Emanuele Murgo

@operapadrepio.it

Department of Medical Sciences, Division of Internal Medicine and Chronobiology Laboratory, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
Gianluigi Mazzoccoli / IRCCS Casa Sollievo della Sofferenza

Emanuele Murgo


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https://researchid.co/emurgo98

RESEARCH, TEACHING, or OTHER INTERESTS

Cancer Research
8

Scopus Publications

Scopus Publications

  • Circadian patterns of growth factor receptor-dependent signaling and implications for carcinogenesis
    Emanuele Murgo, Giorgia Falco, Gaetano Serviddio, Gianluigi Mazzoccoli, Tommaso Colangelo
    Cell Communication and Signaling, 2024
    Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis.
  • The circadian clock circuitry modulates leukemia initiating cell activity in T-cell acute lymphoblastic leukemia
    Emanuele Murgo, Elisabetta De Santis, Francesca Sansico, Valentina Melocchi, Tommaso Colangelo, et al.
    Journal of Experimental and Clinical Cancer Research, 2023
    Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, characterized by restricted cellular subsets with asymmetrically enriched leukemia initiating cell (LIC) activity. Nonetheless, it is still unclear which signaling programs promote LIC maintenance and progression. Methods Here, we evaluated the role of the biological clock in the regulation of the molecular mechanisms and signaling pathways impacting the cellular dynamics in T-ALL through an integrated experimental approach including gene expression profiling of shRNA-modified T-ALL cell lines and Chromatin Immunoprecipitation Sequencing (ChIP-Seq) of leukemic cells. Patient-derived xenograft (PDXs) cell subsets were also genetically manipulated in order to assess the LIC activity modulated by the loss of biological clock in human T-ALL. Results We report that the disruption of the circadian clock circuitry obtained through shRNA-mediated knockdown of CLOCK and BMAL1 genes negatively impacted the growth in vitro as well as the activity in vivo of LIC derived from PDXs after transplantation into immunodeficient recipient mice. Additionally, gene expression data integrated with ChIP-Seq profiles of leukemic cells revealed that the circadian clock directly promotes the expression of genes, such as IL20RB, crucially involved in JAK/STAT signaling, making the T-ALL cells more responsive to Interleukin 20 (IL20). Conclusion Taken together, our data support the concept that the biological clock drives the expression of IL20R prompting JAK/STAT signaling and promoting LIC activity in T-ALL and suggest that the selective targeting of circadian components could be therapeutically relevant for the treatment of T-ALL patients.
  • Role of the Circadian Gas-Responsive Hemeprotein NPAS2 in Physiology and Pathology
    Emanuele Murgo, Tommaso Colangelo, Maria Marina Bellet, Francesco Malatesta, Gianluigi Mazzoccoli
    Biology, 2023
    Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix–loop–helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 is a core cog of the molecular clockwork and plays a regulatory role on metabolic pathways, is important for the function of the central nervous system in mammals, and is involved in carcinogenesis as well as in normal biological functions and processes, such as cardiovascular function and wound healing. We reviewed the scientific literature addressing the various facets of NPAS2 and framing this gene/protein in several and very different research and clinical fields.
  • The circadian clock circuitry deconvolutes colorectal cancer and lung adenocarcinoma heterogeneity in a dynamic time-related framework
    Valentina Melocchi, Roberto Cuttano, Emanuele Murgo, Gianluigi Mazzoccoli, Fabrizio Bianchi
    Cancer Gene Therapy, 2023
  • Noncanonical β-catenin interactions promote leukemia-initiating activity in early T-cell acute lymphoblastic leukemia
    Patrizio Panelli, Elisabetta De Santis, Mattia Colucci, Francesco Tamiro, Francesca Sansico, et al.
    Blood, 2023
    T-cell acute lymphoblastic leukemia (T-ALL) is a T-cell malignancy characterized by cell subsets and enriched with leukemia-initiating cells (LICs). β-Catenin modulates LIC activity in T-ALL. However, its role in maintaining established leukemia stem cells remains largely unknown. To identify functionally relevant protein interactions of β-catenin in T-ALL, we performed coimmunoprecipitation followed by liquid chromatography–mass spectrometry. Here, we report that a noncanonical functional interaction of β-catenin with the Forkhead box O3 (FOXO3) transcription factor positively regulates LIC-related genes, including the cyclin-dependent kinase 4, which is a crucial modulator of cell cycle and tumor maintenance. We also confirm the relevance of these findings using stably integrated fluorescent reporters of β-catenin and FOXO3 activity in patient-derived xenografts, which identify minor subpopulations with enriched LIC activity. In addition, gene expression data at the single-cell level of leukemic cells of primary patients at the time of diagnosis and minimal residual disease (MRD) up to 30 days after the standard treatments reveal that the expression of β-catenin– and FOXO3-dependent genes is present in the CD82+CD117+ cell fraction, which is substantially enriched with LICs in MRD as well as in early T-cell precursor ALL. These findings highlight key functional roles for β-catenin and FOXO3 and suggest novel therapeutic strategies to eradicate aggressive cell subsets in T-ALL.
  • Circadian Genes Expression Patterns in Disorders Due to Enzyme Deficiencies in the Heme Biosynthetic Pathway
    Maria Savino, Claudio Carmine Guida, Maria Nardella, Emanuele Murgo, Bartolomeo Augello, et al.
    Biomedicines, 2022
    Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5′-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.
  • Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock
    Barbara Colombini, Monica Dinu, Emanuele Murgo, Sofia Lotti, Roberto Tarquini, et al.
    Antioxidants, 2022
    Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological reserve in response to stress. Ageing is closely related to oxidative damage and involves immunosenescence and tissue impairment or metabolic imbalances that trigger inflammation and inflammasome formation. One of the main ageing-related alterations is the dysregulation of the immune response, which results in chronic low-level, systemic inflammation, termed “inflammaging”. Genetic and epigenetic changes, as well as environmental factors, promote and/or modulate the mechanisms of ageing at the molecular, cellular, organ, and system levels. Most of these mechanisms are characterized by time-dependent patterns of variation driven by the biological clock. In this review, we describe the involvement of ageing-related processes with inflammation in relation to the functioning of the biological clock and the mechanisms operating this intricate interaction.
  • Early reduction of estimated Glomerular Filtration Rate (eGFR) predicts poor outcome in acutely ill hospitalized COVID-19 patients firstly admitted to medical regular wards (eGFR-COV19 study)
    Francesco Cei, Ludia Chiarugi, Simona Brancati, Maria Silvia Montini, Silvia Dolenti, et al.
    Biomedicine and Pharmacotherapy, 2022