Regulatory mechanisms of steroid receptors - Niskanen lab

We investigate the mechanisms that regulate steroid receptor function. We use genome-wide, bioinformatic, and molecular biology approaches, along with models of cortisol and inflammatory signaling pathways that can be activated in cells in a controlled manner.

What factors influence the glucocorticoid (GC) response at the level of individual genes? Glucocorticoids act by activating the glucocorticoid receptor (GR), which regulates gene expression together with other transcription factors and coregulator proteins. The anti-inflammatory effects of GCs largely result from the repression of inflammatory genes, whereas side effects are linked to the activation of metabolic genes. The mechanisms leading to gene activation are relatively well understood, but those responsible for gene repression remain poorly characterized. Using cell models and genome-wide approaches (ChIP-seq, PRO-seq, RNA-seq, proteomics), we study these mechanisms, focusing on the role of coregulator proteins in GR regulation. We also examine how GC and inflammatory signals interact and integrate at the level of gene regulation.

Synthetic GCs are powerful anti-inflammatory drugs widely used to treat conditions such as asthma, rheumatoid arthritis, and hematologic malignancies. However, they can cause serious adverse effects, including diabetes and osteoporosis. Why do some patients develop these complications as a result of GC therapy while others do not? Genetic differences may influence how GR functions and which genes respond to GC treatment, leading to individual variation in side-effect profiles. We investigate these genetic differences using genome-wide association study-approach and the unique FinnGen resource, which combines genomic and health registry data from over half a million Finnish individuals.