A5015909099- 3D Printing in Biomedical Research
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Peptidase Inhibition and Analysis
- Asthma and respiratory diseases
- Phagocytosis and Immune Regulation
- Protease and Inhibitor Mechanisms
- Pluripotent Stem Cells Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Angiogenesis and VEGF in Cancer
- Neuroscience and Neural Engineering
- Inhalation and Respiratory Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Erythrocyte Function and Pathophysiology
- Advanced Drug Delivery Systems
- Carcinogens and Genotoxicity Assessment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Biomarkers in Disease Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Gestational Diabetes Research and Management
University of Wisconsin–Madison
2013-2024
Highland Community College - Illinois
2017
University of Nottingham
2016
Queen's Medical Centre
2016
Aston University
2010-2014
Nottingham Biomedical Research Centre
2012
University of Birmingham
2006-2008
Cancer Research UK
2006
This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo liver tumor cell line lysate (HepG2) in patients advanced hepatocellular carcinoma (HCC). HCC an attractive target for immunotherapy as evidenced by active recruitment tumor-infiltrating lymphocytes that are capable lysing studies. DCs most potent antigen-presenting cells, capacity to take up, process, present antigens T stimulate...
The aim of the current study was to evaluate primary (human bronchial epithelial cells, HBEC) and non-primary (Calu-3, BEAS-2B, BEAS-2B R1) cell culture systems as air-liquid interface- (ALI-) differentiated models for asthma research. Ability differentiate into goblet (MUC5AC+) ciliated (β-Tubulin IV+) cells evaluated by confocal imaging qPCR. Expression tight junction/adhesion proteins (ZO-1, E-Cadherin) development transepithelial electrical resistance (TEER) were assessed. Primary showed...
The tailorable properties of synthetic polyethylene glycol (PEG) hydrogels make them an attractive substrate for human organoid assembly. Here, we formed neural organoids from iPSC-derived progenitor cells in two distinct formats: (i) seeded on a Matrigel surface; and (ii) PEG hydrogel surface. Tissue assembly resulted three dimensional (3D) planar with greater neuronal diversity, expression neurovascular neuroinflammatory genes, reduced variability when compared tissues assembled upon...
A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging have been implicated within the complex sequential processes that result in phagocytosis and degradation cells. Intercellular adhesion molecule 3 (ICAM-3, also known CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously cell clearance, although its precise role clearance process is ill defined. The main objective this work to...
Myofibroblasts have increased expression of contractile proteins and display augmented contractility. It is not known if the gene characterizing myofibroblast phenotype impacts its intrinsic ability to assemble fibronectin (FN) extracellular matrix. In this study we investigated whether myofibroblasts displayed rates FN fibril assembly when compared with their undifferentiated counterparts. Freshly plated exogenous (488-FN) into a fibrillar matrix more rapidly than fibroblasts that undergone...
Myofibroblasts, the primary effector cells that mediate matrix remodeling during pulmonary fibrosis, rapidly assemble an extracellular fibronectin matrix. Tensin (TNS) 1 is a key component of specialized cellular adhesions (fibrillar adhesions) bind to fibrils. We hypothesized TNS1 may play role in modulating myofibroblast-mediated formation. found expression increased fibroblastic foci from lungs with idiopathic fibrosis. Transforming growth factor (TGF)-β profoundly up-regulates kinetics...
The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release toxic granule proteins other mediators, including cytokines. Tissue consequent functional defects are affected by activity connective fibroblasts. Exaggerated fibroblast activation, accumulation change phenotype may lead fibrosis loss function. So far, little information has been reported on how affect via the activation We have recently shown that eosinophil IL-3 led a robust...
Macrolides including azithromycin (AZM) can improve clinical symptoms in asthma regardless of infection status. The mechanisms underlying these beneficial effects are yet to be elucidated. aim this study was determine the effect AZM on airway epithelial barrier both an vitro model and patients with asthma. Primary human bronchial cells (HBEC) were grown at air liquid interface (ALI) challenged using lipopolysaccharides from Pseudomonas aeruginosa. added various stages integrity assessed...
Abstract There is a vital need to develop in vitro models of the developing human brain recapitulate biological effects that toxic compounds have on brain. To model perineural vascular plexus (PNVP) vitro, which key stage embryonic development, stem cells (hESC)‐derived endothelial (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) synthetic hydrogels custom‐designed microfluidics device are cocultured. The formation includes networks ECs (CD31+, VE‐cadherin+),...
We used SEREX technology to identify novel tumour-associated antigens in patients with primary hepatocellular carcinoma and found serological responses the polycomb group (PcG) protein BMI-1, which is overexpressed a range of different tumour types. Further studies identified T-cell both BMI-1 another PcG protein, EZH2, cancer at relatively lower levels some normal donors. next several CD8+ epitopes derived from EZH2 demonstrated that EZH2-derived peptides elicited more significant...
