The Kubicek Laboratory works in the field of Chemical Epigenetics, aiming to discover, develop and characterize small molecules that impact cellular identity. Cell type and cell fate decisions are controlled by chromatin pathways that regulate transcription. Using innovative cell and chemical biological approaches, we identify and validate chromatin-modifying enzymes as therapeutic targets in cancer and diabetes, and develop novel chemical probes against these epigenetic factors. 

Chromatin pathways in cancer

Chromatin aberrations play causative roles in leukemia and solid tumors, where epigenetic modifiers are often aberrantly expressed or genetically altered. At the same time, their direct link to transcriptional control makes chromatin-modifying enzymes a prime synthetic lethal target in many additional genetically defined cancers. Our goal is to systematically study the role of the approximately 400 chromatin modifying proteins in cancer development and progression, and identify key players as potentially druggable targets.

At the same time, we develop innovative phenotypic assays to identify and optimize small molecules that inhibit the epigenetic writers, readers and erasers. Such compounds will be used as chemical probes to study the function of these proteins, and could also for a starting point for further development of new anti-cancer drugs.

Cellular transdifferentiation in the endocrine pancreas 

Epigenetic modifications play important roles in cell type specification, and small molecule inhibitors of several chromatin modifying enzymes have been shown to increase the efficiency of cellular reprogramming. We hypothesize that targeting chromatin can contribute to the formation of therapeutically relevant cell types for regenerative medicine by promoting cellular transdifferentiation. 

We focus on the endocrine pancreas, where several developmentally closely related cell types from the insets of Langerhans. We use functional genomics and chemical biology probes to understand epigenetic plasticity between these cell types. Our goal is to convert other cell types to insulin-producing pancreatic beta-like cells, which could be used to develop an alternative approach for treating diabetes.


Stefan Kubicek studied organic chemistry in Vienna and Zürich. He received his Ph.D. in Thomas Jenuwein’s group at the IMP in Vienna followed by postdoctoral work with Stuart Schreiber at the Broad Institute of Harvard and MIT in the U.S. He joined CeMM in 2010.

Selected Papers

Licciardello, M. P. et al. A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor. Nat Chem Biol (2017). (abstract)

Li, J. et al. Artemisinins Target GABAA Receptor Signaling and Impair alpha Cell Identity. Cell 168, 86-100 (2017). (abstract)

Sdelci, S. et al. Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk. Nat Chem Biol 12, 504-510 (2016). (abstract)

Li, J. et al. Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types. EMBO Rep 17, 178-187 (2016). (abstract)

Licciardello, M. P. et al. NOTCH1 activation in breast cancer confers sensitivity to inhibition of SUMOylation. Oncogene 34, 3780-3790 (2015). (abstract)

Mair, B., Kubicek, S. & Nijman, S. M. Exploiting epigenetic vulnerabilities for cancer therapeutics. Trends Pharmacol Sci 35, 136-145 (2014). (abstract)

Kubicek, S. et al. Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells. Proc Natl Acad Sci U S A 109, 5364-5369 (2012). (abstract)

Fomina-Yadlin, D. et al. Small-molecule inducers of insulin expression in pancreatic alpha-cells. Proc Natl Acad Sci U S A 107, 15099-15104 (2010). (abstract)

Kubicek, S. et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25, 473-481 (2007). (abstract)