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JOHN DICK’S  LABORATORY

Research Focus

Our long-term objectives are to understand the genetic pathways that control human hematopoietic stem cells (HSCs) and to determine how changes in these programs lead to generating leukemic stem cells (LSC). By identifying the target pathways involved in these changes we will be able to contribute to the development of targeted therapeutics.

We have developed novel NOD/SCID xenotransplant assays for human HSCs and primitive progenitors (Nature 1994) and methods for modelling initiation and progression of leukemia through genetic manipulation (Science 2007) that have  provided insight into human hematopoiesis and leukemia development. Using these systems we have been able to interrogate the genetics of leukemia and we have discovered that genetic diversity occurs in functionally defined leukaemia-initiating cells and that many diagnostic patient samples contain multiple genetically distinct leukaemia-initiating cell subclones (Nature 2011).

News

An integrated analysis of heterogeneous drug responses in acute myeloid leukemia that enables the discovery of predictive biomarkers.Many promising new cancer drugs proceed through preclinical testing and early-phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Full Story can be view in pubmed abstract.

miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Full Story can be view in pubmed abstract.

Molecular landscapes of human hematopoietic stem cells in health and leukemia. Blood cells are organized as a hierarchy with hematopoietic stem cells (HSCs) at the root. The advent of genomic technologies has opened the way for global characterization of the molecular landscape of HSCs and their progeny, both in mouse and human models, at the genetic, transcriptomic, epigenetic, and proteomics levels. Full story can be view in pubmed abstract.

Read more news stories in the archive.