The lab is committed to the development of new therapies against leukemia that are less toxic and more efficacious. We are pursuing this goal by defining AML dependencies on specific chromatin regulators. The overarching goal is to specifically inhibit these chromatin regulators therapeutically in AML.
The menin-MLL interaction was recently shown to be a therapeutic opportunity in various genetic subtypes of AML that controls leukemogenic gene expression. In this project we are addressing detailed questions about the mechanisms involved by using CRISPR-Cas9 negative selection screens and ChIP-sequencing.
The DOT1L chromatin regulatory complex was shown to be a dependency in specific AML subtypes. In this project, we explore DOT1L functions in a broader complement of genetic AML subtypes and explore how it potentially interacts with wildtype MLL to drive leukemia.
No single drug alone is believed to cure leukemia. In this project we are developing synergistic drug combination partners for compounds that target epigenetic mechanisms in AML. Novel combinatorial drug regimens will be tested in preclinical models of various AML subtypes in vitro and in vivo.