New Investigator Research Grant Program

Myelodysplastic neoplasms (MDS) are complex and often fatal blood cancers believed to originate from cancer stem cells (CSCs) that drive disease progression and treatment resistance. CSCs evolve from healthy blood-forming stem cells (HSCs) in the bone marrow. With aging, HSCs can acquire mutations, leading to clonal hematopoiesis (CH)—a pre-cancerous condition that increases MDS risk. However, how mutated HSCs transform into MDS-CSCs remains poorly understood, hindering our ability to detect and eliminate these cells early. Past studies struggled to isolate these rare cells, limiting understanding of MDS development and therapy design. To address this, I used machine learning and advanced single-cell technologies to identify MDS-CSCs with a unique surface signature. These cells predict worse outcomes and show elevated inflammation-related activity. Notably, DAPK1 is highly active in MDS-CSCs, CH-HSCs, and aging HSCs compared to young, healthy cells. Excitingly, a DAPK1 inhibitor significantly reduces MDS cell proliferation while sparing healthy cells. With support from the Leukemia Research Foundation, my lab at Stanford will use cutting-edge single-cell analysis, lineage tracing, and patient samples transplanted into mice to validate these CSC markers and evaluate DAPK1 as a therapeutic target. This work will provide the foundation for clinical trials to improve disease monitoring and develop new targeted therapies, ultimately benefiting MDS patients.