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Portrait Darja Andreev

The immune system is the human body's defense mechanism. It protects us from foreign substances and pathogens including helminths, bacteria and viruses. However, various genetic, epigenetic, and environmental factors can cause the immune system to malfunction, resulting in autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease, or hypersensitivity reactions such as allergic asthma. These chronic conditions require patients to continuously adjust their medication and remain on it for a lifetime, posing significant health and economic burdens to both patients and society. Our research focuses on investigating potential cellular and molecular signaling pathways that lead to misguided immune responses and using this knowledge to promote the resolution of chronic diseases and restore tissue homeostasis.

Another important aspect of our research is the investigation of cellular and molecular mechanisms that counteract pathological bone turnover as it is the case in postmenopausal osteoporosis and rheumatoid arthritis. Here we focus on the crosstalk between innate immune cells and bone cells including bone resorbing osteoclasts, bone forming osteoblasts and bone-resident osteocytes.

At TUD, we are committed to staying at the forefront of scientific research by consistently investing in novel imaging and omics technologies. I offer compelling research topics for driven and enthusiastic PhD candidates who are eager to tackle pivotal questions in immunology.

Role of heme peroxidases as pro-resolving agents in inflammatory arthritis

The objective of this project is to uncover a novel immune regulatory function of heme peroxidases in rheumatoid arthritis. These peroxidases are produced in high amounts by granulocytes and can be found in arthritic joints. Traditionally, their role has been to generate reactive oxygen species (ROS) as a defense mechanism against invading pathogens. However, recent research suggests that heme peroxidases have a much more intricate role in the immune system, possessing not only proinflammatory properties but also various immune-modulatory effects.

The main focus of this project is to investigate how heme peroxidases may promote the transition of classical proinflammatory macrophages to alternatively activated macrophages with anti-inflammatory qualities, thereby facilitating the resolution of inflammatory arthritis.

Regulatory functions of eosinophils during pathological bone remodeling

The equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts is crucial for maintaining a healthy skeletal system. However, hormonal changes as during the menopause or inflammation, such as in rheumatoid arthritis, can disrupt this balance by enhancing the development of osteoclasts, which leads to low bone mass and an increased risk of fractures. While the pro-osteoclastogenic effects of immune cells and cytokines, such as TNFα, IL-1β, IL-6 and IL-17A have been extensively studied, the immune cells and mediators that inhibit osteoclast formation are not well understood.

Type-2-immunity-related cytokines, which are secreted in high amounts by eosinophils, have been found to suppress osteoclast differentiation and function. However, the regulatory role of eosinophils in bone health has been largely overlooked. Therefore, the objective of this project is to enhance or comprehension of how eosinophils regulate pathological bone decline as observed in postmenopausal osteoporosis and inflammatory arthritis and identify novel therapeutic approaches for these conditions.

Darja Andreev Research: Figure
Figure: In vitro-generated, multinucleated osteoclast. These cells engage in bone resorption through attachment to the bone surface using podosomes (highlighted by f-actin staining in red).

Future Projects and Goals

  • Exploring the cellular and molecular processes underlying immune system dysregulation, leading to autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease, as well as hypersensitivity reactions such as allergic asthma.
  • Exploring the role of eosinophils beyond tissue inflammation, delving into their regulatory functions within the body.
  • Understanding the mechanisms behind bone deterioration linked to damage and aging, with a specific emphasis on the interplay between immune cells and bone cells, notably osteoclasts responsible for bone resorption.

Methodological and Technical Expertise

  • Omics-technologies (single cell RNA sequencing, bulk RNA sequencing, proteomics)
  • Imaging (light-sheet fluorescence microscopy, confocal microscopy, transmission electron microscopy, micro-computed tomography, immunofluorescence, histomorphometry)
  • Cell metabolism analyses (extracellular flux assays, SCENITH technology)
  • Flow cytometry and fluorescence activated cell sorting
  • Immunological methods (real-time quantitative PCR, ELISA, Western blot)
  • Implementation of autoimmune mouse models
  • Cell culture (murine und human osteoclast and macrophage primary culture, osteoblast and osteocyte cell lines)
  • CRISPR/Cas9 gene editing of monocyte-derived primary cells

Currently Recruiting

Darja Andreev is recruiting in the PhD Summer Selection 2024 (call is closed)

Open Project
  • Unraveling the mechanistic role of heme peroxidases in the polarization of pro-resolving macrophages during inflammatory arthritis
    Preferred Course of Study/Expertise of Candidate: Immunology, Cellular and Molecular Biology
    → Detailed information as PDF


As of Summer 2024
Junior Research group leader, Center for Regenerative Therapies Dresden, Germany

Junior Research group leader, Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Germany

Postdoctoral fellow, Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Germany

Dissertation in Biology (Dr. rer. nat.), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Germany

Bachelor in Biology and Master in Cellular and Molecular Biology, Friedrich-Alexander Universität Erlangen-Nürnberg, Germany

Selected Publications

D Andreev, K Kachler, M Liu, Z Chen, B Krishnacoumar, M Ringer, S Frey, G Krönke, D Vöhringer, G Schett, A Bozec
Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase
Nat Commun 15(1):1067 doi: 10.1038/s41467-024-45261-8 (2024)

D Andreev*, K Kachler*, G Schett and A Bozec
Rheumatoid arthritis and osteoimmunology: The adverse impact of a deregulated immune system on bone metabolism
Bone 162: 116468 doi: 10.1016/j.bone.2022.116468 (2022)

D Andreev*, M Liu*, K Kachler, ML Perez, P Kirchner, J Kölle, A Giessl, S Rauber, R Song, O Aust, A Grüneboom, A Kleyer, JD Caneté, A Ekici, A Ramming, S Finotto, G Schett and A Bozec
Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis
Ann Rheum Dis 80(4):451468 doi: 10.1136/annrheumdis-2020-218902 (2021)

D Andreev, M Liu, D Weidner, K Kachler, M Faas, A Grüneboom, U Schlotzer-Schrehardt, LE Munoz, U Steffen, B Grötsch, B Killy, G Krönke, AM Luebke, A Niemeier, F Wehrhan, R Lang, G Schett and A Bozec
Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin
J Clin Invest 130(9):48114830 doi: 10.1172/JCI134214 (2020)

Z Chen*, D Andreev*, K Oeser, B Krljanac, A Hueber, A Kleyer, D Voehringer, G Schett and A Bozec
Th2 and eosinophil responses suppress inflammatory arthritis
Nat Commun 7: 11596. doi: 10.1038/ncomms11596 (2016)