Biology subjects

Thomas, S. C.

Publications and source records attributed to Thomas, S. C..

5 recordsLinked to original sources

bioRxiv2026

Systemic Cysteine Elevation Sustains T-Cell Activation to Potentiate PD-1 Blockade

Resistance to immune checkpoint inhibition remains a major barrier in pancreatic cancer treatment. Here, we show that concurrent administration of probiotics restores sensitivity to anti-PD-1 therapy in pancreatic cancer mouse models. Mice treated with the combination of anti-PD-1 and probiotics demonstrate robust tumor control, accompanied by enrichment of microbial pathways governing cysteine biosynthesis, elevated serum cysteine levels, and increased T cell function. Serum cysteine levels, rather than intratumoral cysteine concentrations, inversely correlate with tumor burden. Functionally, cysteine directly promotes T cell survival, activation, and cytotoxicity while its restriction induces uncoupled transcriptional-translational stress and impairs T cell function. Oral cysteine supplementation synergizes with anti-PD-1 therapy in pancreatic cancer mice, reducing tumor burden and enhancing intratumoral T cell activation, phenocopying probiotics-mediated immune restoration. These findings suggest systemic cysteine availability as a tractable metabolic target to enhance cancer immunotherapy.

cancer biology↗

bioRxiv2025

Evaluation of a Polarization-Sensitive, Dual-Wavelength Wearable Photoplethysmography Sensor Across a Range of Skin Tones

SignificanceHigh-quality photoplethysmography (PPG) signals are essential for accurate extraction of cardiovascular metrics such as heart rate, heart rate variability, and perfusion index. However, signal degradation for individuals with dark skin tones can compromise PPG quality and pose challenges for equitable sensing. AimWe develop a dual-wavelength, polarization-sensitive PPG device to assess perfusion index (PI) across a range of skin tones. ApproachTo evaluate the impact of polarization on PPG signal quality, we record PI for co-polarized (polarized illumination and parallel-aligned polarized detection), and cross-polarized conditions (polarized illumination and orthogonally aligned polarized detection) at 655 nm and 940 nm in participants representing light, medium, and brown skin tone categories. Skin tone classification are based on the individual typology angle (ITA) values derived from the CIE L*b* color space measurements. ResultsAt 940 nm, light from the cross-polarized light channel significantly increases PI (p < 0.05). At 655 nm, cross-polarization presents a statistically significantly enhanced PI (p < 0.05) relative to light from the co-polarized illumination condition, although the magnitude of the improvement decreases with lighter skin tone indication a possible interaction between skin tone and polarization. This improvement is consistent across all skin tones. ConclusionsOur results suggest that the cross-polarized condition improves PPG signal quality by reducing the influence of superficial scattering and enhancing deeper vascular signals. This approach may be especially beneficial for individuals with darker skin tones and offers a promising path towards more robust and inclusive physiological monitoring using PPG-based technologies.

bioengineering↗

bioRxiv2025

Comparative responses of legume vs. non-legume tropical trees to biochar additions

Nitrogen-fixing plants in the legume family (Fabaceae) may show particularly large positive responses to biochar additions due to their capacity to potentially compensate for reduced N in biochar-amended soils. Prior studies also suggest that biochar may have specific developmental effects on legumes, including increased root nodulation and altered morphology. We examined the growth and morphometric responses of legume and non-legume tropical trees to biochar additions in a common garden pot trial experiment. Four legume species (Acacia auriculiformis, A. mangium, Delonix regia, and Pterocarpus santalinus) and four non-legumes (Eucalyptus alba, Melia azedarach, Swietenia macrophylla, and Syzygium cumini) were compared in terms of sapling responses to additions of a wood-feedstock biochar applied at 10 and 20 t/ha. Overall, strong positive effects of biochar additions on sapling performance were observed, with an average increase of 30% in total biomass and a notable increase in height relative to diameter growth. Species showed pronounced differences in responses, with strong interactive effects of species and biochar treatments on growth metrics. Legume species showed an average increase somewhat greater than non-legumes; however, responses were variable among species, with the two Acacia species showing the largest responses, resulting in a non-significant pattern. A literature-based meta-analysis of tropical and subtropical trees likewise suggests greater biochar responses in legumes, but the analysis also falls short of statistical significance. In addition, experimental results indicate large interactive effects of species and biochar on soil pH and other soil properties. Large growth responses of certain taxa of legumes (and other taxa) to biochar, and pronounced species-specific effects on soil properties, may reflect evolved responses to fire disturbance that can be leveraged in the context of forest restoration and enhanced carbon sequestration in degraded tropical landscapes.

plant biology↗

bioRxiv2025

Identification of a secreted protease from Bacteroides fragilis that induces intestinal pain and inflammation by cleavage of PAR2

Protease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated intestinal proteolysis and PAR2-signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS). To identify potential bacterial regulators of PAR2 activity, we developed a functional assay for PAR2 processing and used it to screen conditioned media from a library of diverse gut commensal microbes. We found that multiple bacteria secrete proteases that cleave host PAR2. Using chemoproteomic profiling with a covalent irreversible inhibitor, we identified a previously uncharacterized Bacteroides fragilis serine protease Bfp1, and showed that it cleaves and activates PAR2 in multicellular and murine models. PAR2 cleavage by Bfp1 disrupts the intestinal barrier, sensitizes nociceptors, and triggers colonic inflammation and abdominal pain. Collectively, our findings uncover Bfp1-mediated PAR2-processing as a new axis of host-commensal-interaction in the gut that has the potential to be targeted for therapeutic intervention in IBD or IBS.

microbiology↗

bioRxiv2020

Radiolabeled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesicles in vivo

Modern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial products in vivo. We show that these novel contrast agents are able to identify E. coli with strain level specificity and other bacteria, such as K. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms.

bioengineering↗