My aim is to broaden our understanding of the pathogenesis of haematopoietic malignancies with a focus on acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL), and to exploit this knowledge for the development of new cancer therapies.
Within the Adams Group, I am currently working with Dr Chi Wong to identify the consequences of combinatorial gene knockouts on normal and malignant haematopoiesis in in vivo mouse models. In a second project, I am performing a series of in vitro experiments to functionally validate recurrent mutations as therapeutic targets in CLL.
During my PhD studies I worked on the identification and characterisation of the receptor tyrosine kinase RET, which is commonly mutated in solid tumours, as an essential, albeit structurally intact kinase in AML. As published in Leukemia, my colleagues and I linked increased RET expression and signalling to reduced levels of autophagy, which result in the stabilisation of leukaemogenic drivers such as mutant FLT3. Importantly, targeting RET may represent a novel strategy in AML therapy, as we demonstrated that genetic or pharmacologic RET inhibition promotes FLT3 degradation through induction of autophagy and impairs cell viability of AML subtypes dependent on mutant FLT3 and possibly other leukaemogenic drivers that are also regulated by autophagy.
Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma.
JAMA dermatology 2018
RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia.