Dr. Theocharides Alexandre

Main Field(s) of Research, Abstract
 Myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell (HSC) malignancies mostly of the elderly. Median survival of older AML patients has not changed in the last three decades and accounts for less than 1 year. Similarly, treatment of therapy-resistant and transformed MPN is mostly palliative. In both diseases, cellular subclones that remain unaffected by standard therapy, multiple disease complications and treatment refractoriness are the main cause of death. Therefore alternative therapeutic strategies for MPN and AML are needed.   Recent work by others and myself shows that malignant HSCs are dependent on microenvironmental interactions. My group investigates and therapeutically target extrinsic factors that malignant HSCs require to survive. As murine models only partially reflect the complexity of human disease, a majority of the experiments are performed with primary patient cells in vitro and in vivo in a xenograft model for HSCs. We have access to multiple next-generation immunodeficient mice that the group of Markus Manz (Division of Hematology, University Hospital Zurich) has generated within a consortium. I am also the leading physician of a recently established MPN outpatient clinic in the division of hematology at the University Hospital Zurich. The research platform and the strong interactions with the division of hematology constitute an ideal and attractive infrastructure to assess efficacy of therapeutic compounds and collaborate with the pharmaceutical industry to further translate evidence established in my laboratory to clinical trials.