Transcriptional responses to signals and hormones

Dr. Franziska Greulich

Gene expression changes in response to signaling cues like stress, infections, nutrition, circadian rhythms etc. are the basis of any cellular response. Every cell reacts in a specific way, depending on the tissue type or signaling pathways. Our aim is to understand transcriptional circuits and to describe the complexity of transcription factor interactions with co-regulators and the chromatin landscape using molecular biology, biochemistry and next-generation sequencing technologies.

Projects

1. Nuclear interaction partners of the glucocorticoid receptor

We performed chromatin-immunoprecipitation with subsequent mass spectrometry (ChIP-MS) to identify nuclear interaction partners of the glucocorticoid receptor in macrophages, liver and mouse embryonic fibroblasts (MEFs). Feel free to browse the results of those experiments here: https://franzig.shinyapps.io/grinteractors/
We are currently investigating the functions of some of those interaction partners in glucocorticoid-dependent inhibition of inflammation or regulation of metabolism.

2. Reversibility of long-term glucocorticoid effects

In this DFG funded project, we look at the long-term effects of glucocorticoid therapy in murine tissues. Glucocorticoids are widely prescribed to treat inflammatory diseases. The aim of this project is to understand glucocorticoid effects in non-immune cells to evaluate mechanisms involved in the adverse effects of glucocorticoid therapy. This project is a cooperation with Dr. Sabine Vettorazzi at the University of Ulm. We are using mouse models, histology, molecular biology, next-generation sequencing and single-cell analysis. We are looking for master students as well as student aids (HIWI) soon. If you are interested in this project, please contact me directly.

3. Context-specific glucocorticoid receptor actions

Glucocorticoid actions are not only tissue-specific but also depend on the cellular context. Furthermore, we could recently show that the glucocorticoid response in macrophages depends on different co-regulators and the gene locus (10.1016/j.celrep.2021.108742, https://doi.org/10.1101/2021.12.13.472398). Here, we explore this locus-specific control of gene regulation by the glucocorticoid receptor using CRISPR/Cas9, next-generation sequencing and molecular biology techniques.

4. Nuclear hormone receptor function in arteriosclerosis

A high-fat so-called Western Diet exacerbates arteriosclerosis. This progressive process takes years in humans. Nuclear hormone receptors are transcription factors able to sense environmental cues, many of whom are part of the Western Diet. In this project, we explore the contribution of nuclear receptor signalling in macrophages to the formation of arteriosclerotic plaques.

Alumni

Master students

  • Anood Sabir (Nutrition and Biomedicine, 2016) "Development of genetic engineering tools to study the effects of the COMPASS complex on glucocorticoid receptor-mediated anti-inflammatory responses in macrophages"
  • Drilona Llolluni (Biochemistry, 2022) "Transcriptional regulation of inflammatory signaling in macrophages by the histone methyltransferase SETD1A"
  • Noémi Mallet (Nutrition and Biomedicine, 2022) "Role of the testicular receptor 4 (TR4) in macrophage inflammation"

Bachelor students

  • Eva Skarke (LMU Chemistry and Biochemistry, 2019) “The interaction between the Glucocorticoid Receptor and isoforms of transcription factors AP-1 and NF-κB”
  • Helena Althammer (Nutritional Science, 2020) "The Transcriptional Control of Inflammatory Reactions by Synthetic Glucocorticoids"
  • Hanna Hofrichter (Nutritional Science, 2020) "The Effect of Glycolysis Inhibition on the Anti-inflammatory Actions of the Glucocorticoid Receptor in Human Macrophages"
  • Leonie Winter (Nutritional Science. 2021) "Establishment of an inducible degradation system in macrophage cell lines"