Research We Fund

The cohesin and BAF complexes are both epigenetic regulators of dynamic chromatin accessibility. Recurrent mutations are observed in proteins of both complexes in adverse risk acute myeloid leukemia (AML). We will use Stag2 (cohesin) and Arid1a (BAF) knockout mice and AML cell lines to deconvolve their unique and cooperative roles in hematopoiesis. This proposal will test the hypothesis that their overlapping functions constitute viable therapeutic targets for these recalcitrant patients.

This research proposal will investigate the role of ubiquitin-based protein degradation in acute myeloid leukemia (AML). Specifically, we will assess the function of the E3 ligase DCAF15 in the development and maintenance of AML. Additionally, we will evaluate DCAF15 as a potential therapeutic target for AML treatment. The outcomes of this project aim to provide a better understanding of AML pathogenesis and create opportunities for personalized therapy.

Loss of chromosome Y (LOY) is common in acute myeloid leukemia (AML) yet the mechanistic and therapeutic roles of LOY remain largely unexplored. Using CRISPR-Cas9 genetic perturbation, I will interrogate individual genes and whole chromosome Y loss in models of pre-leukemic progenitor and human AML cells to determine necessary and sufficient contributors of LOY to phenotypes. This will enable discovery of novel treatment opportunities conferred by loss of chromosome Y.

This study aims to explore how mutant SETBP1 affects histone methyltransferase complexes to drive leukemia-associated gene transcription. I will use biochemical, imaging, and epigenetic methods to assess the effects of SETBP1 mutations on complex formation, genomic localization, and function. I will evaluate if inhibitors can disrupt SETBP1-driven oncogenesis in human leukemia cell lines, hematopoietic cells, and patient samples to identify novel therapeutic targets in SETBP1-mutant leukemias.