Laboratory for Experimental Oncology

Scientific results:

We have created a wide range of mouse and human cell lines with knockouts of genes regulating ferroptosis, as well as two new mouse lines with FSP1 (FSP1^tg) or GPX4 overexpression, which has expanded the list of already existing models and significantly extended the research opportunities in both in vitro and in vivo systems. The created genetically-modified cell and mouse lines can be used for the research of the potential of ferroptosis as a cancer therapy. For instance, using syngeneic mouse models, we conducted experiments to assess the contribution of proteins regulating ferroptosis on the process of tumor growth when transplanting cells of the breast cancer line. We have started working to determine the contribution of FSP1 to the development of hepatocellular carcinoma, models of induction of which by the hydrodynamic transfection of oncogenes or the introduction of diethylamine were refined on wild-type mice. In the domain of the pharmacological activation of ferroptosis to fight tumor growth and metastasis, we have started a research to select the most efficient FSP1 inhibitors. Moreover, within the problem of searching for new inducer of ferroptosis we have conducted experiments in the use of D-amino acid oxidase, DAAO, as a new spatiotemporal inducer of ferroptosis cascades. Some of the genes that are potential suppressors of ferroptosis, identified in a full-genome screening with the use of a lentivirus library, are currently at the testing stage.

We have created a wide range of mouse and human cell lines with knockouts of genes regulating ferroptosis, as well as two new mouse lines with FSP1 (FSP1^tg) or GPX4 overexpression, which has expanded the list of already existing models and significantly extended the research opportunities in both in vitro and in vivo systems. The created genetically-modified cell and mouse lines can be used for the research of the potential of ferroptosis as a cancer therapy. For instance, using syngeneic mouse models, we conducted experiments to assess the contribution of proteins regulating ferroptosis on the process of tumor growth when transplanting cells of the breast cancer line. We have started working to determine the contribution of FSP1 to the development of hepatocellular carcinoma, models of induction of which by the hydrodynamic transfection of oncogenes or the introduction of diethylamine were refined on wild-type mice. In the domain of the pharmacological activation of ferroptosis to fight tumor growth and metastasis, we have started a research to select the most efficient FSP1 inhibitors. Moreover, within the problem of searching for new inducer of ferroptosis we have conducted experiments in the use of D-amino acid oxidase, DAAO, as a new spatiotemporal inducer of ferroptosis cascades. Some of the genes that are potential suppressors of ferroptosis, identified in a full-genome screening with the use of a lentivirus library, are currently at the testing stage.

Implementation of research results:

We have produced and characterized two transgenic mouse lines on the basis of C57Bl/6J with an induced overexpression of FSP1 (FSP1^tg) or GPX4. These animals are used for the assessment of the therapeutic potential of the ferroptosis-regulating proteins FSP1 and GPX4 in various models of oncogenesis.

Education and retraining of personnel:

• In 2021, on the basis of Pirogov Russian National Research Medical University we conducted the conference «Ferroptosis in Health and Disease».
• One Candidate of Sciences dissertation has been prepared and defended.
• Four employees of the Laboratory have completed internships at the leading scientist’s place of work.