P1: Dissecting the bone marrow stromal contribution to myelofibrosis

Despite our advanced understanding of mutations occurring in hematopoietic cells in MPN, the specific mechanisms that cause bone marrow fibrosis in primary myelofibrosis (PMF) are not understood, in particular as the cells driving fibrosis have remained obscure for many years and are far less understood than in organ fibrosis. Our recent identification of Gli1+ progenitor cells as a major cellular origin of organ fibrosis and as a relevant therapeutic target to prevent solid organ dysfunction provides significant potential to understand the origin and regulation of fibrosis-driving cells in myelofibrosis. This subproject´s aims are to

  • untangle the mechanism of Gli1+ cell activation using novel genetic tools,
  • dissect the stromal heterogeneity and the contribution of other bone marrow stromal subsets using single cell technologies, and
  • identify novel druggable targets and develop targeted cell-specific therapeutics.
Principal Investigator

Univ.-Prof. Dr. med. Rafael Kramann