Investigating novel therapeutic targets in acute myeloid leukaemia

Acute myeloid leukaemia (AML) is the second most common leukaemia in children and adolescents and the leading cause of childhood leukemic mortality. With the current treatment, based on chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 65-75% of patients will achieve long-term survival, however too many children with AML will die from direct complications of the harsh treatment or relapse, whereas the survivors suffer unacceptably high rates of long-term morbidity resulting from chemotherapy exposure or sequelae of bone marrow transplantation. As a result, the identification of new targeted therapy and cell therapy to improve overall survival in these children remain an unmet clinical need and the goal of Dr Maria Teresa Esposito’s research team. Her team has recently discovered that high level of expression of the gene SET significantly correlate with worse overall survival in adult AML. Strikingly, silencing SET abrogated the clonogenic potential of AML cells carrying various cytogenetic abnormalities and decreased the expression of HOXA genes, which are part of a gene expression signature highly predictive of poor outcomes and relapse in paediatric AML. This PhD project will continue this research and will investigate SET as a dependency and therapeutic target in pedAML, by employing an integrated molecular approach encompassing RNA-seq, ChiP-seq and mouse modelling coupled with gene silencing technology. 

The successful applicant will be given training in all aspects of the project and will be encouraged to develop as a motivated and independent researcher embedded in the sections of Immunology and Oncology and benefitting from the knowledge, experience and the multidisciplinary focus of the supervisory team, including Dr Lisiane Meira, an expert of DNA damage and its impact in cancer and chronic diseases, and international collaborators.

Applicants should ideally hold an excellent honours science degree (e.g. 1^st class or international equivalent) and a master’s degree in Cancer Biology, Molecular Biology, Biochemistry, Biomedical science or related discipline. Evidence of having undertaken a research project in a prior setting is essential. Knowledge of cancer biology or experience with cell culture, biological assays, real-time PCR, flow cytometry or in vivo work will be an advantage. Applicants must be self-motivated, independent thinkers with a deep interest in research and a collaborative attitude; they must have excellent organisational and communication skills with a very high level of written and spoken English.

Open to candidates who pay UK/home rate fees. See UKCISA for further information.