Biology subjects

Luke, C.

Publications and source records attributed to Luke, C..

5 recordsLinked to original sources

bioRxiv2025

Stathmin 1 regulates mitophagy and cellular function in hematopoietic stem cells

Stathmin 1 is a cytoplasmic phosphoprotein that regulates microtubule dynamics via promotion of microtubule catastrophe and sequestration of free tubulin heterodimers. Stathmin 1 is highly expressed in hematopoietic stem cells (HSCs), and overexpressed in leukemic cells, however its role in HSCs is not known. Herein, we found that loss of Stathmin 1 is associated with altered microtubule architecture in HSCs, and markedly impaired HSC function. Transcriptomic studies suggested alterations in oxidative phosphorylation in Stmn1-/- HSCs, and further mechanistic studies revealed defective mitochondrial structure and function in the absence of Stathmin 1 with increased ROS production. Microtubules associate with mitochondria and lysosomes to facilitate autophagosome formation and mitophagy, and indeed we found that this critical mitochondrial quality control process is impaired in Stathmin 1-deficient HSCs. Finally, stimulation of autophagy improved the colony forming ability of Stmn1-/- hematopoietic stem and progenitor cells. Together, our data identify Stathmin 1 as a novel regulator of mitophagy and mitochondrial health in HSCs. Key PointsO_LIThe microtubule regulating protein Stathmin 1 is highly expressed in HSPCs and promotes normal microtubule architecture. C_LIO_LILoss of Stathmin 1 in HSPCs leads to impaired autophagy with abnormal mitochondrial morphology, decreased respiratory capacity, and impaired cellular function. C_LI

cell biology↗

bioRxiv2023

SCCA1/SERPINB3 promotes suppressive immune environment via STAT-dependent chemokine production, blunting the therapy-induced T cell responses

Radiotherapy is a commonly used cancer treatment; however, patients with high serum squamous cell carcinoma antigen (SCCA1/SERPINB3) are associated with resistance and poor prognosis. Despite being a strong clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We investigated the microenvironment of SERPINB3 high tumors through RNAseq of primary cervix tumors and found that SERPINB3 was positively correlated with CXCL1/8, S100A8/A9 and myeloid cell infiltration. Induction of SERPINB3 in vitro resulted in increased CXCL1/8 and S100A8/A9 production, and supernatants from SERPINB3-expressing cultures attracted monocytes and MDSCs. In murine tumors, the orthologue mSerpinB3a promoted MDSC, TAM, and M2 macrophage infiltration contributing to an immunosuppressive phenotype, which was further augmented upon radiation. Radiation-enhanced T cell response was muted in SERPINB3 tumors, whereas Treg expansion was observed. A STAT-dependent mechanism was implicated, whereby inhibiting STAT signaling with ruxolitinib abrogated suppressive chemokine production. Patients with elevated pre-treatment serum SCCA and high pSTAT3 had increased intratumoral CD11b+ myeloid cell compared to patients with low SCCA and pSTAT3 cohort that had overall improved cancer specific survival after radiotherapy. These findings provide a preclinical rationale for targeting STAT signaling in tumors with high SERPINB3 to counteract the immunosuppressive microenvironment and improve response to radiation.

cancer biology↗

bioRxiv2019

Comparison of the bacterial and methanotrophic diversities between an Italian paddy field and its neighboring meadow

