Skip to main content
European Commission logo
English English
CORDIS - EU research results
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary
Content archived on 2024-05-27

Small Molecule Antagonists of chromatin modifying enzymes for Regulation of Transcription, proliferation and differentiation

Final Report Summary - SMART (Small Molecule Antagonists of chromatin modifying enzymes for Regulation of Transcription, proliferation and differentiation)

Executive summary

The project aimed at the generation of small molecular probes targeting histone-modifying enzymes and using them, together with functional genomics, to study the role of chromatin in cellular proliferation and differentiation. These goals were pursued in model systems for transdifferentiation towards insulin producing beta cells and for proliferation control of cancer cells. The project was carried out at the Broad Institute of Harvard and the Massachusetts Institute of Technology (MIT) (Boston, United States of America, advisor Stuart Schreiber) and CeMM (Vienna, Austria, advisor Giulio Superti-Furga).

The key achievements during the project were:

- four primary research articles;
- presentation of work at eight conferences and lectures;
- two years at the Broad Institute of Harvard and MIT followed by one year of knowledge transfer for the establishment of the CeMM screening platform;
- high-throughput screening for histone demethylase inhibitors and the development of methylstat as the first specific demethylase inhibitor;
- identification and characterisation of BRD7389 as a small molecular inducer of insulin secretion in pancreatic beta cells;
- characterisation of 44 chromatin-targeted compounds for their effects on gene expression in pancreatic alpha and beta cells.
In summary, this Marie Curie International Outgoing Fellowship project has not only been successful scientifically, but has also enabled the knowledge transfer from a premier United States research institute to Europe, and provided a path to scientific independence for the research fellow.