The Park Lab studies the molecular mechanisms that regulate normal and malignant stem cells in the blood system. We utilize high-throughput ”-omics” approaches, including RNA-sequencing and proteomic approaches, to identify genes of interest in purified stem cell populations from normal and diseased individuals, and validate genes that mediate disease phenotypes including stem cell function using in vitro systems as well as xenograft and mouse transplantation systems. These approaches have allowed us to accomplish the following: 1) Identification of cell surface antigens present on normal hematopoietic stem cells (HSCs), thereby allowing their prospective separation and investigation; 2) Identification of cell surface antigens present on myeloid disease stem cells, allowing their separation from normal residual hematopoietic stem/progenitor cells. This has led to novel insights regard the mechanisms that regulate disease stem cells and made possible their therapeutic targeting with therapeutic antibodies; 3) Characterization of microRNAs that regulate normal and leukemic stem cell self-renewal and lineage commitment; 4) Isolation of the cell-of-origin in diseases thought to arise in hematopoietic stem/progenitor cells [e.g. acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)] as well as those from mature hematologic malignancies such as hairy cell leukemia (HCL); 5) Discovery of novel genes that regulate HSC aging; 7) Identification of novel chemoresistance mediators in AML; 8) Elucidation of novel pathways that regulate protein translation regulation in HSCs/LSCs.
- • Cancer stem cell antigens for prognostic, diagnostic, and therapeutic use.
- • MicroRNAs that regulate stem cell function.
- • Genes that regulate leukemic stem cell chemoresistance.
- • HSC aging/contribution of aging to hematologic disease.
- • Cell-of-origin studies in hematologic malignancies