Dr. Andrei Gartel
I have an extensive knowledge in molecular and cellular biology, and in identification of potential anticancer drugs. I am an academic editor of PLOS One and a reviewer for many different grant agencies, including NIH, Medical Research Council (United Kingdom) and the Welcome Trust (United Kingdom). Earlier, my major contribution to the field was a discovery that c-Myc negatively regulates transcription of the CDK inhibitor p21 via interaction with transcription factors Sp1/Sp3 (376 citations). In addition, my laboratory discovered the presence of alternate p21 transcripts that are strongly regulated by p53 in human and mouse cells. When my laboratory was looking for pro-apoptotic compounds that inhibit p21, we discovered nucleoside analog ARC (NSC-188491) that acts as a transcriptional inhibitor. We found positive auto-regulation loop of the oncogenic transcription factor FOXM1 and negative regulation of FOXM1 by tumor suppressor p53. Recently, my laboratory demonstrated that the thiazole antibiotics, thiostrepton and Siomycin A, but not other thiazole antibiotics inhibit FOXM1 and act as proteasome inhibitors. Moreover, we found that well-known proteasome inhibitors such as bortezomib and MG132 also inhibit FOXM1 expression. We also found that in cancer cells nucleophosmin (NPM) interacts with FOXM1 and their interaction is required for sustaining the level and localization of FOXM1. Moreover, we determined that mutant NPM in that was localized in the cytoplasm of the leukemia cells led to re-localization of FOXM1 to the same compartment. We showed that cytoplasmic localization and inactivation of oncogenic transcription factor FOXM1 in AML correlates with improved outcome of the disease, suggesting that nuclear FOXM1 is an oncogene in AML. Recently we discovered drugs that target the interaction between FOXM1 and NPM and destabilize FOXM1 expression. These compounds may represent in a novel therapeutic strategy against human cancer.