I am a pathologist by training with a strong background in clinical hematopathology and basic research. I performed my postdoctoral fellowship in Ben Ebert‘s lab at Harvard Medical School, Brigham and Women’s Hospital, Boston, USA. In my own lab in the department of Developmental Biology at Erasmus MC (Rotterdam), my primary focus is disease-oriented laboratory investigation of clonal myeloid neoplasms, employing a range of genomic technologies as well as classical cellular and molecular biology experimental approaches.
I discovered the first recurrent mutations in a blood cancer called del(5q) MDS. I identified the “Achilles heel” of the mutated cells, which can be used to specifically eliminate these disease-causing cells without affecting normal blood formation – one of the main challenges in cancer research (Schneider et al. Cancer Cell 2014). I further identified that inflammation and activation of the immune system are central mechanisms in the development of a group of blood cancer called myelodysplastic syndrome. Using CRISPR/Cas9-gene editing, I demonstrated that targeting inflammation-inducing “alarmins“ can restore the normal function of diseased hematopoietic cells (Schneider et al. Nature Medicine 2016) – a novel strategy in the treatment. Another major achievement of my laboratory has been the identification of fibrosis-driving cells in an incurable blood cancer called primary myelofibrosis (PMF) (Schneider et al. Cell Stem Cell 2017). I identified new concepts in the diagnosis and treatment of PMF, which are of significant translational value. I received a Starting Grant by the European Research Commission (ERC) to continue this line of research.
My research studies have been considered milestones in the understanding of precursor lesions of blood cancer, were voted as “Best in Hematology” 2014 by the American Society of Hematology, I was honoured with the Tito Bastianello MDS award 2015, the Innovation Award of German Academic Medicine 2016, the Arthur Pappenheim award of the German Society of Hematology 2016, the Johann Georg Zimmermann Award 2017 (European Cancer Research) and the Swammerdam award 2019 of the Dutch Society for Hematology.
Our primary focus is disease-oriented laboratory investigation of clonal myeloid neoplasms, employing a range of genomic technologies as well as classical cellular and molecular biology experimental approaches.
We are particularly interested in dissecting the interaction between hematopoietic cells and the bone marrow niche, in both steady state and myeloid neoplasms. We focus on the role of genetic haploinsufficiency in hematopoietic stem cell biology and targeted therapy of del(5q) myelodysplastic syndrome (Schneider et al. Cancer Cell 2014; Schneider et al. Nature Medicine 2016, Ribezzo et al., Leukemia 2019).
One major achievement of our lab has been the identification of fibrosis-driving cells in primary myelofibrosis (PMF). PMF is an incurable blood cancer that leads to the continuous replacement of blood forming cells in the bone marrow by scar tissue, ultimately leading to failure of the body to produce blood cells and to death (Schneider et al. Cell Stem Cell 2017).
Our recent key finding of Gli1+ cells as fibrosis-driving cells allowed us to dissect the molecular and cellular mechanisms of the fibrotic transformation, specifically highlighting the role of inflammation and the use of the S100A9-inhibitor Tasquinimod (Gleitz et al. Blood, 2020; Leimkühler, Gleitz et al. Cell Stem Cell, 2020). We were able to show that mesenchymal stromal cells are functionally reprogrammed in a stage-dependent manner during fibrosis development; MSCs lose their progenitor status in pre-fibrosis and acquire a pro-fibrotic and inflammatory phenotype in the fibrotic stage. We further aim to understand early forms of BM fibrosis for improved diagnostics in patients, all with the ultimate aim to identify novel therapeutic targets to directly block the cellular and molecular changes occurring in BM fibrosis.
Gleitz HFE et al. Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. 2020
Leimkühler NB, Gleitz HFE, et al. Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis. Cell Stem Cell. 2020
Ribezzo F et al. Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome. Leukemia. 2019
Schneider RK et al. Gli1+ Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an Important Cellular Therapeutic Target. Cell Stem Cell. 2017
Schneider RK et al. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nature Medicine. 2016