Biology subjects

Ojurongbe, O.

Publications and source records attributed to Ojurongbe, O..

4 recordsLinked to original sources

bioRxiv2026

The E2F1 regulon orchestrates a proliferative emergency and vascular programming in fetal endothelial progenitors exposed to GDM: a sex-stratified systems medicine approach

Maternal Gestational Diabetes Mellitus (GDM) and obesity are major drivers of the Developmental Origins of Health and Disease (DOHaD), predisposing offspring to premature cardiovascular disease. However, the specific molecular pathways that program this sex-specific vascular risk remain poorly defined due to the cellular complexity of the placenta. We sought to identify the primary regulatory engines of fetal vascular programming in a sex-stratified neonatal cohort. We analyzed purified neonatal Endothelial Colony Forming Cells (ECFCs)--the fundamental progenitors of the fetal vasculature--from pregnancies complicated by GDM and pre-pregnancy obesity. Using a sex-stratified regulatory inference framework, we decoupled the priming effects of obesity from the acute transcriptomic insult of GDM. Our findings reveal a profound functional asymmetry in fetal vascular adaptation. While male progenitors maintain metabolic resilience through AKT3-mediated buffering, the female fetal-placental interface undergoes a systemic proliferative emergency. This maladaptive state is driven by a massive unshackling of the E2F1-regulon (NES = 16.86), triggered by a maternal-fetal surge in CDK/MAPK signaling. This female-specific program prioritizes unscheduled cell-cycle progression at the metabolic expense of angiogenic maturation and innate immune surveillance. GDM imposes a sex-specific epigenetic scar on female fetal endothelial progenitors, characterized by a quantity-over-quality trade-off in vascular development. This identification of the E2F1-pathway as a driver of fetal vascular exhaustion provides a mechanistic basis for the increased cardiovascular vulnerability in female offspring and identifies the cell cycle as a potential therapeutic target for mitigating the long-term sequelae of GDM.

genomics↗

bioRxiv2026

Comparative pangenomics of Trypanosoma brucei reveal host specialization is driven by targeted or segmental genome streamlining in human and equine-restricted lineages

How the eukaryotic parasite Trypanosoma brucei remodels its genome during host specialization remains a fundamental question in evolutionary biology. In contrast to the uniform, systemic gene loss seen in resident bacterial genomes, the structural variations driving niche restriction in extracellular pathogens are poorly defined. Here, we establish a high-resolution comparative structural pangenomic map of the T. brucei complex. By analyzing the human-restricted specialist DAL972 and the equine-restricted specialist Trypanosoma equiperdum IVM-t1 against the conserved TREU927 backbone, we determine how host-vector constraints dictate eukaryotic genome architecture. Our analyses reveal that host specialization is governed by a coordinated spatial blueprint that segregates structural variation into two distinct evolutionary pathways: targeted perimeter streamlining and systemic core erosion. The human specialist DAL972 preserves its core metabolic toolkit under intense purifying selection, restricting genomic variation to the compartmentalized trimming of its sub-telomeric variant surface glycoprotein (VSG) archives. Conversely, the equine specialist IVM-t1, which has completely abandoned cyclical tsetse fly transmission, displays multi-focal core erosion across internal domains. We demonstrate that vector abandonment forces a shift to strict asexual clonal population dynamics. This transition eases purifying selection, allowing obsolete, insect-stage flagellar and cytoskeletal structures to decay through neutral genetic drift. At the chromosomal perimeters, this structural allocation unmasks an unannotated sub-telomeric reservoir of 86 profile-validated retrotransposon hot spot (RHS) and catalytic DDE transposase domains organized into 23 discrete loci. Operating under adaptive positive selection in the human specialist, these silent, repetitive elements function as physical recombination anchors that stabilize strand exchange. This mechanism drives rapid antigenic diversification while insulating the core genome from dangerous macro-rearrangements. Importantly, we bridge this macro-scale chromosomal architecture to micro-scale proteomic execution through tertiary modeling of these unannotated specialized loci. This structural translation unmasks a biophysical mechanism of structural sequestration, where lineage-specific mutations and specificity-determining positions are deeply buried within hydrophobic protein cores to shield functional divergence from host immune surveillance. By pairing these rigid, hidden core packing networks with hyper-variable surface tiles and dynamic boundary hinges, the parasite deploys tiered molecular mimicry to selectively manipulate host cellular networks. Together, these findings redefine our understanding of structural and non-coding architecture as mechanical drivers of parasitic adaptability, uncovering a direct pipeline from pangenomic spatial variations to stable, structure-based allosteric drug targets.

