Biology subjects

Pearce, E.

Publications and source records attributed to Pearce, E..

5 recordsLinked to original sources

bioRxiv2026

Monocytes are biological sensors of aging and frailty in humans

Among older adults, frailty is clinically identifiable and characterized by increased vulnerability to adverse health outcomes. Although various tools exist to identify frailty, diagnosis often depends on late-stage clinical symptoms, which typically limit proactive intervention options. We considered whether aging and frailty information may be encoded in the single-cell behaviors and dynamic responses of primary human monocytes. Combining high-content imaging, single-cell behavior profiling, and machine learning, we demonstrated unique age- and frailty-dependent monocyte behaviors at baseline and following exposure to inflammatory stressors. Using these single-cell behaviors, we developed a deep learning neural network model called scTRAIT. scTRAIT accurately predicts the frailty status of older donors, including the capability to track and forecast longitudinal changes in frailty status. Collectively, these findings demonstrate that aging and frailty information are robustly encoded within single-cell behaviors, establishing monocytes as significant biological sensors of aging and frailty in humans. TeaserSingle-cell monocyte responses enable robust prediction of aging and frailty in humans

bioengineering↗

bioRxiv2025

TOWARDS CLIMATE-SMART REWILDING: AN INTEGRATED FRAMEWORK FOR BIODIVERSITY, CLIMATE CHANGE, AND SOCIETY

The UN Decade on Ecosystem Restoration and the Kunming-Montreal Global Biodiversity Framework aim to restore 30% of degraded ecosystems. Both the IPCC and IPBES highlight the crucial role of ecosystem restoration in addressing the interconnected crises of climate change and biodiversity loss. One key restoration strategy is rewilding, which enhances ecosystem complexity with minimal human intervention. While traditional rewilding strategies often focus on benefits for biodiversity, we propose a climate-smart rewilding framework as a new approach designed to deliver climate benefits alongside biodiversity restoration. This framework seeks to integrate biodiversity, climate change adaptation and mitigation, as well as socio-economic benefits and trade-offs. We illustrate how this framework can be utilized to identify areas across Europe where rewilding could increase carbon sequestration, enhance species abilities to adapt to the velocity of climate change, and maximize wildlife-watching benefits while minimizing the costs associated with livestock-wildlife conflict. Finally, we acknowledge some limitations of climate-smart rewilding, but we argue that its adaptability and low cost render it a promising solution to the challenges facing Europe and beyond.

ecology↗

bioRxiv2023

Electrostatic encoding of genome organization principles within single native nucleosomes

The eukaryotic genome, first packed into nucleosomes of about 150 bp around the histone core, is organized into euchromatin and heterochromatin, corresponding to the A and B compartments, respectively. Here, we asked if individual nucleosomes in vivo know where to go. That is, do mono-nucleosomes by themselves contain A/B compartment information, associated with transcription activity, in their biophysical properties? We purified native mono-nucleosomes to high monodispersity and used physiological concentrations of biological polyamines to determine their condensability. The chromosomal regions known to partition into A compartments have low condensability and vice versa. In silico chromatin polymer simulations using condensability as the only input showed that biophysical information needed to form compartments is all contained in single native nucleosomes and no other factors are needed. Condensability is also strongly anticorrelated with gene expression, and especially so near the promoter region and in a cell type dependent manner. Therefore, individual nucleosomes in the promoter know whether the gene is on or off, and that information is contained in their biophysical properties. Comparison with genetic and epigenetic features suggest that nucleosome condensability is a very meaningful axis onto which to project the high dimensional cellular chromatin state. Analysis of condensability using various condensing agents including those that are protein-based suggests that genome organization principle encoded into individual nucleosomes is electrostatic in nature. Polyamine depletion in mouse T cells, by either knocking out ornithine decarboxylase (ODC) or inhibiting ODC, results in hyperpolarized condensability, suggesting that when cells cannot rely on polyamines to translate biophysical properties of nucleosomes to control gene expression and 3D genome organization, they accentuate condensability contrast, which may explain dysfunction known to occur with polyamine deficiency.

biophysics↗

bioRxiv2020

Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs

Plasma-derived polyclonal antibodies are polyvalent drugs used for many important clinical indications that require modulation of multiple drug targets simultaneously, including emerging infectious disease and transplantation. However, plasma-derived drugs suffer many problems, including low potency, impurities, constraints on supply, and batch-to-batch variation. In this study, we demonstrated proofs-of-concept for a technology that uses microfluidics and molecular genomics to capture diverse mammalian antibody repertoires as multivalent recombinant drugs. These "recombinant hyperimmune" drugs comprised thousands to tens of thousands of antibodies and were derived from convalescent human donors, or vaccinated human donors or immunized mice. Here we used our technology to build a highly potent recombinant hyperimmune for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in less than three months. We also validated a recombinant hyperimmune for Zika virus disease that abrogates antibody-dependent enhancement (ADE) through Fc engineering. For patients with primary immune deficiency (PID), we built high potency polyvalent recombinant hyperimmunes against pathogens that commonly cause serious lung infections. Finally, to address the limitations of rabbit-derived anti-thymocyte globulin (ATG), we generated a recombinant human version and demonstrated in vivo function against graft-versus-host disease (GVHD). Recombinant hyperimmunes are a novel class of drugs that could be used to target a wide variety of other clinical applications, including cancer and autoimmunity.

immunology↗

bioRxiv2020

Metabolic and Epigenomic Regulation of Th17/Treg Balance by the Polyamine Pathway

Cellular metabolism can orchestrate immune cell function. We previously demonstrated that lipid biosynthesis represents one such gatekeeper to Th17 cell functional state. Utilizing Compass, a transcriptome-based algorithm for prediction of metabolic flux, we constructed a comprehensive metabolic circuitry for Th17 cell function and identified the polyamine pathway as a candidate metabolic node, the flux of which regulates the inflammatory function of T cells. Testing this prediction, we found that expression and activities of enzymes of the polyamine pathway were enhanced in pathogenic Th17 cells and suppressed in regulatory T cells. Perturbation of the polyamine pathway in Th17 cells suppressed canonical Th17 cell cytokines and promoted the expression of Foxp3, accompanied by dramatic shift in transcriptome and epigenome, transitioning Th17 cells into a Treg-like state. Genetic and chemical perturbation of the polyamine pathway resulted in attenuation of tissue inflammation in an autoimmune disease model of central nervous system, with changes in T cell effector phenotype.

immunology↗