My laboratory has interest and expertise in the stem cell origin of myeloid malignancies. About 10 years ago we started to pursue what was at the time a completely novel concept of “preleukemic stem cells” as the earliest origin of the malignant clone – key to the understanding of the pathogenesis and clonal diversification in leukemia and its treatment and mechanisms of relapse. Past accomplishments and current focus areas of research in my laboratory include: (1) Functional and mechanistic study of (pre-)leukemic stem cells in AML; (2) Target identification and functional validation at the stem cell level in MDS and AML; (3) Preclinical study of novel agents in MDS and AML to provide a rationale for clinical testing; (4) Implementation of stem cell analysis and monitoring (stem cell MRD) into clinical trials of novel therapeutics; (5) Transcriptional and epigenetic characterization and mechanistic study of purified hematopoietic stem and progenitor cells in normal and malignant hematopoiesis. The overarching goal of our work is to improve our understanding of molecular and cellular leukemia pathogenesis, and the development of novel targeted therapeutic approaches.