Dept. of Biochemistry & Organic Chemistry

Research areas

Background - Glutathione transferases (GSTs)

Glutathione transferases (GSTs) form a superfamily of enzymes that have been extensively studied for their protective function as catalysts of the conjugation of the tripeptide glutathione to harmful electrophilic compounds. Recently, other physiological functions of GSTs have been uncovered, such as involvement in prostaglandin synthesis and regulation of stress-activated kinases. Expression of GSTs is regulated. Many xenobiotics (in particular electrophilic substrates) induce expression of GSTs, allowing a fine-tuned detoxication response. In addition, endogenous molecules (such as hormones) have been shown to affect GST expression. In spite of their pivotal role for in cell pathophysiology, only few mechanisms of GST regulation are understood in detail to date.
The aim of this program is to gain novel knowledge on gene expression control and on the various physiological roles of GSTs.

Endogenous functions of GSTs

In this program, recently proposed functions of GSTs, distinct from detoxication processes, are investigated. In particular the relevance of GSTs in steroidogenic processes in humans and in other mammals is studied.

Regulation of expression of GSTs

Inducibility is a property of GSTs which is critical for detoxication processes and probably for the endogenous pathways which GSTs may be involved in. We are studying how expression of GSTs is regulated both at the gene and at the transcript level. We are seeking to identify endogenous GST inducers and to study their involvement in physiological processes such as steroidogenesis.

The contemporary view of gene expression suggests that transcriptional and post-transcriptional processes act in concert to integrate the different steps along the gene expression pathway. Interconnections between transcriptional and post-transcriptional regulation of GSTs are investigated.

Research Projects

Physiological functions of glutathione transferases

• Human GSTA3-3 and biosynthesis of steroid hormones
• Identification of non-human mammalian alpha-class glutathione transferases involved in steroid hormone biosynthesis
• Modulation of steroidogenesis through inhibition of alpha-class glutathione transferases
• Control of expression of glutathione transferases (GSTs)
• Transcriptional regulation of GSTs
• Post-transcriptional regulation of GSTs
• Interplay between transcriptional and post-transcriptional mechanisms of regulation for GSTs
• Expression/function of GST splice variants

Group members

• Françoise Raffalli-Mathieu Assoc. Professor
  Project leader
  
• Emilia Larsson
• Fatima Burovic
  PhD Student
  

Undergraduate/MSc projects

• Description of the projects

Theses from the group

Publications and other contributions

• Publication list
• Publication database