The Park lab studies the molecular and cellular pathogenesis of hematopoietic disorders arising from hematopoietic stem/progenitor cells. We do so by directly comparing purified neoplastic hematopoietic stem/progenitor cells to their normal counterparts and interrogating their function in vivo and in vitro, using primary human cells whenever possible. While in Irving Weissman's lab at Stanford, Dr. Park analyzed microRNA (miRNA) expression in purified human hematopoietic stem cells (HSC) and committed progenitors as well as leukemia-initiating cells, i.e. leukemia stem cells (LSC), in human acute myeloid leukemia (AML). These studies revealed widespread miRNA dysregulation in LSC compared to normal HSC/committed progenitors and resulted in the demonstration that miRNAs may act as oncogenes in human AML. Dr. Park's lab also investigates mechanisms underlying bone marrow failure syndromes, specifically myelodysplastic syndromes. Analysis of purified HSC and committed progenitors from MDS patients revealed widespread dysregulated mRNA expression in MDS, including numerous cell surface proteins and components of the ribosome biogenesis pathway.
Current areas of investigation include:
- Cellular and molecular basis of miR-29a's leukemogenic activity using mouse models and primary AML xenografts,
- The role of miRNAs in HSC and AML LSC function.
- Basis of HSC competition and cell death in MDS, particularly with respect to ribosomal protein deficiency.
- Clinical utility of altered progenitor composition and cell surface markers in MDS as diagnostic/prognostic markers and therapeutic targets.