Chemical Biology and Epigenetics
Identification and development of small molecule probes for biological processes
Contribution of histone lysine methylation to cancer development and progression
Chemical probe compounds targeting histone lysine methylation pathways (histone methyltransferases, demethylases, methyl-binding domain proteins)
Role of chromatin in the specification of pancreatic cell types
Targeting chromatin modifying enzymes for the generation of beta-like insulin producing cells from other cell types
The Kubicek lab is working on the role of chromatin in the definition of cell types and cell states. Projects focus on defining the contribution of histone methylation to cancer development and progression and targeting these processes with small molecules. Furthermore, we are interested in targeting epigenetic marks for cellular transdifferentiation, with the goal of generating insulin-producing beta cells from other cell types.
Cell biology, protein biochemistry, proteomics, functional genomics, high-throughput screening, chemical proteomics
Stefan Kubicek, Josh Gilbert, Dina Fomina-Yadlin, Alex Gitlin, Yuan Yuan Florence Wagner, Ed Holson, Tuoping Luo, Tim Lewis, Brad Taylor, Supriya Gupta, Alykhan Shamji, Bridget K. Wagner, Paul A. Clemons, and Stuart L. Schreiber (2012). Compounds targeting chromatin modifying enzyme induce specific cell-type independent transcription signatures in the endocrine pancreas. PNAS 109, 5364-5369.
Dina Fomina*, Stefan Kubicek*, Depeeka Walpita, Vlado Dancik, Jacob Hecksher-Sørensen , Joshua Bittker, Tanaz Sharifnia, Alykhan Shamji, Paul A. Clemons, Bridget K. Wagner, and Stuart L. Schreiber (2010). Small molecule inducers of insulin expression in pancreatic alpha cells. PNAS 107, 15099-15104.
Stefan Kubicek, Roderick J. O’Sullivan, E. Michael August, Eugene R. Hickey, Qiang Zhang, Miguel L. Teodoro, Karl Mechtler, Stephen Rea, Jennifer A. Kowalski, Carol Ann Homon, Terence A. Kelly, and Thomas Jenuwein (2007). Transient reversal of H3K9me2 by a small molecule inhibitor for the G9a histone methyltransferase. Mol. Cell 25, 473-481.
Barna D. Fodor*, Stefan Kubicek*, Masato Yonezawa, Roderick J. O’Sullivan, Roopsha Sengupta, Laura Perez-Burgos, Susanne Opravil, Karl Mechtler, Gunnar Schotta, and Thomas Jenuwein (2006). Jmjd2b antagonizes H3K9 tri-methylation at pericentric heterochromatin in mammalian cells. Genes Dev. 20, 1557-1562.
Stefan Kubicek and Thomas Jenuwein (2004). A Crack in Histone Lysine Methylation. Cell 119, 903-906.