Translating genomic discoveries into improved clinical decision making, mechanistic understanding, and therapy of acute leukemia

This research proposal aims to significantly improve the understanding, diagnostics, and treatment of acute leukemia through three aligned projects.

The first project uses multilayer sequencing modalities of primary acute myeloid leukemia (AML) samples to enhance our knowledge of the molecular basis of this malignancy and translate key findings into improved clinical diagnostics.

The second project will study the IGH::DUX4 gene fusion, defining a new subtype of acute leukemia we have described, to understand its mechanistic contribution to acute leukemia.

The third project aims to generate antibodies against two unique targets we have discovered on leukemia stem cells and study their mechanism of action and therapeutic effects in advanced preclinical models.By using multilayer genomic profiling, bioinformatics, and mechanistic studies to molecularly dissect acute leukemia, we aim to make a paradigmatic shift in the way these malignancies are understood at the molecular level and diagnosed in the near future.

By generating antibodies against two newly discovered targets present on AML stem cells and studying their therapeutic effects in advanced preclinical models, this proposal should also accelerate the development of entirely new therapeutics for AML patients.Overall, this research proposal seeks to significantly advance our understanding of acute leukemia and to translate key findings into improved diagnostics and novel therapeutics for AML patients.