Molecular/cell biologist specialising in novel therapies for the treatment of haematological malignancies, principally childhood acute lymphoblastic leukaemia.
While the improvement in the treatment of childhood acute lymphoblastic leukaemia (ALL) over the last fifty years has been a resounding success, clinical challenges remain. They include the need for alternative therapies for relapsed disease and those at high risk of relapse due to persistent disease. In addition, treatment is prolonged, is associated with short and long term toxicity issues and some children may be cured with lesser treatment. The long term clinical goal may be to replace one or more of the standard therapeutic agents with a targeted, less toxic drug.
I lead a research team which aims to address these challenges by using advanced technologies to optimise therapy in children with ALL. We perform minimal residual disease quantitation by state of the art flow cytometry which is fundamental for stratifying treatment but importantly are leaders in the field in terms of qualitative analyses of these persisting cells. We have made significant advances in understanding the underlying drug resistant phenotype of these persisting cells and how it may be therapeutically exploited. Thus future treatment protocols may include novel drugs which target these residual cells in children with high levels of persisting disease and consequently at high risk of relapse. In terms of novel therapies for relapsed ALL, my group has shown that mutation of genes activating the RAS/RAF/MEK/ERK pathway is the most common genetic abnormality and have identified MEK inhibitors as a potential novel therapeutic option which would be applicable to around 40% of children. Therefore, we are currently performing preclinical evaluation of the MEK inhibitor AZD6244, now in Phase II clinical trials for other cancers, for RAS-mutated relapsed ALL. In addition, to these preclinical l studies, my laboratory are investigating predictive biomarkers and performing pharmacodynamic assessments in a CRUK sponsored phase 1 clinical trial of an aurora kinase inhibitor in children with multiple relapsed/refractory ALL.
I lecture on :-
The Molecular Basis of Cancer
Genetic variation in common disease
Integrated Biomedical Sciences
Genetics of Common Disease
Cancer Biology and Therapy
Carcinogenesis and Anticancer Drugs