Biology subjects

Sorensen, J.

Publications and source records attributed to Sorensen, J..

6 recordsLinked to original sources

bioRxiv2026

Plasma proteomics identifies an IL-6–associated SAA axis linked to muscle wasting in patients with cancer cachexia

Nearly half of patients with advanced lung cancer develop cachexia, a debilitating syndrome that worsens prognosis. We conducted longitudinal clinical and plasma proteomic profiling of 67 patients with non-small cell lung cancer, with and without cachexia, during first-line treatment. Patients with cachexia at diagnosis exhibited elevated risk of hospitalization and treatment-delaying toxicity. At diagnosis, 128 plasma proteins were upregulated and 67 downregulated in cachectic relative to non-cachectic patients. Longitudinal assessments of body composition, physical performance, metabolism, clinical outcomes, and nutritional risk revealed distinct fat and muscle wasting phenotype trajectories. 71 proteins were associated with fat loss, 92 with muscle loss, and 177 with concurrent muscle and weight loss. We identified and functionally validated 8 plasma proteins linked to muscle loss and adverse clinical outcomes. In a separate cohort of 147 patients with advanced pancreatic cancer receiving the interleukin-6 (IL-6) inhibitor tocilizumab, pharmacological suppression of serum amyloid A (SAA) levels following IL-6 inhibition suggests a systemic IL-6-SAA axis. These results collectively highlight SAA1 and SAA2 as IL-6-driven, cachexia-associated factors that reduce human myotube width. These findings uncover new potential therapeutic targets for cachexia.

Systems Biology↗

bioRxiv2025

Proteomic and phospho-proteomic longitudinal signatures of human skeletal muscle in lung cancer cachexia

Weight loss is a potentially deadly hallmark of many cancers, including lung cancer. In particular, the loss of skeletal muscle mass and function impairs survival and lowers quality of life. Despite being a major determinant of prognosis, the molecular drivers of muscle wasting remain ill-defined. Therefore, there is a critical need for human molecular data to support the development of effective therapies for this currently untreatable condition. Here, we utilize cutting-edge proteomics technology to longitudinally map the proteome and phosphoproteome of skeletal muscle from patients with newly diagnosed, advanced-stage non-small cell lung cancer during their treatment. Leveraging deep in vivo clinical phenotyping of activity, body composition, muscle quality, and nutritional risk, we identified 118/174 muscle proteins/phospho-sites associated with cachexia at diagnosis with indications of sexual dimorphism. Treatment altered 278 proteins and 1,155 phospho-sites, of which 137/91 proteins/phospho-sites were associated with muscle wasting. Our findings highlight disrupted calcium, anabolic, and stress signalling, alongside extracellular matrix and mitochondrial alterations, as key molecular features of cachexia in non-small cell lung cancer. These clinically anchored proteomic and phosphoproteomic signatures provide potential targets for future research.

molecular biology↗

bioRxiv2025

Pathophysiological remodeling of the skeletal muscle microenvironment in patients with lung cancer

Background Muscle wasting, systemic inflammation, and functional decline are highly prevalent and detrimental in patients with advanced-stage non small cell lung cancer (NSCLC). Methods: In this cross sectional study, we investigated NSCLC associated muscle remodeling by analyzing skeletal muscle biopsies from patients with NSCLC (n = 18) and matched controls (n = 18) using quantitative proteomics, histology, fluorescence-activated cell sorting, gene expression profiling, and high resolution respirometry. Findings: NSCLC muscle was characterized by type II muscle fiber atrophy, greater collagen deposition, and redistribution of lipids to the extracellular matrix (ECM), together with remodeling of the inflammatory, immune, ECM and mitochondrial proteome. Additionally, mitochondrial respiratory capacity and morphology were altered in patients with NSCLC, which was associated with increased oxidative stress and dysregulated calcium handling. Concomitantly, we detected STAT3 activation and immune cell alterations, which may negatively impact skeletal muscle health in patients with NSCLC. Finally, we identified a shift in fibro-adipogenic progenitors (FAPs), favoring the CD90 subtype. Mechanistically, conditioned media from patient-derived FAPs reduced myotube width in vitro, uncovering a novel mechanism by which altered paracrine signaling from the muscle resident stromal compartment drives atrophy in cancer cachexia. Interpretation: These findings provide human evidence that altered FAP composition, mitochondrial homeostasis, calcium handling, and immune cell landscape accompany muscle wasting in NSCLC, which may inform therapeutic strategies to preserve skeletal muscle health in patients with cancer.

