Researcher biography

Dr Slape completed his Ph.D. studies at The Queen Elizabeth Hospital campus of The University of Adelaide Department of Medicine in 2003, on a project involving the mapping of breakpoints of leukemic chromosomal translocations under the supervision of Dr Alex Dobrovic. Dr Slape then did post-doctoral work at the National Cancer Institute at the National Institutes of Health in Bethesda, Maryland, USA where he worked in the laboratory of Dr Peter Aplan. Here he generated and characterised the NUP98-HOXD13 mouse model of myelodysplasia, the first mouse model of this disease and still one of the best and most-used around the world. Returning to Australia in 2008, Dr Slape worked at the Bone Marrow Research Laboratories at the Royal Melbourne Hospital, where he initiated projects investigating molecular and cellular aspects of myelodysplasia utilising the NUP98-HOXD13 mouse model. One of these was the study of the role of apoptosis in transformation of myelodysplasia to acute leukaemia. In May 2013 he moved to the Department of Biochemistry and Molecular Biology at Monash University, to work on the basic science behind the promising leukemia therapeutic antibody KB004. From 2016, Dr Slape is a research leader at the University of Queensland Diamantina Institute.

Dr Slape's research career has had two primary objectives: to understand the mechanisms of transformation of chronic pre-leukemia conditions to acute leukemia, and to investigate the disease stem cells in pre-leukemia conditions to find therapeutic targets for both phases of haematological disease. The NUP98-HOXD13 transgenic mouse is an ideal model toward both ends; the mice have symptoms of MDS from birth, but only progress to acute myeloid leukemia (AML) after six months, and are therefore an ideal model to study the molecular events necessary to drive transformation from chronic to acute disease, or to study aberrantly self-renewing stem cells in isolation, prior to transformation.

Towards the first objective, Dr Slape has performed and published studies identifying spontaneous drivers of this transformation to disease, and also artificially driving transformation using a retroviral mutagenesis screen to identify induced oncogenic gene expression events. His apoptosis work has resulted in the paradigm-shifting discovery that apoptosis drives transformation of the disease to acute leukemia, where it has hitherto been thought of as a protective mechanism against cancer. Aspects of the second objective run throughout work directed at the first, but have come to the fore in his current work targeting disease stem cell interactions with their modified environment, and the role this plays in promoting their self-renewal. The current work aims to disrupt these interactions to evict the stem cells from the niche, assisting existing therapies to eradicate disease.