardiovascular system. PM is capable of manifestation into lung epithelium entrance bloodstream. Therefore, has capacity for direct lung-mediated indirect effects on heart. In present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate (diesel exhaust particles, DEP) examined their contractile function calcium handling ability. another set experiments, epithelial cells (16HBE14o- or...
Significance We report that suppression of the serine protease elastase reshapes innate responses induced by injected vaccines containing alum adjuvant. This reprogramming improves induction protective antibodies in bloodstream and stimulates signals, which support development antibody mucosal tissues. Our findings identify as regulator blunts adjuvant activity alum. They also demonstrate vaccination via routes is not an absolute requirement for tissues secretions. Supplementation alum-based...