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”.

Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts. [Jan, 2015] Historically, our understanding of mechanisms underlying human leukemogenesis are inferred from genetically engineered mouse models. Relatively, few models that use primary human cells recapitulate the full leukemic transformation as assayed in xenografts and myeloid transformation is infrequent. Full story can be view in pubmed abstract.

The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. [Jun, 2014] The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis. Full story can be view in pubmed abstract.

Read more news stories in the archive.