The role of deubiquitinating enzyme USP7 in the pathogenesis and treatment of acute myeloid leukemia (B08)

• Subject Area: Pharmacology ; Hematology, Oncology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217328187

Ubiquitination is an important post-translational protein modification frequently deregulated in cancer that can be exploited therapeutically. After having functionally characterized the deubiquitinating enzyme (DUB) BRCC3 as tumor suppressor gene in AML, we will now investigate the role of USP7, which we found to be an essential DUB in AML cell lines, as potentially targetable oncogene. We will 1) determine the impact of USP7 inactivation in AML by CRISPR/Cas9 and inhibitors in vitro and in vivo; 2) evaluate whether USP7 overexpression promotes leukemia development and drug resistance; and 3) identify new USP7 substrates implicated in AML by combining quantitative proteomics and functional genetics.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1074: Experimental Models and Clinical Translation in Leukemia
• Applicant Institution: Universität Ulm
• Project Head: Professor Dr. Jan Krönke, since 12/2019