Biology subjects

Emery-Corbin, S. J.

Publications and source records attributed to Emery-Corbin, S. J..

4 recordsLinked to original sources

bioRxiv2026

Megakaryocytic proteomic signatures define myeloproliferative neoplasms

The classical Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders of the bone marrow with significant niche dysregulation driven in part by abnormal megakaryocytes. The three classical MPNs: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), display established megakaryocytic morphological differences which aid in their diagnostic classification. The paucity of megakaryocytes in the bone marrow aspirate has previously limited a proteomic analysis of megakaryocytes in clinical samples. We aimed to undertake an unbiased proteomic analysis of in situ megakaryocytes from the bone marrow of patients with PV, ET, and PMF. Using a novel, deep visual proteomics strategy, we dissected and analyzed megakaryocytes from 60 MPN patients and 20 controls (patients with limited stage non-Hodgkin lymphoma who had uninvolved bone marrow). We reveal that megakaryocyte proteomics from MPN patients are distinct to those from control patients, and further, that the megakaryocytes from the three MPNs have unique, disease-specific signatures. The disease-specific megakaryocyte proteome highlights novel pathways of disease.

cancer biology↗

bioRxiv2026

If the shoe fits? -- technical nuances of plasma proteomic workflows in clinical and preclinical contexts

The push for new clinical biomarkers has seen rapid innovation in biofluid analysis, particularly for plasma. For mass-spectrometry (MS)-based analysis, achieving depth and quantitative accuracy whilst ensuring throughput continues to shape plasma methods development. Numerous workflows have emerged that mitigate high-abundance suppression and expand dynamic range, especially when paired with next-generation MS instrumentation. Yet systematic evaluations that also consider biological variables (e.g., biofluid type, species) and technical parameters (e.g., MS methods) are limited. Here, we benchmarked eight sample-preparation workflows spanning neat approaches (SP3, STrap), depletion (perchloric acid, PerCA), and corona-enrichment strategies (MagNet HILIC/SAX, Enrich-iST, ProteoNano). We compared their performance across human plasma, human serum, and rat plasma, analysing all samples on an Orbitrap Astral (Thermo) using two plasma-optimised data-independent acquisition (DIA) methods: one discovery-maximised and one throughput-maximised. We identified 2,726 human and 3,767 rat proteins across workflows and methods, including [~]1,000 from neat plasma. Increasing throughput incurred a [~]20-30% reduction in depth, depending on workflow and species. EV-enrichment produced the deepest proteomes but with distinct compositions relative to neat, depleted, and secreted-protein-enriched samples, revealing a unique sub-proteome niche. Several workflows also performed markedly better in rat plasma, supporting improved sensitivity for preclinical analyses. Enrichment or depletion dramatically reshaped the balance of tissue-and cell-specific proteins detectable in plasma, suggesting that workflow choice should be guided by the organs, immune targets, or inflammatory signals most relevant to the study. In this vein, statistical analysis of differentially abundant proteins showed that >90% of detected proteins were significantly altered between workflows, with the largest numbers arising from the corona-enrichment strategies, underscoring how strongly workflow choice shapes the downstream proteome. Taken together, these findings emphasise a rapidly expanding plasma methodological landscape, where the most effective workflow is the one most precisely tailored to a cohorts biology.

systems biology↗

bioRxiv2025

Host iron deficiency protects against Plasmodium infection and drives parasite molecular reprofiling.

Iron deficiency, anemia and Plasmodium infection represent significant global health challenges with overlapping geographical distributions, particularly affecting pregnant women in Africa, yet the mechanisms underlying their interactions remain poorly understood. We employed a multilayered approach combining clinical data from Malawian pregnant women (n=711) in the REVAMP trial, a genetic mouse model (Tmprss6-knockout), and in vitro P. falciparum cultures to clarify associations between iron status and malaria susceptibility. Iron deficiency was associated with 50% reduced P. falciparum parasitemia in pregnant women (95% CI [30%-64%], p<0.0001), while iron-deficient mice exhibited significantly improved survival against P. berghei (median 15.5 days vs. 7.0 days for WT mice) and protection from cerebral malaria (83% vs 17% survival). Iron chelation induced substantial transcriptomic and proteomic changes in cultured parasites, affecting host cell invasion and nutrient acquisition processes. Importantly, intravenous iron supplementation did not increase subsequent parasitemia when coupled with malaria prevention. These findings demonstrate that iron deficiency protects against Plasmodium infection and support WHO recommendations for iron supplementation in malaria-endemic regions when combined with adequate malaria prevention strategies.

cell biology↗

bioRxiv2021

Population genomics of Cryptosporidium hominis across five continents identifies two subspecies that have diverged and recombined during 500 years of evolution

Cryptosporidiosis is a major global health problem and a primary cause of diarrhoea, particularly in young children in low- and middle-income countries (LMICs). The zoonotic Cryptosporidium parvum and anthroponotic C. hominis cause most human infections. Here, we present a comprehensive whole-genome study of C. hominis, comprising 114 isolates from 16 countries within five continents. We detect two lineages with distinct biology and demography, which diverged circa 500 years ago. We consider these lineages two subspecies and propose the names C. hominis hominis and C. hominis aquapotentis (gp60 subtype IbA10G2). In our study, C. h. hominis is almost exclusively represented by isolates from LMICs in Africa and Asia and appears to have undergone recent population contraction. In contrast, C. h. aquapotentis was found in high-income countries, mainly in Europe, North America and Oceania, and appears to be expanding. Notably, C. h. aquapotentis is associated with high rates of direct human-to-human transmission, which may explain its success in countries with well-developed environmental sanitation infrastructure. Intriguingly, we detected genomic regions of introgression following secondary contact between the subspecies. This resulted in high diversity and divergence in genomic islands of putative virulence genes (GIPVs), including muc5 (CHUDEA2_430) and a hypothetical protein (CHUDEA6_5270). This diversity is maintained by balancing selection, suggesting a coevolutionary arms race with the host. Lastly, we find that recent gene flow from C. h. aquapotentis to C. h. hominis, likely associated with increased human migration, may be driving evolution of more virulent C. hominis variants.

genomics↗