Epigenetic dysregulation is a hallmark of many forms of cancer. But the regulation and pathological consequences of the aberrant epigenetic marks remain to be defined. My research aims to define how changes in the epigenetic landscape influence the initiation and progression of hematological malignancies and identify the biochemical mediators involved in these processes. I have been focusing on several frequently mutated genes in human hematological malignancies including TET2, PHF6 and ASXL1, all of which are involved in the epigenetic machinery. I am also trying to identify pivotal oncogenic lncRNAs in leukemogenesis. Specifically, we are investigating the cellular, molecular and epigenetic mechanisms by which mutations in TET2, PHF6 or ASXL1, or overexpression of oncogenic lncRNAs dysregulate hematopoietic stem/progenitor cells and lead to the pathogenesis of hematological malignancies. State-of-the-art gene-modified mouse models are established to facilitate these studies. My ultimate goal is to translate meaningful basic discoveries into the clinic for novel therapeutic approaches and improved clinical outcomes. These studies will also be of broad significance in advancing our understanding of epigenetic regulation in hematopoiesis and hematopoietic stem cell biology.