ChemBio seminar by Prof. Marcus Conrad (Helmholtz Munich) - CH-635
Event details
| Date | 24.09.2024 |
| Hour | 16:15 › 17:15 |
| Speaker | Prof. Marcus Conrad |
| Location |
TBC
|
| Category | Conferences - Seminars |
| Event Language | English |
Title: Ferroptosis as the underlying mechanism in neurodegenerative disease?
Abstract:
Selenium-dependent glutathione peroxidase 4 (GPX4), formerly known as phospholipid hydroperoxide glutathione peroxidase (PHGPx), is the guardian of ferroptosis due to its unique role in reducing peroxides in phospholipid bilayers to their corresponding alcohols. While genetic deletion of Gpx4 in mice leads to early embryonic death at the gastrulation stage, the occurrence of biallelic deleterious variants of GPX4 is associated with the ultra-rare congenital disorder Sedaghatian-type spondylometaphyseal dysplasia (SSMD). SSMD is a disease that is usually fatal within a few days of birth and is characterised by severe chondrodysplasia, delayed epiphyseal ossification, irregular iliac crests, severe hypotonia and cardiorespiratory problems. In addition, affected patients exhibit severe central nervous system defects that include mental, behavioural and motor deficits. To investigate the molecular and structural basis of GPX4 in ferroptosis and neuroprotection, we have extensively studied a missense variant recently identified in SSMD patients. These studies not only elucidated the structural basis of GPX4 for ferroptosis prevention, but also uncovered the cell death process underlying neurodegeneration in humans. Our findings should therefore guide future efforts to develop ferroptosis-based therapies for the treatment of neurodegenerative diseases and beyond.
Speaker's biography:
Marcus Conrad is Director of the Institute of Metabolism and Cell Death at Helmholtz Zentrum München. Marcus Conrad studied biology at the University of Konstanz, Germany, and received his doctorate with distinction from Ludwig-Maximilians-University Munich in 2001. After a short postdoctoral period, he was an independent group leader until 2009 at Helmholtz Zentrum München. From 2009 – 2010 he was employed as Laboratory Head at Bayer-Schering AG, Berlin. After two years at the newly founded German Center for Neurodegenerative Diseases, he returned to Helmholtz Zentrum München as research group leader in 2012. In 2020, he was appointed Director of the Institute of Metabolism and Cell Death. His laboratory has pioneered the field of ferroptosis and made a number of groundbreaking contributions to our understanding of oxidative cell death both in (neuro)degenerative diseases and cancer. He discovered the first in vivo active ferroptosis inhibitors, the so-called liproxstatins, whose next generation variants have already entered preclinical development to be used for the treatment of (neuro)degenerative disease. Marcus Conrad has published more than 160 articles, holds several patents and is co-founder and shareholder of ROSCUE Therapeutics GmbH. He was recently appointed as a new member of the Hinterzarten Circle of the Deutsche Forschungsgemeinschaft (DFG) on cancer research.
Lab website: https://www.conradlaboratory.com/
Abstract:
Selenium-dependent glutathione peroxidase 4 (GPX4), formerly known as phospholipid hydroperoxide glutathione peroxidase (PHGPx), is the guardian of ferroptosis due to its unique role in reducing peroxides in phospholipid bilayers to their corresponding alcohols. While genetic deletion of Gpx4 in mice leads to early embryonic death at the gastrulation stage, the occurrence of biallelic deleterious variants of GPX4 is associated with the ultra-rare congenital disorder Sedaghatian-type spondylometaphyseal dysplasia (SSMD). SSMD is a disease that is usually fatal within a few days of birth and is characterised by severe chondrodysplasia, delayed epiphyseal ossification, irregular iliac crests, severe hypotonia and cardiorespiratory problems. In addition, affected patients exhibit severe central nervous system defects that include mental, behavioural and motor deficits. To investigate the molecular and structural basis of GPX4 in ferroptosis and neuroprotection, we have extensively studied a missense variant recently identified in SSMD patients. These studies not only elucidated the structural basis of GPX4 for ferroptosis prevention, but also uncovered the cell death process underlying neurodegeneration in humans. Our findings should therefore guide future efforts to develop ferroptosis-based therapies for the treatment of neurodegenerative diseases and beyond.
Speaker's biography:
Marcus Conrad is Director of the Institute of Metabolism and Cell Death at Helmholtz Zentrum München. Marcus Conrad studied biology at the University of Konstanz, Germany, and received his doctorate with distinction from Ludwig-Maximilians-University Munich in 2001. After a short postdoctoral period, he was an independent group leader until 2009 at Helmholtz Zentrum München. From 2009 – 2010 he was employed as Laboratory Head at Bayer-Schering AG, Berlin. After two years at the newly founded German Center for Neurodegenerative Diseases, he returned to Helmholtz Zentrum München as research group leader in 2012. In 2020, he was appointed Director of the Institute of Metabolism and Cell Death. His laboratory has pioneered the field of ferroptosis and made a number of groundbreaking contributions to our understanding of oxidative cell death both in (neuro)degenerative diseases and cancer. He discovered the first in vivo active ferroptosis inhibitors, the so-called liproxstatins, whose next generation variants have already entered preclinical development to be used for the treatment of (neuro)degenerative disease. Marcus Conrad has published more than 160 articles, holds several patents and is co-founder and shareholder of ROSCUE Therapeutics GmbH. He was recently appointed as a new member of the Hinterzarten Circle of the Deutsche Forschungsgemeinschaft (DFG) on cancer research.
Lab website: https://www.conradlaboratory.com/
Practical information
- Informed public
- Free