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).


Congratulations. Our lab have been selected as the 2013 recipient of the Lap-Chee Tsui Publication Award (biomedical research) for our publication “Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer, Science 2013; 339 (6119): 543-548”.

Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion. [Jan, 2014] The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs. We found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation.  Full story can be view in pubmed abstract.

Self-renewal as a therapeutic target in human colorectal cancer. [Jan, 2014] Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Full story can be view in pubmed abstract.

Read more news stories in the archive.