Dr. med. Tianzuo ZhanProject Leader B08
Small molecule inhibitors of MEK1/2 are clinically used for the treatment of cancers with activating Ras pathway mutations. Recently, MEK inhibitors were found to induce Wnt signaling in colorectal cancer, which is mediated by a rapid loss of AXIN1. AXIN1 is a main regulatory element of the destruction complex and its protein levels determine the activity of the canonical Wnt pathway. In this project, we will investigate if MEK inhibitors induce post-translational modifications of AXIN1, focusing on changes in phosphorylation and ubiquitination. We will determine if rewiring of interaction partners of AXIN1 occurs upon MEK inhibition and identify genetic alterations that modify the kinetics of AXIN1 degradation upon targeting of the Ras pathway.
Cross-Talk between p53 and Wnt Signaling in Cancer
Biomolecules. 2022 Mar 15;12(3):453. doi: 10.3390/biom12030453. PMID: 35327645Learn more
Multi-omics integration identifies a selective vulnerability of colorectal cancer subtypes to YM155
MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer
Nat Commun. 2019 May 16;10(1):2197. doi: 10.1038/s41467-019-09898-0. PMID: 31097693Learn more
CRISPR/Cas9 for cancer research and therapy
Semin Cancer Biol. 2019 Apr;55:106-119. doi: 10.1016/j.semcancer.2018.04.001. Epub 2018 Apr 16. PMID: 29673923Learn more
Wnt signaling in cancer
Oncogene. 2017 Mar;36(11):1461-1473. doi: 10.1038/onc.2016.304. Epub 2016 Sep 12. PMID: 27617575Learn more
CRISPRlibrary designer (CLD): software for multispecies design of single guide RNA libraries.
Genome Biol. 2016 Mar 24;17:55. doi: 10.1186/s13059-016-0915-2. PMID: 27013184Learn more