genomics↗

bioRxiv2025

Continental-scale genomic surveillance of Plasmodium falciparum malaria with rapid nanopore sequencing

In sub-Saharan Africa, continental-scale genomic surveillance of Plasmodium falciparum malaria is needed to track the spread of antimalarial drug resistance and diagnostic test evasion, as well as to monitor parasite evolutionary responses to vaccine rollout. Yet implementation of malaria genomic surveillance at a continental-scale is hindered by resource constraints, the vastness of the continent, and the lack of sequencing protocols suitable for most local laboratories. To address this, we developed an approach to enable a decentralized scale-up of P. falciparum genomic surveillance and established it in six African countries in one year, locally sequencing 1,065 samples. The approach includes a rapid ([~] 5 hours) and cost-efficient (<$25 USD/sample) nanopore sequencing protocol that provides surveillance of drug resistance-associated genes, hrp2/3 deletions, the vaccine target csp, and the polymorphic gene ama1. We coupled this to a bioinformatics dashboard that runs offline on a laptop and displays mapping and variant calling results in real-time. We demonstrate robust sequencing coverage across parasitemia levels and laboratories, accurate identification of antimalarial resistance markers and hrp2/3 deletions; and, with a novel variant caller, sensitive detection of mutations carried by minor clones. Our approach will accelerate genomic surveillance of P. falciparum malaria across sub-Saharan Africa at a time of urgent need.

genomics↗

bioRxiv2022

Transcriptomic analyses of differentially expressed genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection

BackgroundMalaria transmission and endemicity in Africa remains hugely disproportionate compared to the rest of the world. The complex life cycle of P. falciparum (Pf) between the vertebrate human host and the anopheline vector results in differential expression of genes within and between hosts. An in-depth understanding of Pf interaction with various human genes through regulatory elements will pave way for identification of additional tool in the arsenal for malaria control. Therefore, the regulatory elements (REs) involved in the over- or under-expression of various host immune genes hold a key to alternative control measures that can be applied for prompt diagnosis and treatment. MethodsWe carried out an RNAseq analysis to identify differentially expressed genes and network analysis of non-coding RNAs and target genes associated with immune response in individuals with different clinical outcomes. Raw RNAseq datasets, retrieved for analyses include individuals with severe (Gambia - 20), symptomatic (Burkina Faso - 15), asymptomatic (Mali - 16) malaria as well as uninfected controls (Tanzania - 20; Mali - 36). ResultsOf the total 107 datasets retrieved, we identified 5534 differentially expressed genes (DEGs) among disease and control groups. A peculiar pattern of DEGs was observed, with individuals presenting with severe/symptomatic malaria having the highest and most diverse upregulated genes, while a reverse phenomenon was recorded among the asymptomatic and uninfected individuals. In addition, we identified 141 differentially expressed (DE) miRNA, of which 78 and 63 were upregulated and downregulated respectively. Interactome analysis revealed a moderate interaction between DEGs and miRNAs. Of all identified miRNA, five were unique (hsa-mir-32, hsa-mir-25, hsa-mir-221, hsa-mir-29 and hsa-mir-148) because of their connectivity to several genes, including hsa-mir-221 connected to 16 genes. Six-hundred and eight DE lncRNA were identified, including SLC7A11, LINC01524 among the upregulated ones. ConclusionOur study provides important insights into host immune genes undergoing differential expression under different malaria conditions. It also identified unique miRNAs and lncRNAs that modify and/or regulate the expression of various immune genes. These regulatory elements, we surmise have the potential to serve a diagnostic purpose in discriminating between individuals with severe/symptomatic malaria and those with asymptomatic infection or uninfected.

immunology↗