Molecular Determinants of Secondary AML: Mechanisms and Vulnerabilities in Leukemic Transformation University of Oxford in United Kingdom

This funded PhD project at the University of Oxford investigates the molecular determinants of secondary acute myeloid leukemia (sAML), a devastating blood cancer arising from pre-leukemic disorders such as myeloproliferative neoplasms (MPNs) and myelodysplasia. With a median survival of only five months and limited therapeutic options, sAML represents a critical challenge in clinical medicine and cancer biology.

The research aims to uncover how altered transcription factors and chromatin proteins redistribute to drive leukemic gene expression and to understand why current therapies fail. By elucidating the mechanisms of transformation, the project seeks to expose new vulnerabilities and predict disease progression, ultimately contributing to improved intervention strategies.

Students will analyze gene expression and DNA methylation data from sAML patients, integrating these with cell and animal models engineered to carry sAML-related driver gene mutations. The project employs advanced genomic techniques, including whole genome DNA methylation profiling, gene expression analysis, chromatin accessibility assays, and transcription factor occupancy mapping, to investigate disrupted transcriptional networks and chromatin alterations. The observational phase will be followed by hypothesis generation and wet-lab experiments, such as Cut&Run occupancy and chromatin conformation assays, to validate findings and explore functional consequences.

The position is based in the Nuffield Department of Medicine and is supervised by Professors S Kriaucionis and S Constantinescu, both leading experts in cancer genomics and molecular biology. The Ludwig studentship provides four years of funding, including a tax-free stipend (£23,000 per annum) and coverage of university fees for both home and international students.

Applicants must apply through the University of Oxford application system for a DPhil in Clinical Medicine, using course code 'RD_CM1'. A personal statement is required, and candidates may apply for up to two Ludwig projects. It is recommended to contact the supervisor to discuss your application and suitability for the lab. No research proposal is needed, but referees must be prepared to submit references by the deadline. The application deadline is April 9, 2026.

For project enquiries, contact Prof S Kriaucionis at [email protected]. For administrative questions, email [email protected]. Further details and application instructions are available on the University of Oxford Graduate Admissions website.