The laboratory was created within the framework of the program of international cooperation between Russian universities and scientific organizations with world-class scientists and leading foreign scientific and educational centers in the fields of science, education and innovation "Megagrants".
General Information
Recent findings revealed that “therapy-persister” and mesenchymal cancer cells emerge to be highly sensitive to ferroptosis, a quite recently described form of regulated non-apoptotic cell death modality marked by iron-dependent lipid peroxidation. Current studies of our laboratory are focused on investigating the molecular mechanisms of ferroptosis in the context of tumorigenesis, particularly in the sensitization and execution of ferroptosis in different cancer models. Our studies aim to provide novel data for the development of new ferroptosis-inducing therapeutics to combat difficult-to-treat and metastatic tumors.
Goals and objectives:
Expected results:
Molecular components of the ferroptosis cascade, including its activators and inhibitors, and mechanisms of ferroptosis regulation will be identified and characterized. Data on the efficacy of low molecular synthetic ferroptosis inducers to prevent the growth and spread of different tumors will also be provided. Results obtained herein will thus expand our knowledge on the implementation of ferroptosis induction as a novel anticancer strategy.
Dr. Marcus Conrad and his colleagues generated the first mouse models with conditional knockout of the main mammalian redox-enzymes, such as cytosolic and mitochondrial thioredoxin reductases TXNRD1 and TXNRD2, respectively, as well as glutathione peroxidase 4 (GPX4). Actually, long before the term ferroptosis was coined, Dr. Conrad provided first evidence that deletion of the key ferroptosis regulator GPX4 causes a previously uncharacterized cell death modality, now known as ferroptosis. His laboratory also developed the first in vivo efficacious synthetic ferroptosis inhibitors, called liproxstatins. In one of his recent reports, the role of selenocysteine in the prevention of the active site of GPX4 from overoxidation and consequently from initiation of ferroptosis has been elaborated. In addition, new regulators of ferroptosis, i.e. ASCL4 (acyl-CoA synthetase long chain family member 4) and FSP1 (ferroptosis suppressor protein 1), have recently been identified by the Dr. Conrad laboratory using whole genome screening approaches.