Methane is a potent greenhouse gas that contributes to global warming. However, under certain conditions, its release into the atmosphere can be mitigated by methane-oxidizing microorganisms. Typically, cultivated wetlands (i.e., paddy fields) are a major source of methane (CH4) while forests and meadow uplands are considered to be CH4 sinks. As the global need for rice production increases each year, more uplands are converted to inundated paddy fields. To investigate soils that may be converted into productive land for rice production, we investigated a paddy field and adjacent meadow in Northern Italy. Using a combination of 16S rRNA gene amplicon sequencing to analyze the bacterial community, and gas flux measurements to quantify CH4 emissions, we looked for differences between classically defined CH4 sinks (meadow soils) and CH4 sources (paddy fields). Analysis of the total bacterial community revealed that the family Fimbriimonadaceae, which belongs to the phylum Armatimonadetes, was significantly higher in paddy field soils driving the difference between paddy and meadow soils. Whereas, we found that the methylotrophic families Methyloligellaceae and Methylomirabilaceae were also present in higher relative abundance in the paddy field. Despite these major differences, CH4 fluxes were highly variable between the two sites with no significant differences observed. Furthermore, we found the Methylomonaceae family to be more abundant at the center of a neighboring paddy field compared to the edge of the paddy field from the current study, hinting at methanotrophic variation based on location. Taking these results into account, we propose a conceptual model to explain possible scenarios that may result in paddy and meadow fields not exhibiting classical source/sink properties. These findings call for caution when including paddy and meadow areas separately into global CH4 flux calculations, and urge further research to discern drivers of CH4 cycling under a range of environmental conditions rather than relying on assumptions.

microbiology↗

bioRxiv2018

Decrease in Microbial Diversity Along a Pollution Gradient in Citarum River Sediment

Pollution of water resources is a major risk to human health and water quality throughout the world. Here, we studied the effect of river pollution on the microbial community composition in the Citarum River Basin, West Java, Indonesia. Sediment was collected at six sampling points along a gradient of pollution, from the pristine source of the river to the heavily polluted downstream site in the densely populated urban area of Bandung. After DNA extraction, microbial diversity and potential for nitrogen cycling were analyzed based on 16S rRNA gene amplicon sequencing and metagenomics. Comparing the pristine sediment to the polluted site showed a lower microbial diversity and higher dominance of anaerobic processes than at the polluted site. The most dominant phylum within the Bacteria were the Proteobacteria, which shifted from Beta- and Deltaproteobacteria in the pristine site to Alpha- and Gammaproteobacteria in the polluted sediment. With pollution Actinobacteria, Bacteroidetes, and Firmicutes increased in relative abundance. Relative high abundance of Soil Crenarchaeotic group was found in all sample sites, whilst the methanogenic archaea became more abundant with increased pollution and anaerobicity. The study of the nitrogen cycling potential revealed that ammonium oxidation and denitrification appeared to be abundant processes in the pristine site, whereas ammonification seemed to be more important in the polluted site. Increased water treatment would restore water quality and microbial diversity in Citarum river sediments.

microbiology↗

bioRxiv2017

Linking nitrogen load to the structure and function of wetland soil and rhizosphere microbial communities

Wetland ecosystems are important reservoirs of biodiversity and significantly contribute to emissions of the greenhouse gases CO2, NO2 and CH4. High anthropogenic nitrogen (N) inputs from agriculture and fossil fuel combustion have been recognized as a severe threat to biodiversity and ecosystem functioning such as control of greenhouse gas emissions. Therefore it is important to understand how increased N input into pristine wetlands affects the composition and activity of micro-organisms, especially in interaction with dominant wetland plants. In a series of incubations analyzed over 90 days, we disentangle the effects of N fertilization on the microbial community in bulk soil and the rhizosphere of Juncus acutiflorus, a common and abundant graminoid wetland plant. We observed an increase in greenhouse gas emissions when N is increased in incubations with J. acutiflorus, changing the system from a greenhouse gas sink to a source. Using 16S rRNA amplicon sequencing and metagenomics, we determined that the bacterial orders Opitutales, Subgroup-6 Acidobacteria and Sphingobacteriales significantly responded to high N availability and we hypothesize that these groups are contributing to the increased greenhouse gas emissions. These results indicated that increased N input leads to shifts in microbial activity within the rhizosphere, severely altering N cycling dynamics. Our study provides a framework for connecting environmental conditions of wetland bulk and rhizosphere soil to the structure and metabolic output of microbial communities.

microbiology↗