Regulation of gene expression at the transcriptional and translational levels is fundamental to all biological activities and is frequently altered in disease states. Our broad research interests are to elucidate how the transcription and translation processes control the cellular response to enviromental stimuli, to reveal the connections between the two processes and to develop tools to manipulate them. To this end our aims are: (i) to understand mechanistic aspects of stress-induced transcription, focusing on the initiation and elongation stages; (ii) to unravel the molecular basis of translation mechanisms that are linked to transcription under normal and stress conditions; (iii) to identify drugs that target specific components of the transcription and translation machineries for the teratment of cancer, chronic inflammation and neurodegenrative diseases. We address these issues utilizing several biological systems:
- NF-κB, the major pro-inflammatory transcription factor
- Spt4/Spt5 (DSIF), a transcription elongation factor involved in stress responses and a prime target for inherited neurodegerative diseases
- TISU, a dual transcription and translation regulatory element
- Regulation of translation initiation by stress and mitogenic signals
Our long term goal is to achieve deeper understanding of various stages of gene expression with an emphasis on their involvement in diseases and drug development.