The GE11 group ‘Redox proteins in pathophysiological processes’ is an emerging IMIBIC group currently composed of 9 members including 4 postdoctoral researchers, 3 predoctoral researchers and 2 health researchers. Our main object of study is the redox regulation exerted in both physiological and pathological processes by a group of proteins known as ‘redoxins’ (glutaredoxin, thioredoxin, peroxiredoxin). These enzymes are responsible both for controlling the redox state of critical cysteine residues in target proteins (glutaredoxin and thioredoxin) and for removing hydrogen peroxide and peroxidised lipids (peroxiredoxin), which means that they are involved in the regulation of a wide variety of cellular processes ranging from intermediary metabolism to signalling pathways related to cell proliferation, cell death and differentiation.
Our group carries out eminently basic research, with objectives in which our results can shed light on the molecular and cellular bases of pathologies such as cancer and neurodegenerative diseases. However, our projects have a strong translational component, applying this basic knowledge to experimental models in vitro (cell lines) and in vivo (organoids from human biopsies) with the aim of implementing diagnostic and treatment methods based on our results, such as the use of lipid nanoparticles loaded with interfering RNAs and/or drugs for the silencing and inhibition of target proteins.
The group has regular funding thanks to obtaining competitive projects from regional and national agencies and, as an emerging IMIBIC group, it intends in the near future to apply for European calls for proposals and to establish agreements with pharmaceutical companies with which it has already established contact.
We collaborate with different groups both nationally and internationally and with other IMIBIC groups, which allows us to cover different approaches in pathologies such as cancer and Parkinson's disease in which redox homeostasis plays a decisive role.
Lines of Research
Thioredoxin (Trx) and Glutaredoxin (Grx) are two enzymes that protect cells against oxidative stress and our research group has shown that they can also act as redox switches regulating metabolic fluxes, such as the production of energy from glucose or lipids. This is especially relevant in cancer and nerve cells. We therefore aim to investigate the role of these enzymes on the phenotype of these cells and how their expression levels affect drug resistance in tumour cells.
Role of peroxiredoxin 6 as peroxidase and phospholipase in signalling, proliferation and cell death.
Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme, unique within the Prdxs family and exclusive to some mammals including humans. This enzyme is overexpressed in both cancer and neurodegenerative diseases, inducing tumour progression in the first case and neuronal death in the second. Within this line we try to decipher the molecular mechanisms by which PRDX6 exerts its function and the differential roles of each of its activities.
Post-transcriptional redox modifications of reactive cysteines alter the functionality of key proteins in both cancer and neurodegenerative diseases. This line of our group focuses on the study of these redox changes capable of altering the mechanisms of tumour progression or accelerating neuronal death and their relationship with endogenous redox control systems. This allows us to identify new therapeutic targets and new diagnostic markers and from these we are developing new treatment strategies based on the inhibition of key proteins through the use of functionalised lipid nanoparticles specifically directed at the target cells.
Networks
BenBedPhar – COST Action CA20121. 2021-2025. Network for Research in Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases. Research and Innovation Framework Programme Horizon Europe.
Grupo PAIDI BIO-216 – Proteínas redox en procesos celulares y fisiopatológicos
Key Words
- Oxidative stress
- redoxins
- mitochondria
- Thioredoxin
- Glutaredoxin
- Peroxiredoxin 6
- cell proliferation
- cell death
- metabolism
- signalling
- hepatocarcinoma
- colon cancer
- neurodegeneration
- Parkinson's disease.
