La rete di data steward: l’esperienza di UniBO

Come rafforzare il supporto alla gestione FAIR dei dati della ricerca e sviluppare una cultura di Open Science all’interno di un Ateneo? Una risposta unica non esiste. L’Università di Bologna si è messa in gioco e, dopo aver inserito questi obiettivi all’interno del piano strategico per il quinquennio 2022-2027, ha lanciato un progetto, chiamato “Data Steward@Unibo”, sperimentando una possibile via per supportare i ricercatori e rafforzare la consapevolezza di una corretta gestione dei dati di ricerca. Il primo passo è stato dotarsi di professionisti, “data steward”, esperti nei diversi domini di ricerca, con esperienza nella gestione FAIR dei dati e nelle tematiche di Open Science. Il talk vuole essere l’occasione per condividere obiettivi e azioni del progetto, presentare i primi risultati di questa esperienza e le prospettive future

NYMPHE Experience - managing data in Horizon project

La presentazione illustra la strategia di Gestione dei dati della Ricerca adottata all'interno del progetto europeo Nymph

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis

Ewing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of EWS progression. The aim of this study was to further define the role of IGF2BP3 in EWS progression. We demonstrated that high IGF2BP3 mRNA expression levels correlated with EWS metastasis and disease progression in well-characterized EWS tumor specimens. EWS tumors with high IGF2BP3 levels were characterized by a specific gene signature enriched in chemokine-mediated signaling pathways. We also discovered that IGF2BP3 regulated the expression of CXCR4 through CD164. Significantly, CD164 and CXCR4 colocalized at the plasma membrane of EWS cells upon CXCL12 stimulation. We further demonstrated that IGF2BP3, CD164, and CXCR4 expression levels correlated in clinical samples and the IGF2BP3/CD164/CXCR4 signaling pathway promoted motility of EWS cells in response to CXCL12 and under hypoxia conditions. The data presented identified CD164 and CXCR4 as novel IGF2BP3 downstream functional effectors indicating that the IGF2BP3/CD164/CXCR4 oncogenic axis may work as critical modulator of EWS aggressiveness. In addition, IGF2BP3, CD164, and CXCR4 expression levels may constitute a novel biomarker panel predictive of EWS progression

Engagement of CD99 activates distinct programs in Ewing sarcoma and macrophages

Ewing sarcoma (EWS) is the second most common pediatric bone tumor. The EWS tumor microenvironment is largely recognized as immune-cold, with macrophages being the most abundant immune cells and their presence associated with worse patient prognosis. Expression of CD99 is a hallmark of EWS cells, and its targeting induces inhibition of EWS tumor growth through a poorly understood mechanism. In this study, we analyzed CD99 expression and functions on macrophages and investigated whether the concomitant targeting of CD99 on both tumor and macrophages could explain the inhibitory effect of this approach against EWS. Targeting CD99 on EWS cells downregulated expression of the "don't eat-me" CD47 molecule but increased levels of the "eat-me" phosphatidyl serine and calreticulin molecules on the outer leaflet of the tumor cell membrane, triggering phagocytosis and digestion of EWS cells by macrophages. In addition, CD99 ligation induced reprogramming of undifferentiated M0 macrophages and M2-like macrophages toward the inflammatory M1-like phenotype. These events resulted in the inhibition of EWS tumor growth. Thus, this study reveals what we believe to be a previously unrecognized function of CD99, which engenders a virtuous circle that delivers intrinsic cell death signals to EWS cells, favors tumor cell phagocytosis by macrophages, and promotes the expression of various molecules and cytokines, which are pro-inflammatory and usually associated with tumor regression. This raises the possibility that CD99 may be involved in boosting the antitumor activity of macrophages

Dai principi alla pratica: gestire i dati della ricerca

Nell’ambito del ciclo “Open Science Corner”, che affronta le buone pratiche alla base della corretta gestione del dato di ricerca, l’incontro “Dai principi alla pratica: gestire i dati della ricerca” intende partire dalle definizioni dei concetti fondamentali per offrire ai ricercatori una panoramica su come orientarsi nella gestione dei dati di ricerca

Dissecting the role of IGF2BP3 in the stress-adaptive response and in intercellular communication in Ewing Sarcoma.

