Dr. Hind Medyouf will be establishing her research team at the Georg-Speyer-Haus starting from October 1st 2014. She will study the molecular mechanisms underlying a heterogeneous group of stem cell driven pre-leukemic syndromes mainly affecting the elderly, referred to as myelodysplastic syndromes (MDS). The group will particularly focus on the complex interplay that Dr. Medyouf recently uncovered between MDS hematopoietic cells and the surrounding stromal cells that constitute the bone marrow microenvironment or “niche”. The overarching goal of the new group is to contribute to our understanding of the biology underlying hematologic malignancies in order to improve the quality of life and survival of patients with blood cancers.
Patients with MDS exhibit ineffective production of mature blood cells, with most patients requiring blood transfusions, a treatment that often results in significant complications (e.g. iron overload). In about 2/3 of the cases the syndromes progressively worsen and lead to bone marrow failure. MDS also has a high propensity to evolve to acute myeloid leukemia (sAML in 1/3 of MDS cases), which is particularly difficult to treat.
During her postdoctoral work with Dr. Andreas Trumpp at the German Cancer Research Centre (Heidelberg, Germany), Dr. Medyouf identified an essential role for niche cells in the maintenance of human MDS stem cells, and used this knowledge to establish unique patient-derived xenograft models. These patient-specific models are the first to allow the study of human MDS in vivo. Moreover, her work revealed the existence of an intricate cross-talk between the diseased hematopoietic cells and their mesenchymal niche counterpart, which likely contributes to human MDS (Cell Stem Cell, 2014). She will now use her expertise and model at the Georg-Speyer-Haus to further delineate the cellular and molecular identity of the disease propagating stem cells and investigate how specific cellular elements and niche factors within the bone marrow microenvironment contribute to MDS pathogenesis and progression. In addition to other model systems (co-culture, genetic mouse models/BMT), these patient-specific xenograft models represent a unique tool for testing new hypotheses related to human MDS biology and an invaluable platform for pre-clinical testing of new therapeutic agents and combination treatments for human MDS.
Because of the pivotal role of niche cells in the control of stem cell function, targeting the interactions between niche and hematopoietic cells represents a particularly attractive opportunity to manipulate the niche support, an approach that is largely under-exploited, in particular in MDS. These future niche mediated-therapies might also be exploited to improve the regenerative abilities of the bone marrow niche to promote hematopoietic reconstitution following stem cell transplantation, the only potential curative treatment for MDS and other leukemias.
Dr. Medyouf received her PhD in “Biology and Biotechnology” from the Paris VII University (France). Her PhD studies revealed the critical role of the Calcineurin/NFAT signaling pathway in pediatric T-cell acute lymphoblastic leukemia (T-ALL) (Nature Medicine, 2007). In 2008, she became an HFSP fellow and moved to work at the Terry Fox Laboratory (Vancouver, Canada) where she demonstrated the prominent role of the IGF/PI3K/AKT signaling axis in T-cell leukemia maintenance (JEM, 2011; Blood, 2010). In 2010, she obtained an EMBO fellowship and moved to the German Cancer Research Centre (Heidelberg, Germany) to study the role of the microenvironment in myelodysplastic syndromes (Cell Stem Cell, 2014). She is currently a holder of a José Carreras Career Award.