Biology subjects

Hicks, R.

Publications and source records attributed to Hicks, R..

4 recordsLinked to original sources

bioRxiv2025

A highly efficient method to differentiate CGRP-expressing peptidergic nociceptors from human induced pluripotent stem cells

Human cellular models of disease developed using induced pluripotent stem cells (iPSC) have enabled wide-ranging research from investigation of human disease mechanisms to phenotypic drug screens. Pain disorders such as neuropathic pain and headache remain areas of considerable unmet need and are considered high risk by pharma. Human iPSC-derived sensory neurons have already been used to accelerate translational research but the current differentiation protocols produce non-peptidergic nociceptors. We demonstrate for the first time the robust differentiation of hiPSC into peptidergic nociceptor lineage with high yield. These nociceptors express CGRP and TRPV1 whilst the non-peptidergic marker RET was completely absent. Functionally, the nociceptors show functional maturity including the expression of TTX-resistant currents and responding to TRPV1 and TRPA1 agonists. Importantly, they were able to release CGRP basally and upon stimulation by an inflammatory soup, which was inhibited upon the application of the 5-HT1B/1D/1F agonist, sumatriptan and topiramate, a migraine prophylactic drug. Overall, we report the successful generation of a novel in vitro functional peptidergic nociceptor model which will allow investigation of disease mechanisms in pain and for the development of new effective pain therapies.

neuroscience↗

bioRxiv2025

A human induced pluripotent stem cell toolbox for studying sex chromosome effects

Sex chromosomes shape male (XY) - female (XX) differences in development and disease. These differences can be modelled in vitro by comparing XY and XX human induced pluripotent stem cells (hiPSCs). However, in this system, inter-individual autosomal variation and unstable X-dosage compensation can confound identification of sex chromosomal effects. Here, we utilise sex chromosome loss in XXY fibroblasts to generate XX and XY hiPSCs that are autosomally isogenic and exhibit stable X-dosage compensation. We also create X-monosomic (XO) hiPSCs, to investigate X-Y dosage effects. Using these autosomally isogenic lines, we examine sex differences in pluripotent stem cell expression. Transcriptional differences between XX and XY hiPSCs are surprisingly modest. However, X-haploinsufficiency induces transcriptional deregulation predominantly affecting autosomes. This effect is mediated by Y-genes with broad housekeeping functions that have X-homologues escaping X-inactivation. Our isogenic hiPSC lines provide a resource for exploring sex chromosome effects on development and disease in vitro.

genetics↗

bioRxiv2022

Field testing of an enzymatic quorum quencher coating additive to reduce biocorrosion of steel

Microbial colonization can be detrimental to the integrity of metal surfaces and lead to microbiologically influenced corrosion (MIC). Biocorrosion is a serious problem for aquatic and marine industries in the world and severely affects the maritime transportation industry by destroying port infrastructure and increasing fuel usage and the time and cost required for maintenance of transport vessels. Here, we evaluate the potential of a stable quorum quenching lactonase enzyme to reduce biocorrosion in the field. Over the course of 21 months, steel samples coated with lactonase-containing acrylic paint were submerged at two different sites and depths in the Duluth Superior Harbor (DSH; Lake Superior, MN, USA) and benchmarked against controls, including the biological biocide surfactin. In this experiment, the lactonase treatment outperformed the surfactin biocide treatment and significantly reduced the number of corrosion tubercles (37% (p<0.01)) and the corroded surface area (39% (p<0.01)) as compared to the acrylic-coated control coupons. In an attempt to evaluate the effects of signal disruption of surface microbial communities and the reasons for lower corrosion levels, 16S rRNA sequencing was performed and community populations were analyzed. Interestingly, surface communities were similar between all treatments, and only minor changes could be observed. Among these changes, several groups including sulfate-reducing bacteria (SRBs) appeared to correlate with corrosion levels, and more specifically, SRBs abundance levels were lower on lactonase treated steel coupons. We surmise that these minute community changes may have large impacts on corrosion rates. Overall, these results highlight the potential use of stable quorum quenching lactonases as an eco-friendly antifouling coating additive.

microbiology↗

bioRxiv2022

Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in In Vitro, In Vivo and Ex Vivo Models of Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two FDA approved anti-fibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications. Based on these observations, we hypothesized that saracatinib would be effective at attenuating pulmonary fibrosis. We investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: (i) in vitro in normal human lung fibroblasts (NHLFs); (ii) in vivo in bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-{beta}) murine models of pulmonary fibrosis; and (iii) ex vivo in precision cut lung slices from these mouse models. In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone.

systems biology↗