Tumor microenvironment has emerged as key factor influencing tumor progression and metastatization. In this context, small vesicles produced by cancer cells can influence the fate of their surroundings via the horizontal transfer of specific molecular cargos. Ewing Sarcoma, the second most common bone tumor in young patients, presents early metastasis associated to worse prognosis. The RNA binding protein Insulin-like Growth Factor 2 mRNA Binding Protein 3 (IGF2BP3) exerts a pro-oncogenic role associated with metastasis formation and worse prognosis in Ewing Sarcoma. Our aim was to investigate the still unexplored role of IGF2BP3 in the stress-adaptive response to tumor microenvironment and in the interactions between Ewing Sarcoma cells. Hypoxia is a major feature of Ewing Sarcoma microenvironment and we demonstrated that IGF2BP3 can direct the CXCR4-mediated migratory response to CXCL12 in Ewing Sarcoma cells subjected to oxygen deprivation. We also discovered that the interaction between IGF2BP3 and CXCR4 is regulated through CD164 and which colocalize at plasma membrane level, upon CXCL12 exposure. Interestingly, high IGF2BP3 levels in Ewing Sarcoma metastatic lesions positively correlated with the expression of both CD164 and CXCR4, indicating the IGF2BP3/CD164/CXCR4 oncogenic axis as a critical modulator of Ewing Sarcoma metastatic progression. We demonstrated for the first time that IGF2BP3 is loaded into Ewing Sarcoma derived exosomes, accordingly to its cellular levels. We discovered that IGF2BP3+ exosomes carry high levels of IGF2BP3-client mRNAs involved in cellular migration, CD164 and IGF1R, and, by transferring this cargo, sustain the migratory abilities of receiving cells, induce a sharp up-regulation of CD164, CXCR4 and IGF1R and enhance the activation of AKT/mTOR and ERK down-stream signalling pathways. We demostrated that the pro-tumorigenic role of IGF2BP3 is not only exerted at cellular level, but that intercellular communication is crucial in the context of Ewing Sarcoma microenvironment

Research Data Management e principi di Open Science Formazione PhD_v1_16112023

Il dataset contiene le slides delle presentazioni esposte durante il corso online "Research Data Management e Principi di Open Science", erogato dai Data Stewards dell’Università di Bologna e dall’avvocato Francesco Di Tano ai dottorandi dell'Università di Bologna nel mese di ottobre 2023. Il dataset contiene 4 sottocartelle, una per ognuna delle 4 aree tematiche disciplinari a cui è stata erogata la formazione (Area Medico/Scientifica, Area Sociale, Area Tecnologica, Area Umanistica). In ciascuna delle sottocartelle sono presenti i materiali utilizzati per le lezioni di ciascuno dei tre moduli didattici. Modulo 1 "I dati della ricerca: cosa sono e come gestirli" (3h), che comprende quanto segue: - i dati: cosa sono e qual è il loro valore; - i principi fondamentali dell'Open Science e della gestione FAIR dei dati di ricerca; - introduzione alla gestione dei dati di ricerca. (files intitolati “Modulo1_PhD_Formazione_ecc”) Modulo 2 "La gestione dei dati di ricerca: strumenti, azioni e punti chiave" (2,5 ore), che copre i seguenti aspetti: - approfondimento delle fasi e degli strumenti della gestione dei dati di ricerca; - focus: gestione e conservazione dei dati personali. (files intitolati “Modulo2_PhD_Formazione_ecc” e “Modulo2_PhD_Privacy_ecc”) Modulo 3 "Il piano di gestione dei dati: uno strumento utile per la ricerca" (3 ore), che comprende quanto segue: - il Piano di Gestione dei Dati (DMP): cos'è e qual è il suo ruolo nella ricerca; - cosa includere in un DMP e come scriverlo. (files intitolati “Modulo3_PhD_Formazione_ecc”) I materiali dei moduli 1 e 3 si differenziano a seconda dell’area tematica, mentre quelli del modulo 2 sono comuni. Il materiale consiste nei set di slides utilizzati per condurre le lezioni, con riferimenti a materiale utile per l’approfondimento a posteriori delle tematiche trattate nella singola lezione e nel corso in generale. Il target a cui si rivolge il materiale all’interno del dataset è quello degli studenti di dottorato/i ricercatori con poca/nessuna esperienza sulle tematiche di Research Data Management, dati FAIR e Open Science. Il materiale può essere di interesse anche per potenziali formatori su questi argomenti

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis

Ewing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of EWS progression. The aim of this study was to further define the role of IGF2BP3 in EWS progression. We demonstrated that high IGF2BP3 mRNA expression levels correlated with EWS metastasis and disease progression in well-characterized EWS tumor specimens. EWS tumors with high IGF2BP3 levels were characterized by a specific gene signature enriched in chemokine-mediated signaling pathways. We also discovered that IGF2BP3 regulated the expression of CXCR4 through CD164. Significantly, CD164 and CXCR4 colocalized at the plasma membrane of EWS cells upon CXCL12 stimulation. We further demonstrated that IGF2BP3, CD164, and CXCR4 expression levels correlated in clinical samples and the IGF2BP3/CD164/CXCR4 signaling pathway promoted motility of EWS cells in response to CXCL12 and under hypoxia conditions. The data presented identified CD164 and CXCR4 as novel IGF2BP3 downstream functional effectors indicating that the IGF2BP3/CD164/CXCR4 oncogenic axis may work as critical modulator of EWS aggressiveness. In addition, IGF2BP3, CD164, and CXCR4 expression levels may constitute a novel biomarker panel predictive of EWS progression

Supplementary Figure 3 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages

Supplementary Figure 3</p

Supplementary Figure 2 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages

Supplementary Figure 2</p