New Investigator Research Grant Program

Myelodysplastic syndromes (MDS) are a group of blood disorders driven by abnormal hematopoietic stem and progenitor cells (HSPCs). Despite current treatments, these cells often persist after therapy, making MDS difficult to cure and more likely to progress. Understanding why disease-sustaining cells survive over time is therefore critical for improving treatment for patients with MDS. Our research suggests that the persistence of MDS HSPCs may rely on two protective mechanisms. One is an internal stress-adaptation program involving ClpP, a protease that helps maintain mitochondrial protein quality and function. The other is external support from the bone marrow microenvironment, particularly inflammatory signals such as IL-1-related pathways, which may further protect disease-sustaining cells. Based on these findings, this study focuses on a new persistence-defense axis, in which cell-intrinsic mitochondrial stress adaptation and microenvironmental inflammatory support work together to sustain MDS HSPCs. We will investigate whether disrupting both layers of this protective system can lead to more effective strategies for weakening disease-sustaining cells. By clarifying these critical processes, this research may provide a biological foundation for developing rational, disease-modifying therapeutic strategies to improve clinical outcomes for patients with MDS.