Group Allam   Our previous investigations have unveiled a crucial function of Ribonuclease inhibitor (RNH1) in regulating homeostatic hematopoiesis. In the absence of RNH1, the balance in hematopoiesis was skewed significantly to favour myelopoiesis at the expense of lymphoid and erythroid lineage cells. It has also been observed from our in-vivo mice studies that the increase in myelopoiesis however, did not culminate in a leukemic transformation. The ongoing project is aimed at elucidating the mechanism behind the RNH1 mediated exacerbation of myelopoiesis under homeostatic conditions and the implications of genetically modifying RNH1 expression in myeloid malignancies. For this, we are utilizing AML in-vitro (cell lines) and in-vivo (mouse) models along with AML patient derived cells. Our research so far has highlighted an involvement of RNH1 in the AML pathophysiology and ongoing studies are attempted at discerning a therapeutic potential of targeting RNH1 in myeloid malignancies.

Group Riether   The bone marrow (BM) microenvironment is a unique cellular architecture which crucially regulates self-renewal and differentiation potential of hematopoietic stem and progenitor cells through cell-cell interaction or the release of soluble mediators. These evolutionary conserved processes that evolved to protect normal hematopoietic stem cells from elimination and to regulate demand-adapted responses during inflammation are frequently hijacked in cancer and leukemia. The goal of our research is to understand the molecular and cellular mechanisms how different components of the BM microenvironment such as immune cells and stromal cells affect disease-initiating and -maintaining leukemia stem cells (LSCs) and protect them from immune-mediated elimination. We take advantage of state-of-the art technologies, well-established chronic and acute myeloid leukemia mouse and patient-derived xenograft models in order strengthen our understanding on LSCs and to translate our findings into human disease.