New thesis investigates how corepressors control gene activity in macrophages
Astradeni Efthymiadou from the Gastroenterology and Nutrition Unit (GUT), at the Department of Medicine, Huddinge (MedH) defends her thesis titled "Understanding corepressor complex function in the epigenetic regulation of macrophage gene expression", on 21 November, 2025. Main supervisor is Eckardt Treuter (MedH).
What is the main focus of your thesis?
My thesis investigates how molecules called corepressors control gene activity in macrophages through epigenetic mechanisms. I study how these proteins act together and separately to switch genes off, which can push macrophages toward more inflammatory or more inflammation-resolving states.
Which are the most important results?
We especially focused on three corepressors: GPS2, NCOR, and SMRT. Earlier work from our group showed that GPS2, together with SMRT, helps restrain inflammation in pro-inflammatory macrophages. In Study I of this thesis, we found that GPS2, together with both NCOR and SMRT, switches off anti-inflammatory genes in alternatively activated macrophages. Study II revealed that although NCOR and SMRT are closely related, they have different functions: NCOR mainly regulates metabolism-related genes, while SMRT influences inflammation-related genes. The study also showed that SMRT plays the dominant role of keeping NCOR and GPS2 bound to DNA to carry out their regulatory functions.
How can this new knowledge contribute to the improvement of people’s health?
Many chronic diseases, such as type 2 diabetes, atherosclerosis and cancer, are worsened by harmful macrophage activity. By pinpointing how GPS2, NCOR, and SMRT tune macrophage gene programs, our work suggests new ways to “reprogram” macrophages toward healthier states, potentially improving treatments for these conditions.
What are your future ambitions?
I plan to continue research on gene regulation, expanding beyond corepressors to include how chromatin structure and genome organization influence when genes are turned on or off in health and disease. My aim is to combine experimental and computational approaches, with the long-term goal of translating basic insights into more precise therapies.
Dissertation
Monday, 24 November, at 10:00, Gene in Neo, Blickagången 16, Flemingsberg.