Researcher

    Joey Ghersi , Ph.D.

    joey.ghersi.hsj@ssss.gouv.qc.ca
    Joey Ghersi
    Research Axis
    Fetomaternal and Neonatal Pathologies Axis
    Address
    CHUSJ - Centre de Recherche

    Phone
    514 345-4931 ext.7884

    Title

    • Assistant Professor, Département de pathologie et biologie cellulaire, Université de Montréal (2024)
    • Researcher, Centre de recherche Azrieli du CHU Sainte-Justine (2024)

    Education

    • Stage postdoctoral en biologie du développement et système hémato-vasculaire, Institut cardiovasculaire de Yale, Université de Yale, New Haven, CT, US (2018-2024).
    • Doctorat en biologie du développement et système hémato-vasculaire, Université de Genève, Genève, Suisse (2013-2018).
    • Maitrise en biologie cellulaire et pathologie, Universite Lyon 1, Lyon, France (2011-2013)
    • Licence en biologie de la cellule, Université Lyon 1, Lyon, France (2007-2011)

    Research Interests

    Stem cell populations across tissues, long thought to be homogeneous, have in fact been identified as heterogeneous. Heterogeneity is defined by diverse phenotypic and functional cell characteristics. Stem cell heterogeneity must be properly regulated, or it can lead to lineage-biased progeny and a decreased capacity to repopulate tissues during regeneration. Thus, this presents a significant impediment in biomedical research. 

    Hematopoietic stem cells are heterogenous. Single-cell sequencing analyses show that adult hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous mixture of multipotent stem and progenitor cells that differ in cell cycle status, transcriptional lineage priming, and blood lineage outputs. Reprogramming of somatic cells to HSPCs has been the holy-grail for autologous transplantation, a lifesaving therapy against a variety of blood cancers 

    These cells show variation in self-renewal kinetics and lineage priming biases that can compromise the balanced reconstitution of blood and immune cells after transplantation. Diverse HSPC phenotypes are observed during development in the aorta gonad mesonephros (AGM) of the embryo, where HSPCs are first made. These data suggest that HSPCs are “born heterogeneous”. However, the basis of this intrinsic heterogeneity of HSPCs remains unknown. Uncovering this mechanism will help inform new strategies to regulate HSPC phenotypes ex-vivo and in-vivo. 

    We discovered that signaling in endothelial cells, before the endothelial to hematopoietic transition, regulates HSPC heterogeneity in the embryo and adult zebrafish (Nat Cell Bio, 2023). ​We found that loss of the microRNA in endothelial cells, miR-128, alters the composition of these HSPC states. miR-128 directly inhibits the activity of Wnt- and Notch-signaling in endothelial cells. Mechanistically, single cell RNA-sequencing revealed that Wnt regulation, instructs the transdifferentiation of replicative and erythroid biased HSPCs. In contrast, Notch regulation programs lymphoid biased HSPCs. These results showed that co-ordinate regulation of multiple signaling pathways in endothelial cells, ultimately controls HSPC heterogeneity.

    In the Ghersi lab, we will explore how post-transcriptional and transcriptional mechanisms regulate HSPC heterogeneity at birth. We plan to achieve this goal by uncovering the intrinsic and extrinsic complex regulation in endothelial cells that regulates HSPC heterogeneity.

    Research Topics

    • Hematopoiesis
    • Embryonic Development
    • Zebrafish
    • Cell signaling pathway Endothelial cells

    Career Summary

    Joey Ghersi earned his PhD at the University of Geneva under the supervision of Professor Julien Bertrand, where he discovered a family of new genes, called bif, that controls the production of red blood cells during the embryonic development of zebrafish. Subsequently, he completed a postdoctoral fellowship in Professor Stefania Nicoli's group at Yale University. He identified a microRNA (miR-128) capable of controlling multiple signaling pathways (Wnt and Notch) during the formation of hematopoietic stem cells in zebrafish as well as in a human stem cell system. Additionally, he highlighted that this process is more complex than previously demonstrated. Indeed, he showed that several types of hematopoietic stem cells are formed, and various signaling pathways activation regulate this particular process. Dr. Ghersi was recruited in 2024 as a researcher at the Centre de recherche Azrieli du CHU Sainte-Justine and as an assistant professor in the Department of Pathology and Cell Biology at the University of Montreal.

    Awards and Distinctions

    • Postdoctoral Fellowship, American Heart Association, 2022-2024
    • Travel award and selected speaker at International Vascular Biology meeting (IVBM), Oakland, CA, 2022.
    • Selected speaker at the Ethel Browne Harvey seminar series, Société de biologie du développement (SDB), 2022.

    Publications

    • Ghersi JJ, Baldissera G, Hintzen J, Luff SA, Cheng S, Xia IF, Sturgeon CM, Nicoli S. Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium. Nature Cell Biology, 2023, doi.org/10.1038/s41556-023-01187-9.
    • Kasper DM, Hintzen J, Wu Y, Ghersi JJ, Mandl HK, Salinas KE, Armero W, He Z, Sheng Y, Xie Y, Heindel DW, Park EJ, Sessa WC, Mahal LK, Lebrilla C, Hirschi KK, Nicoli S. The N-glycome regulates the endothelial-to-hematopoietic transition. Science. 2020;370(6521):1186-91. doi: 10.1126/science.aaz2121. PubMed PMID: 33273096. 
    • Ghersi JJ, Mahony CB, Bertrand JY. bif1, a new BMP signaling inhibitor, regulates embryonic hematopoiesis in the zebrafish. Development. 2019;146(6). doi: 10.1242/dev.164103. PubMed PMID: 30837221.
 

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