Institutes

Translational stem cell and leukemia

team-item

Clinical Group Leader

Bernhard Gentner

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Translational stem cell and leukemia Unit is operating at the intersection of science and clinics, with the mission to bring cutting edge science to patients. In particular, the unit cover 3 thematic areas:

  • Functional intra-tumor heterogeneity and determinants of relapse/non-response to treatment in acute leukemia
  • Innovative approaches for ex vivo gene transfer into hematopoietic stem and progenitor cells
  • Genetically-engineered HSPC as an innovative treatment for malignancies

Research activity

  1. Functional intra-tumor heterogeneity and determinants of relapse/non response to treatment in acute leukemia. The group uses microRNA reporters to prospectively identify blast heterogeneity in AML and ALL patients and understand the functional implications of this heterogeneity and its molecular mechanisms. Concepts such as leukemic stem cell hierarchies and subclonal architecture are tested, as well as ways to integrate them into clinical decision making. The unit is implementing novel technologies such as clonal tracking and single cell RNA sequencing to comprehensively address intra-tumor heterogeneity in leukemia.
  2. Innovative approaches for ex vivo gene transfer into hematopoietic stem and progenitor cells. The unit aims to understand the behavior of human HSC in ex vivo culture, to identify cell subsets in which they are enriched during expansion culture and explore culture conditions optimally supporting their expansion. This will provide a platform to tailor and streamline genetic engineering of HSPC for gene editing and gene addition approaches in genetic diseases and cancer.
  3. Genetically-engineered HSPC as an innovative treatment for malignancies. By exploiting the capacity of HSPC to extensively home to tissues including the tumor microenvironment, the unit is bringing a cancer gene therapy approach based on the transplantation of HSPC engineered with a transcriptionally and post-transcriptionally regulated interferon- transgene into the clinics. Researchers are studying, in the context of hematologic malignancies how various cytokines can enhance the induction of anti-tumor immunity in animal models, and how this effect can be potentiated by combination therapies. The group is also exploring novel ways of delivering a genetically-engineered myeloid graft into tumors, by progenitor expansion, local delivery and novel conditioning.