Fibrosing disorders of the lung, such as idiopathic pulmonary fibrosis, are characterized by progressive extracellular matrix accumulation that is driven myofibroblasts. The transcription factor megakaryoblastic leukemia-1 (MKL1) mediates myofibroblast differentiation in response to several profibrotic stimuli, but role it plays mediating fibrosis has not been fully elucidated. In this study, we utilized mice had a germline deletion MKL1 (MKL1 (−,-)) determine development bleomycin-induced...
Vascularization is an important strategy to overcome diffusion limits and enable the formation of complex, physiologically relevant engineered tissues organoids. Self-assembly a technique generate in vitro vascular networks, but engineering necessary network morphology function remains challenging. Here, autofluorescence multiphoton microscopy (aMPM), label-free imaging technique, used quantitatively evaluate morphology. Vascular networks are generated using human embryonic stem cell-derived...
Pericytes play a critical role in promoting, regulating, and maintaining numerous vascular functions. Their dysfunction is major contributor to the progression of neurodegenerative diseases, making them an ideal candidate for large-scale production disease modeling regenerative cell therapy. This protocol describes rapid robust differentiation pericytes from human induced pluripotent stem cells (hiPSCs) while simultaneously generating population hiPSC-derived endothelial progenitor cells....
Semaphorin-7A is a glycosylphosphatidylinositol-anchored protein, initially characterized as an axon guidance protein. also contributes to immune cell regulation and may be essential pro-fibrotic factor when expressed by non-fibroblast types (exogenous). In mouse models, semaphorin-7A was shown important for TGF-ß1-induced pulmonary fibrosis myofibroblast accumulation extracellular matrix deposition, but the cell-specific role of not examined in fibroblasts. The purpose this study determine...
Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions Bipolar disorder Epilepsy. However, these have potential developmental effects that not fully understood. This study explores use of a simple human neurosphere-based in vitro model to characterise pharmacological toxicological LiCl VPA using gene expression changes linked phenotypic alterations cells. Treatment with resulted differential 331 164 genes respectively. In...
Idiopathic pulmonary fibrosis is a progressive and deadly disorder with very few therapeutic options. Palomid 529 (8-(1-hydroxyethyl)-2-methoxy-3-(4-methoxybenzyloxy)-benzo[c]chromen-6-one; P529) novel dual inhibitor of mechanistic target rapamycin complex 1/2 (mTORC1/2). In these studies, we investigated the effect P529 on TGF-β-dependent signaling myofibroblast differentiation. TGF-β-induced phosphorylation mTORC1 targets, p70 S6 kinase 1 (S6K1), eukaryotic translation initiation factor 4E...
Extracellular vesicles (EVs) play crucial roles in cell-cell communication, but the biogenesis of large EVs has remained elusive. Here, we show that (>800nm-2um) occurs predominantly through completion successful cytokinesis, and majority extracellular are midbody remnants (MBRs) with translation activity, unique marker MKLP1. Blocking cell cycle or genetically chemically, significantly decreases MBRs (800nm-2um), medium (500-800nm), small (<300nm) EVs, suggesting proliferative cells can...
The airway epithelium is altered in respiratory disease and thought to contribute etiology. A caveat research that the technique of isolation bronchial epithelial cells from patients invasive have a limited lifespan. aim this study was extensively characterize plasticity primary human been engineered delay cell senescence including ability these differentiate. Cells were express BMI-1 or hTERT using viral vector systems. characterized at passage (p) early (p5), mid (p10), late (p15) stage...
Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct protein delivery (protein transduction) provides conceptually simpler alternative, but in practice approach problematic. Domains such as HIV TAT...
Traditionally, midbody remnants (MBRs) are isolated from cell culture medium using ultracentrifugation, which is expensive and time consuming. Here, we present a protocol for isolating MBRs or large extracellular vesicles (EVs) mammalian either 1.5% polyethylene glycol 6000 (PEG6000) PEG5000-coated gold nanoparticles. We describe steps growing cells, collecting media, precipitating EVs medium. then detail characterization of through immunofluorescent antibody staining imaging.
Scanning electron microscopy (SEM) image of the vascular network represents pericytes that are wrapped around apparent endothelial cell lumen. In article 1801186, William T. Daly, L. Murphy, and co-workers, create three-dimensional networks in a synthetic PEG hydrogel under influence dynamic flow conditions. Changes morphology is visualized quantified by autofluorescence multiphoton microscopy.
Abstract Cells communicate with neighboring cells through shedding and uptake of extracellular vesicles (EVs). EVs are small packages nucleic acid protein enclosed in a lipid bilayer. Despite being broadly studied since 2010, the biogenesis remains elusive. Currently, interphase thought to shed bulk EVs. Given that cancer more than non-cancerous cells, we hypothesized primary origin large may be mitosis. Here, demonstrate occurs We found canonical EV markers, CD9, CD63, CD81, flotillin-1,...