Research We Fund

Clonal hematopoiesis (CH) often precedes AML development, yet the molecular basis of CH expansion and progression to AML remains a mystery. By deploying single-cell DNA methylation analysis of longitudinal human in-vitro and in-vivo CH models, I aim to identify DNA methylation defects promoting CH fitness advantage, specifically in response to chronic inflammation. This will facilitate the design of therapies to halt premalignant clonal expansions and ultimately prevent leukemic transformation.

Clonal cytopenia of undetermined significance (CCUS) is a poorly understood precursor condition linking clonal hematopoiesis with myeloid malignancy. Motivated by human biobank data, I developed a novel murine model of neutropenic CCUS and found interleukin-17A to be necessary and sufficient to propel Tet2-deficient clonal outgrowth. The objectives of this project are to define the drivers of interleukin-17A liberation in neutropenic CCUS and the mechanism by which it hastens clonal progression.

Myelodysplastic syndrome (MDS) is a fatal disease with limited therapeutic opportunities. To increase survival rate, it is essential to identify therapeutic targets specific for MDS stem and progenitor cells (MDS-SC), the source of the disease. MDS-SC uniquely upregulate nicotinamide metabolism. We thus aim to understand its importance on MDS-SC function and survival using multi-omics analysis. Completion of the study will have identified a new treatment modality to improve MDS patient outcome.

Outcomes for children with T-ALL and T-LL have improved, yet prognosis for children with relapsed disease is dismal. A critical gap remains in identifying high-risk patients in order to allocate novel targeted therapies or immunotherapies. Building on prior work, I will utilize comprehensive genomic profiling to examine the impact of genetic ancestry on tumor biology and survival outcomes. My goal is to improve risk stratification, guide targeted therapy, and reduce inequity in T-ALL/T-LL.