Biology subjects

Feeney, A.

Publications and source records attributed to Feeney, A..

4 recordsLinked to original sources

bioRxiv2026

Multi-omic analysis reveals maturation programs in human pluripotent stem cell-derived cardiomyocytes during long-term culture

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold tremendous promise for disease modeling, drug discovery, and cardiac regenerative therapies. However, the immature phenotype of hPSC-CMs remains a major barrier limiting their translational utility. Here, we performed integrated multi-omic profiling to identify molecular pathways and regulatory programs associated with hPSC-CM maturation during long-term culture. hPSC-CMs were cultured for 113 days and analyzed using metabolomics, proteomics, and transcriptomics across progressive stages of maturation. Long-term culture induced widespread multi-omic remodeling, including significant changes in 142/934 metabolites, 550/3,556 proteins, and 2,892/23,309 transcripts from Day 30 to Day 113. Metabolomic analyses revealed early increases in phospholipid biosynthesis and mitochondrial beta oxidation of fatty acids from Day 30 to Day 60, suggesting metabolic priming precedes later maturation events. In contrast, proteomic remodeling was more prominent during later stages of maturation and was characterized by enhanced calcium handling and cell cycle exit. Transcriptomic analyses demonstrated progressive increases in ion channel expression, t-tubule organization, fatty acid metabolism, creatine shuttle pathways, and cell cycle arrest programs. Transcriptomic and integrative multi-omic pathway analyses identified coordinated suppression of TGF{beta}, MAPK, Wnt, and Hedgehog signaling together with activation of integrin-related, respiratory electron transport, muscle contraction, and Slit-Robo signaling pathways during maturation. Moreover, multi-omic transcription factor activity analysis prioritized a GATA4-centered network of putative cardiomyocyte maturation regulators including SOX7, SOX18, TBX2, and ZFPM2 (FOG2). Together, these findings elucidate the degree and pace of hPSC-CM maturation during long-term culture and establish an integrated multi-omic framework for identifying strategies to accelerate hPSC-CM maturation.

Cell Biology↗

bioRxiv2026

Healing helminths: The disease-modifying potential of helminth-derived proteins in animal models of inflammatory disease

Helminths are parasitic worms that secrete a variety of immune-regulating molecules to modulate the hosts inflammatory responses, enabling them to persist within the host over a long period of time, even decades. Their capacity to control host responses has prompted research into helminth-derived molecules as potential therapies for controlling excessive immune and inflammatory activity across a range of diseases. This systematic review with cross-study quantitative analysis aims to synthesize the published data on helminth-derived immunomodulatory peptides/polypeptides/proteins (HDIPs) with a focus on determining the extent of their disease-modifying and anti-inflammatory potential in in vivo animal models of inflammatory disease. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to February 2026, and 65 articles were included after screening. We found that, although the HDIPs were assessed in multiple different disease models, most published studies assessed their potential in mouse models of colitis, asthma, arthritis and sepsis. Twenty species from which >65 isolated HDIPs were derived were tested in these models, with the trematode, Fasciola hepatica, and the nematode, Acanthocheilonema viteae, the most explored species. A common property of the HDIPs was the ability to significantly reduce disease severity across the in vivo animal models of inflammatory disease, underpinned by a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels. Overall, this systematic review with cross-study quantitative analysis not only synthesizes the existing literature in this field but also highlights the disease-modifying and anti-inflammatory potential of HDIPs for a range of diseases in which immunoregulatory therapeutics may improve disease outcomes. It also encourages accelerated advancement of these helminth-derived molecules into first-in-human clinical trials.

immunology↗

bioRxiv2025

The anti-inflammatory potential of helminth-derived peptides/polypeptides: A systematic review in cellular models of inflammation

Helminths are parasitic worms that secrete a plethora of immune regulatory molecules which allow them to dampen inflammatory responses by their hosts immune system to ensure their survival within the host. Their ability to have a compatible existence with their host has led to research into the potential therapeutic effects of helminth-derived molecules for suppression of overactive immune and inflammatory responses in a wide variety of diseases. This systematic review aims to synthesize the published data on helminth-derived peptides/polypeptides (HDPs) with a focus on determining the extent to which they modulate the inflammatory response in in vitro cellular models of inflammation. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to August 2025, and 79 articles were included after screening. We found that most published studies used LPS or Concanavalin A stimulated macrophages, peripheral blood mononuclear cells or dendritic cells as the cellular model of inflammation. Twenty helminth species from which >60 isolated HDPs were derived were tested in these models, with the nematodes, Haemonchus contortus and Acanthocheilonema viteae, and the trematode, Fasciola hepatica, the most explored species. A common property of these molecules was to ability to significantly reduce the expression or production of pro-inflammatory cytokines such as IL-12, IL-1{beta}, IL-6 and TNF, and significantly increase the expression or production of anti-inflammatory cytokines such as IL-10, TGF{beta} and IL-4. The effects on other cytokines, including IFN{gamma} which is known to have both pro- and anti-inflammatory effects, were less consistent, with HDPs either decreasing or increasing the levels of this cytokine. This systematic review synthesizes the existing literature in this field and shows that the HDPs secreted by several helminth species have consistently demonstrated effects though modification of cytokine levels and, as such, have therapeutic potential in conditions in which overactive immune and inflammatory responses play a pathogenic role.

immunology↗

bioRxiv2022

An Igh novel enhancer modulates antigen receptor diversity by determining locus conformation

The Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of novel enhancers (NEs) that collaborate to configure the locus, determine transcriptional potential in over a hundred functional VH genes and their usage in V(D)J recombination. NE1 engages in a network of long-range interactions that interconnect the subTADs and the recombination center at the DHJH gene cluster. Deletion of NE1 alters discrete chromatin loops, higher order locus conformation, locus-wide VH gene transcription and regional V gene utilization that is linked to a greatly reduced splenic B1 B cell compartment. NE1 blocks long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant VH genes to the recombination center. NE1 is a critical architectural element that coordinates chromatin conformational states that favor VH gene transcription or V(D)J rearrangement.

immunology↗