JOHN DICK’S  LABORATORY

Publications

View all of John Dick’s publications in Pubmed.

Selected Publications

Kamel-Reid, S. and Dick, JE. Science 1988; 242:1706-1709. This paper reports the first development of an in vivo repopulation assay for human hematopoietic stem cells. With this assay, we went on to identify primitive human hematopoietic cells as measured by repopulation of NOD/SCID mice (termed the SRC). Cell purification and differential retrovirus mediated gene marking showed that SRC were distinct from any other progenitor cell in the hematopoietic system. Collectively, the data reported in a series of papers from my group over the past 15 years have established that the SRC assay is a reliable indicator of human repopulating cells.

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. Nature 1994; 367:645-648. This paper provides the first identification of the human acute myeloid leukemia stem cell using the repopulation assay (termed SL-IC). The discovery of the same type of SL-IC from diverse AML samples suggests that primitive normal human cells and not lineage-committed cells are the target for transformation and that a hierarchy exists in the leukemic clone. Subsequent clonal tracking studies showed that like normal hematopoietic stem cells, there are different types of SC-IC indicating that they still are able to regulate self-renewal machinery. These results establish the similarity between normal and leukemic cell hierarchies. This paper is widely recognized as providing the first direct proof for the cancer stem cell hypothesis and provides the basis for developing novel therapies for their eradication.

Barabé F, Kennedy JA, Hope KJ, Dick JE. Science 2007; 316(5824):600-4. This paper reports the first experimental system to study the leukemogenic process in human cells by introducing oncogenes into primary human progenitors and examining the leukemogenic program that arises. This system provides the means to understand the biological function of any novel stem cell associated genes within a normal human hematopoietic cell and to study the process of human leukemogenesis from the cell of origin to leukemic progression.

McKenzie JL, Gan OI, Doedens M, Wang JC, Dick JE. Nature Immunology 2006; 7:1225-33. This paper reports on the first long-term clonal tracking of human HSC and the discovery of different classes of human stem cells with short- and long-term- repopulating capacity (ST- and LT-SRC, respectively). There was wide variation in proliferation kinetics and self-renewal among SRCs, as well as between SRC daughters that repopulated equivalently, suggesting that SRC fate is unpredictable prior to entering more rigid downstream developmental programs. Moreover, the data reveal maintenance by self-renewing SRCs following an initial period of clonal instability, a result inconsistent with the clonal succession model.

O'Brien CA, Pollett A, Gallinger S, Dick JE. Nature 2007; 4;445(7123):106-10. This paper reports on the identification of a colon cancer-initiating cell that is distinct from the bulk tumour cells. This result provides strong support for the hierarchical organization of human colon cancer. The existence of CSC suggests that for therapeutic strategies to be effective, they must be eradicated.