1. Cellular sulfur chemistry and its diverse roles in redox biology

Sulfur is the atom that living systems usually use to modulate the oxidation status of oxygen. Prof. P. Nagy of the RBL has devoted much of his career to understanding the intricate ways cells and enzymes use sulfur in diverse reactions.  A current focus is on the biological activities of sulfide, persulfides, and polysulfides in homeostasis, signaling, and stress responses. Prof. E. Schmidt has been focusing on how altered metabolism of sulfur amino acids can provide added support for sustaining redox homeostasis in cells under oxidative stress.

2. Genetically modified mouse models for studying redox biology

Animal models, in particular genetically modified mouse (GEM) models, provide unparalleled systems for understanding the genetic basis of redox activities in the context of normal or disease physiology.  Prof E. Schmidt from the RBL has developed some of the world’s most important mouse models with loss-, gain-, or change-of-function mutations in redox systems. Current activities integrate CRISPR-mediated somatic cell complementation assays with classic germline GEM models to probe the intricate mechanisms of redox systems.

3. Redox signaling

The importance of redox regulation of signaling events is becoming widely appreciated, with recognition of the roles of regulated H₂O₂ production in modulating the oxidation status of regulatory cysteine residues in many proteins.  Even more importantly, there is increasing recognition of the roles of highly efficient H₂O₂-driven oxidation catalysts, in particular the peroxiredoxin enzymes, or of highly specialized context-dependent “peroxidatic” cysteine residues on target enzymes, which catalytically surmount critical kinetic barriers to cysteine oxidation.  Other redox regulatory modifications, including S-nitrosylation and S-persulfidation are also coming into the spotlight. Prof. P. Nagy from the RBL is a world renown leader in the field of cysteine modifications, cysteine reaction rate kinetics, and enzymes involved in these processes. Recent work has focused on persulfidation, and this work is at the forefront of activities at the RBL.

4. Redox in disease

Many diseases and disease processes, as well as many defense mechanisms against diseases, have redox components. Notable among these are cancers and inflammatory diseases.  Current activities in the lab are looking at roles of oxidative stress and the reductases systems in the initiation and progression of cancers.  By integrating GEM models with alterations in the redox systems into cancer studies, new insights are being gained that could help uncover new therapies.