A novel role for (de)ubiquitinating enzymes in the MAPK and TGFB pathways

Protein modification by ubiquitination has emerged as a critical regulatory event in virtually all aspects of cell biology. Ubiquitination is a reversible process, and ubiquitin moieties can be removed from polypeptides by deubiquitinating enzymes (DUBs). Using a shRNA deubiquitinating enzyme library we have sought to understand the role of deubiquitinating enzymes in cancer progression with the goal to identify novel mechanistic biomarkers that predict response to targeted therapies presently being used in the clinic. This presentation will show some of our most recent findings including our work on the identification of a number of deubiquitinating enyzmes involved in vemurafenib resistance in BRAF mutant melanoma. In addition, we have identified the deubiquitinating enzymes USP15 and USP26 as novel modulators of the TGF-beta pathway and critical factors in glioblastoma pathogeneisis. I will provide a brief summary on both of these stories and the present work that we are doing in my lab.


Dr. Pieter Eichhorn is a group leader at the Cancer Science Institute of Singapore. He holds a bachelor of science degree specializing in human genetics from the University of Western Ontario. He did his Ph.D. work under the direction of Prof. Tom Strachan at the University of Newcastle upon Tyne, focusing on cloning of the gene for Cornelia de Lange syndrome. He then did his postgraduate studies with Rene Bernards at the Netherlands Cancer Institute, Amsterdam, where he performed some of the first RNAi screens in mammalian cells that led to the identification of the PP2A subunit PR55 gamma as a potent inhibitor of the oncogene c-SRC. In 2006 he joined the lab of Jose Baselga at Vall d’Hebron Institute of Oncology, Barcelona, where he continued utilizing genome wide technologies to identify novel genes in cancer relevant pathways, including work that led to the identification of PI3K hyperactivation in Lapatinib resistance. In 2010 he became a faculty member at Massachusetts General Hospital and Harvard Medical School where he identified both cyclin E and RSK4 as mechanisms of resistance to Trastuzumab and PI3K inhibitors, respectively. Since joining the Cancer Science Institute, Pieter’s research is mostly focused on the role deubiquitinating enzymes in the TGFβ pathway and the identification of factors involved in targeted therapeutic resistance.