Investigating the role of SET/PP2A in haematopoietic and leukemic stem cells

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. For elderly AML patients, the chances of survival are even worse (13.6%).

As a result, identifying new targeted therapy and cell therapy to improve overall survival in these patients 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 AML. This PhD project will continue this research and will explore the role of SET in haematopoietic and leukemic stem cells, by employing an integrated molecular approach and animal models.

The successful applicant will be highly self-motivated, possessing the organizational skills, resilience and drive necessary to manage an independent research project and produce high-quality impactful academic research. The PhD student will be embedded in the sections of Immunology and Oncology and will benefit 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 external collaborators.

This studentship is open to candidates who pay UK/home rate fees.

Applicants should ideally hold an excellent honours science degree (e.g. First class or international equivalent) and a masters 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, cloning, flow cytometry or in vivo work will be an advantage.

The successful applicant will be highly self-motivated, possessing the organizational skills, resilience and drive necessary to manage an independent research project and produce high-quality impactful academic research; they must have excellent communication skills with a very high level of written and spoken English.