Stefan Kubicek

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 work in close connection to cellular metabolism to regulate gene expression. Using innovative approaches in cell biology and chemical biology, we identify and validate metabolic activities in the cell’s nucleus as therapeutic targets in cancer and diabetes, and develop novel chemical probes against these key 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. Their direct link to transcriptional regulation makes chromatin-modifying enzymes a prime synthetic lethal target in many genetically defined cancer types. We systematically study chromatin-modifying proteins and the metabolic pathways that provide cofactors for chromatin modification in cancer development and progression, with a particular focus on ATP-dependent chromatin remodeling processes.

At the same time, we develop innovative phenotypic assays to systematically identify and optimize small molecules that alter the abundance or subcellular localization of nuclear proteins. These compounds serve as chemical biology tools to investigate protein function and could be the starting point for epigenetics-based drug discovery.
 

Cellular transdifferentiation in the endocrine pancreas 

Epigenetic modifications play crucial roles in cell type specification, and small molecule inhibitors of chromatin-modifying enzymes have been shown to enhance the efficiency of cellular reprogramming. We hypothesize that targeting chromatin remodeling can support the generation of therapeutically relevant cell types for regenerative medicine by promoting cellular transdifferentiation.

Our research focuses on the endocrine pancreas, particularly on developmentally related cell types from the islets of Langerhans. We use functional genomics and chemical biology probes to explore epigenetic plasticity between these cell types. Our goal is to reprogram other cell types into insulin-producing pancreatic beta-like cells, offering a potential alternative treatment for diabetes through cell-based therapy.

Stefan Kubicek joined CeMM in 2010. He obtained an MSc in Synthetic Organic Chemistry from the Vienna University of Technology after writing a diploma thesis at ETH Zurich. For his PhD in Thomas Jenuwein’s lab at the IMP in Vienna, he changed fields to molecular biology and developed the first selective histone methyl transferase inhibitors. He then performed postdoctoral research, working on chemical biology with Stuart Schreiber at the Broad Institute of Harvard and MIT. At CeMM, Stefan Kubicek headed the Christian Doppler Laboratory for Chemical Epigenetics and Antiinfectives, a public-private partnership between CeMM, Boehringer Ingelheim, and Haplogen, and is now the head of the CeMM Molecular Discovery Platform. The Kubicek lab studies chromatin, epigenetics and small molecules that change cell fates in oncology and diabetes with a particular focus on metabolism in the cell’s nucleus.