PROJECT SUMMARY

RUNX1 is a transcription factor, which is a class of proteins that control what genes are turned on or off in a cell. RUNX1 is also recurrently mutated in MDS. The goal of this project is to determine what genes RUNX1 controls, how it controls them, and how RUNX1 mutations observed in MDS change the way RUNX1 works. We hope that if we understand what RUNX1 normally does, we’ll be able to understand how things go wrong when it is mutated, and how this leads to the development of MDS. In the past, it has been hard to study what RUNX1 normally does, because old technology took a long time (days to weeks) to get rid of RUNX1. Lots of things can change in days to weeks, and not all of them are directly related to RUNX1. We now have a way to get rid of RUNX1 in 1-2 hours, which will allow us to define the direct functions of RUNX1, and how RUNX1 mutations affect its activity. Understanding how RUNX1 activity is altered in MDS will be key to identifying new targeted therapies to treat RUNX1-mutant MDS and/or better stratify patients to inform therapeutic decision making.