Post-Doctoral Fellowship in Oncogenic Deregulation of Lymphoid Lineage Specification

Job description

The Normal and Pathological Lymphoid Differentiation Laboratory from the Institut Necker Enfants Malades (INSERM UMR 1151 Research Center) is seeking to welcome a PhD trained in hematopoietic stem cell biology and/or translational leukemia research.

Our laboratory investigates the interface between normal and leukemic lymphoid development. We combine dual expertise in oncogenesis and developmental immunology to dissect the transcriptional and epigenetic events underlying oncogenic arrest during the specification of hematopoietic stem cells (HSC) toward the lymphoid lineage. Our research uses in vivo (HSC xenografts; PDX) and in vitro cellular (multi-lineage diff. assays) and molecular (scRNA sequencing, methylome profiling, genome-wide HiC, CUT&Tag) approaches through which understanding the malignant deregulation of early hemato-lymphopoiesis can lead both to targeted and personalized therapeutics. The specific aims of the current research projects are: (i) to decipher the hierarchy of transcription factors and epigenetic regulators controlling the specification of human HSCs toward the lymphoid lineage; (ii) to characterize the 3D genome alterations caused by oncogenes involved in the pathogenesis of immature T-cell acute lymphoblastic leukemia.

The “Institut Necker Enfants Malades” (INEM), located on the Necker Hospital Campus (Paris) provides an exceptional scientific and academic environment. Administered jointly by INSERM, CNRS and the Université Paris Cité, INEM benefits from close contacts with clinicians and state-of-the-art technological platforms in one of France’s foremost research centered universities.\r\n

The successful candidate will be offered a 24-to-36-month contract with salary depending on experience. This position is available immediately, though start date is flexible.

Bruno CANQUE, M.D., Ph.D. and Vahid ASNAFI, M.D., Ph.D.

References :

Alhaj Hussen, K., et al. (2017). Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis. Immunity 47, 680-696 e688. 10.1016/j.immuni.2017.09.009.

Cieslak, A., et al. (2020). Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation. J Exp Med 217. 10.1084/jem.20192360.

Andrieu, G.P, et al. (2021). PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL. Blood 138, 1855-1869. 10.1182/blood.2020010081.

Touzart, A., et al. (2021). Epigenetic analysis of patients with T-ALL identifies poor outcomes and a hypomethylating agent-responsive subgroup. Science translational medicine 13. 10.1126/scitranslmed.abc4834

Keita, S., et al. (2023). Distinct subsets of multi-lymphoid progenitors support ontogeny-related changes in human lymphopoiesis. Cell Rep 42, 112618. 10.1016/j.celrep.2023.112618.

Requirements

Highly motivated candidates with a Ph.D. or M.D./Ph.D. in developmental immunology and/or hematology are welcome to apply. Applicants should possess strong laboratory, analytical, interpersonal and communication skills. Candidates with previous experience in stem cell biology, multi-omics and statistics are highly desirable.

How to apply

Interested candidates should email a brief cover letter indicating their research interests, experience and career goals, CV, and contact information for 2 references to Pr Bruno Canque.

e-mail: bruno.canque@ephe.psl.eu