Exploring MLLT therapeutics in haematology
Summary
A major challenge in cancer therapeutics has been the identification of targets that are selectively toxic to cancer cells while displaying limited effects on healthy counterparts. This project will focus on novel drugs targeting the transcriptional complex called the Super Elongation Complex (SEC).
SEC has been identified as an exciting potential therapeutic target in several blood cancers, including paediatric acute leukaemias (Rajhansa et al., bioRxiv 2024). MLLT proteins are epigenetic readers within the SEC that are attractive drug targets. Beyond their role in cancer, MLLT proteins have also been shown to regulate normal haematopoietic stem cell self-renewal during fetal development. However, MLLT proteins have not been explored in post-natal or adult human HSCs and there remain important unanswered questions related to their role and requirement in these contexts.
Project aims
The main aims of this project are to:
- assess the activity of compounds targeting MLLT in adult human HSCs,
- determine the consequences of targeting MLLT and other SEC components on human HSC function ex vivo and in vivo, and
- investigate the molecular role of MLLT proteins and other SEC components in HSCs.
The project will leverage novel compounds generated by Dark Blue Therapeutics and powerful ex vivo HSC culture technologies available in the Wilkinson group (Wilkinson et al., Nature 2019; Sakurai et al., Nature 2023), alongside a range of functional and transcriptional assays.
Contact details
Adam Wilkinson - acw63@cam.ac.uk
Opportunities
This project is open to applicants who want to do a:
- PhD