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Lisa van Weert, MSc

Molecular aspects of stress hormone signaling in the brain

Glucocorticoids (cortisol/corticosterone) can influence processes throughout the whole body: metabolism, immune system, cardiovascular function. I study their effector pathways in the brain, where glucocorticoids promote stress coping and modulate memory. Glucocorticoids can via transcriptional regulation have distinct effects, depending on the cell type you study. By investigating the interaction of the glucocorticoid receptor (GR) with other transcription factors and coregulators, I would like to get insight into which downstream pathways are responsible for which glucocorticoid effect. Ultimately this could provide us with more selective targets in stress-related pathologies, such as depression and post-traumatic stress disorder.

The mineralocorticoid receptor (MR) is another receptor for glucocorticoids. Despite the high structural similarity of MR and GR, and their binding to the same DNA sequences, the two receptors can mediate distinct and sometimes even opposing cellular responses. Through measuring whole genome DNA binding and subsequent transcriptional changes I aim to unravel the specificity of MR/GR signaling.

Furthermore, in collaboration with prof. Benno Roozendaal (Donders Institute/Radboud University Nijmegen), the molecular basis of glucocorticoid-potentiated learning is studied. Stress hormones are known to enhance the encoding of emotional events. Similarly, glucocorticoids can potentiate learning of rodents in an object location memory task, but this is dependent on noradrenalin signaling. I investigate if transcriptional interactions between those hormonal downstream mediators, GR and pCREB respectively, underlie this enhanced memory formation.