Yu-Hsiang Chen, MS, PhD
Deciphering the Molecular Pathways Governing the Progression of MRD in MDS
Abstract
Myelodysplastic syndromes (MDS) involve ineffective hematopoiesis and transformation into acute myeloid leukemia due to mutations in hematopoietic stem and progenitor cells. Allogeneic hematopoietic stem cell transplantation (SCT) is the sole curative approach, leveraging the graft-versus-leukemia effect by donor T cells. MDS relapse, driven by measurable residual disease (MRD) persistence, is the major obstacle to curative outcomes after SCT, but the underlying mechanistic pathways remain incompletely understood. Here, we propose to unravel the molecular drivers of MRD progression following SCT using a novel single-cell workflow, CARAMEL-seq, to simultaneously capture transcriptomic, protein, chromatin, and genotype data. From uniquely annotated, longitudinal biorepositories, we will use cutting-edge machine learning algorithms to illuminate the pathways that MDS cells use to escape immune cell killing and nominate therapeutic targets to halt MRD progression.
The PhRMA Foundation award provides me with the essential resources to advance my research on characterizing measurable residual disease in blood cancer and monitoring its evolution, along with immune cell interactions, after allogeneic stem cell transplantation. This support strengthens our mission to make a meaningful impact on cancer diagnosis and treatment.
