Oncogene addiction and targeted therapeutic development
in MYC-driven B-cell lymphoma
A major research focus in the group is to unravel the molecular mechanisms underlying the oncogenic action of the MYC transcription factor (1-3) and exploit them for pre-clinical development of targeted therapies (4, 5). For example, our work revealed mitochondrial translation and respiratory activity as effective therapeutic targets in aggressive MYC-driven lymphomas: drugs that suppress these molecular processes show synthetic lethality with MYC activation in B-cells and strong anti-tumoral activity against B-cell lymphoma xenografts, especially when combined with BH3-mimetic compounds targeting select BCL2-family members (6-9). Through a combination of mechanism-driven hypotheses and high-throughput screens, we recently identified new molecular targets and compounds with equally promising potential against MYC-driven malignancies.
We seek to recruit an ambitious, motivated, team-oriented scientist with a PhD in life sciences. The successful candidate will address the therapeutic potential and mechanisms of action of select genes and drugs in MYC-associated lymphomas. The project will combine cell- and xenograft-based models with state-of-the-art molecular and genomic technologies, and will benefit from a highly integrated, multidisciplinary and supportive research environment. Prior experience in cellular, molecular and/or mouse biology will be an asset, but other specialty areas will also be positively considered. Spoken and written communication skills in English are required.
Applications will be received until assignment of the position, available from January 31, 2023.
- A. Sabò, B. Amati, Genome recognition by MYC. Cold Spring Harb Perspect Med 4, a014191 (2014). doi:10.1101/cshperspect.a014191.
- T. R. Kress, A. Sabò, B. Amati, MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer 15, 593-607 (2015). doi:10.1038/nrc3984.
- A. Sabò, B. Amati, BRD4 and MYC-clarifying regulatory specificity. Science 360, 713-714 (2018). doi:10.1126/science.aat6664.
- A. Bisso, A. Sabò, B. Amati, MYC in Germinal Center-derived lymphomas: Mechanisms and therapeutic opportunities. Immunol Rev 288, 178-197 (2019). doi:10.1111/imr.12734.
- G. Donati, B. Amati, MYC and therapy resistance in cancer: risks and opportunities. Mol Oncol 16, 3828-3854 (2022). doi:10.1002/1878-0261.13319.
- A. D'Andrea et al., The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas. Oncotarget 7, 72415-72430 (2016). doi:10.18632/oncotarget.11719.
- M. Ravà et al., Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma. Sci Transl Med 10, eaan8723 (2018). doi:10.1126/scitranslmed.aan8723.
- G. Donati et al., Targeting mitochondrial respiration and the BCL2 family in high-grade MYC-associated B-cell lymphoma. Mol Oncol 16, 1132-1152 (2022). doi:10.1002/1878- 0261.13115.
- G. Donati et al., Oxidative stress potentiates the therapeutic action of a mitochondrial complex I inhibitor in MYC-driven B- cell lymphoma. bioRxiv, 2022.2006.2021.497021 (2022). doi:10.1101/2022.06.21.497021.