Our lab is interested in understanding the epigenetic mechanisms driving leukemia development and uncovering novel therapeutic targets using in vitro and in vivo models of acute myeloid leukemia (AML). This project will focus on the epigenetic complexes that cooperate with the oncogene NPM1c to drive oncogenic gene expression. We have previously shown that NPM1c is highly dependent on the MLL histone methyltransferase complex and based on our studies novel targeted therapy approaches are currently in phase II clinical trials (Uckelmann et al. Science 2020). Our recently published study further shows that NPM1c, which was previously been thought to mainly act in the cytoplasm of cancer cells, is present in the nucleus and recruited to chromatin where it directly regulates oncogenic gene expression (Uckelmann et al. Cancer Discovery 2023). In our future studies we will take a closer look at cooperating partners of NPM1c on chromatin to uncover novel epigenetic mechanisms to uncover specific vulnerabilities of preleukemic and leukemic cells. More information can be found here: www.uckelmannlab.com Explore epigenetic complexes driving cancer development using in vitro and in vivo leukemia models Use CRISPR gene editing to generate new model systems - such as endogenous degrader models and reporter cell lines - to study the molecular mechanisms of carcinogenesis Apply cutting edge technologies to study epigenetic and transcriptional deregulation in cancer Identify potential new drug targets and novel treatment approaches for acute myeloid leukemia Develop new ideas to tackle unexplored questions