A research group at Helmholtz Zentrum München, Neuherberg, Germany.
Biomedical research for redox-regulated life and death decisions.
Ferroptosis in degenerative disease and cancer.
Primer article on ferroptosis published in Cell
Along with a number of researchers active in the field of ferroptosis, a Primer article was recently published in Cell. This article provides a state-of-the-art overview on the different facets of the molecular underpinnings of the ferroptotic process and sets guidelines for future studies when exploring this novel, non-apoptotic cell death modality (Further reading: Stockwell et al. (2017) Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell 171:273-285).
ACSL4 predicts sensitivity to ferroptosis in a subset of triple negative breast cancer cells
In search of novel ferroptosis players the Conrad laboratory has recently applied CRISPR/Cas9-based, genome-wide genetic screens along with cellular and pharmacological approaches leading to the identification and validation of acyl-CoA synthetase long-chain family member 4 (ACSL4) as an important determinant in the ferroptotic process (Doll et al., Nat Chem Biol 2017). By shaping the cellular lipidome ACSL4 is involved in the generation of the so-called lipid death signal of ferroptosis (Kagan et al., Nat Chem Biol 2017) (see also "How cells die by ferroptosis").
The relevance of selenium utilization by the ferroptosis regulator GPX4 unveiled
Our recent work published in Cell demonstrates that the trace element selenium, discovered 200 years ago by a Swedish scientist, in form of the 21st amino acid selenocysteine was an evolutionary requirement to prevent peroxide-induced inactivation of the ferroptosis regulator glutathione peroxidase 4 (GPX4) (Ingold et al., 2018). Selenium-containing GPX4 thus allows the exploitation of a rich set of polyunsaturated fatty acids in cellular membranes for the development of complex neuronal circuits in mammals and other vertebrates, and the utilization of physiological concentrations of peroxides for redox signaling processes in cells (see also " Selenium protects a specific type of interneurons in the brain").
About Dr. Conrad
The Conrad laboratory investigates the molecular underpinnings about life and death decisions made by cells in normal tissue homeostasis and in disease. While early cell loss and tissue dysfunction causes acute and chronic degenerative diseases such as ischemia/reperfusion injury and neurodegeneration, aberrant killing of premalignant cells is a known factor in tumor development. The main research focus of the Conrad laboratory involves how perturbed cell metabolism, aberrant redox homeostasis and endoplasmic reticulum stress impact on cell death.Learn more