molecular biology↗

bioRxiv2024

Locally heterogeneous soil viral and prokaryotic responses to prescribed burn correspond with patchy burn severity in a mixed conifer forest

Prescribed burning, a strategy to mitigate wildfires, imparts physicochemical and biological changes to soil. The effects of burns on soil viruses and virus-host dynamics are largely unexplored, despite known viral and prokaryotic contributions to biogeochemical processes. Using a viromic (<0.2 {micro}m size fraction metagenomic) approach, we assessed how viral communities responded to a spring prescribed burn in a mixed conifer forest and whether soil chemical properties and/or prokaryotic host communities could explain the observed patterns. From 120 soil samples (two per depth at 0-3 and 3-6 cm from four burned and two control plots at five timepoints, two before and three after the burn), 91 viromes and 115 16S rRNA gene amplicon libraries were sequenced. Plot location had the greatest effect on explaining variance in viral communities, over treatment (burned or not), depth, and timepoint. Viral and prokaryotic communities exhibited locally heterogenous responses to the fire, with some burned communities resembling unburned controls. This was attributed to patchy burn severity (defined by soil chemistry). Low viromic DNA yields indicated substantial loss of viral biomass in high-severity locations. The relative abundances of Firmicutes, Actinobacteria, and the viruses predicted to infect them significantly increased along the burn severity gradient, suggesting survival of spore formers and viral infection of these abundant, fire-responsive taxa. Our analyses highlight the importance of a nuanced view of soil community responses to fire, not just to burn overall, but to the specific degree of burn severity experienced by each patch of soil, which differed for nearby soils in the same fire.

ecology↗

bioRxiv2023

Exploring viral particle, soil, and extraction buffer physicochemical characteristics and their impacts on extractable viral communities

Soil viruses are expected to be pivotal members of soil ecosystems, and recent advances in viral size fraction metagenomic (viromic) approaches have substantially improved our ability to interrogate soil viral ecology. However, the first step of viromics relies on extraction buffers to effectively remove viral particles from the soil matrix for downstream analysis, and viral extraction efficiency at this stage could be affected by the interplay between viral particles, soils, and extraction buffer chemistry. Here, we investigated whether extraction buffer chemistry affected extractable viral community composition measured by viromics from different soil types, for both biological (samples collected 1 meter apart) and technical (subsamples from the same soil homogenate) replicates. We first investigated protein-supplemented phosphate-buffered saline pH (PPBS, pHs 4.5, 5.5, 6.5, and 7.5) on a forest, grassland and wetland soil that exhibited different soil edaphic properties, and then we tested different buffer chemistries (PPBS, Carbonated Buffer, Glycine, and Saline Magnesium) on just the wetland soil. Spatial distance, or where the sample was taken in the field (i.e., biological replicate), was the primary driver of extractable viral community composition across all buffers and soils tested. Differences in viral community composition according to extraction buffer properties were only observed in the grassland technical replicates at PPBS buffer pH 4.5, as well as in both the wetland technical and biological replicates treated with different buffer chemistries, but the effects of buffer chemistry were secondary to spatial distance in all cases where spatial distance was a factor. The lack of buffering capacity in the grassland soil technical replicates likely increased sorption of some viral particles at pH 4.5, but neither protein composition nor isoelectric point (both calculated bioinformatically) explained this phenomenon. Given that most soil viral ecological studies to date include sample collection schemes over distances much farther apart than the 1-meter distances considered here, results suggest that extraction buffer chemistry is likely of much lower importance than ecological considerations, such as spatial distance, in the design of future soil viral ecological investigations. HIGHLIGHTSO_LISpatial distance was the main driver of extractable viral community composition. C_LIO_LIExtraction buffer chemistry secondarily structured wetland viral communities. C_LIO_LIAt pH 4.5, PPBS buffer likely increased viral sorption in homogenized grassland soil. C_LIO_LIIncreased sorption was not explained by estimated viral protein isoelectric points. C_LI

microbiology↗

bioRxiv2022

Sexually dimorphic neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior

Learning to predict threat is essential but equally important yet often overlooked is learning about the absence of threat. Interrogating neural activity in two nucleus accumbens afferents in male and female mice during aversive and neutral cues reveals sex-specific encoding of cue discrimination and cuemediated suppression of reward behavior. Sexual dimorphisms in neural bases of threat discrimination may reflect sex differences in behavioral strategy relevant to differential psychiatric risk.

neuroscience↗