Research
Regulation of Gene Expression and Signal Transduction Pathways in the Endocrine and Nervous System
My laboratory studies gene transcription and signal transduction pathways primarily in cells of the endocrine and nervous systems. The research in the laboratory is focused on the biochemistry and molecular biology of two types of transcriptional regulators, zinc finger proteins (Egr-1, Sp1) and basic region/leucine zipper proteins (CREB, c-Jun, c-Fos, ATF2-5, Nrf2, CHOP). In addition, we are interested in elucidating the role of stimulus-induced protein kinases and second messengers in stimulus-transcription coupling.
Within the endocrine system, we are particularly interested in analyzing signal-induced gene transcription in the following:
- beta cells of the pancreas,
- gonadotrope cells from the pituarity,
- adrenocortical cells from the adrenal cortex.
Our principal objective is to understand the communication between the stimulation of G-protein coupled receptors, receptor tyrosine kinases, ionotropic receptors, L-type voltage gated calcium channels, and TRP channels at the plasma membrane and the activation of a specific set of target genes in the nucleus. A precise stimulus-transcription coupling is necessary for the endocrine cells to regulate hormone biosynthesis and secretion and to assure the physiological functions of hormones within the organism.
The experiments encompasses the analysis of immortalized and primary cells in culture that are genetic altered by infection with recombinant lentiviruses. In addition, genetically modified mice are analyzed that express mutated transcription factors or receptors in a conditional manner (Tet-on system).
Regulation of Gene Transcription by Phytochemicals
Many plant substances have been reported to exhibit antioxidative and anticarcinogenic activity. Many of these substances are ingredients of nutrients, i.e. resveratrol from grapes, capsaicin from chili pepper, or sulphoraphane from broccoli. We are interested in elucidating the role of these compounds on intracellular signaling cascades and the regulation of gene transcription. In these studies, the activity of redox-sensitive transcription factors such as Nrf2, AP-1 and Egr-1 are of particular interest. We think that the antioxidative and anticarcinogenic activity of phytochemicals is based on an altered genetic expression program involving stimulus-responsive transcription factors as common targets.
