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Portrait Franziska Knopf

Although bone is a regenerative tissue also in humans, it can be permanently lost in circumstances of trauma, cancer or degenerative diseases. Due to their high regenerative capacity zebrafish have emerged as a powerful tool to study bone regeneration. In particular, bone forming and bone degrading cells (osteoblasts and osteoclasts) can be visualized easily in zebrafish, thus allowing their observation in the living organism. This can be used to monitor osteoblast and osteoclast function throughout processes of bone formation and bone degradation, and to study cross-talk of bone cells with other types of cells, such as immune and cancer cells, in the bone niche.

In the lab we make use of pharmacologic approaches and molecular biology tools to investigate adverse effects of certain drugs used in the clinics. We have analyzed the anti-regenerative effects of immunosuppressive glucocorticoids in zebrafish, in which bone forming osteoblasts are fluorescently labelled. In doing so, we found that both osteoblast activity and proliferation are reduced by glucocorticoid exposure. In addition to this, we are interested in uncovering the molecular impact of glucocorticoids on innate immune cells, which contribute to bone regeneration. To preserve bone strength, we aim for the identification of anti-inflammatory molecules counteracting bone destruction.

A main focus of the lab is to understand underlying mechanisms of successful bone regeneration. Zebrafish regenerate bone quickly after injury, both in appendages and the skull; however, they do not overgrow bone. How do they do so? To address this question, we explore ways of positively and negatively influencing tissue regeneration.  This is feasible both by drug treatments and genetic modulation. By using a combination of these approaches with state-of-the-art imaging technologies, we hope to identify mechanisms that are involved in growth control of bone and of regenerating tissues in general. Our in vivo imaging approaches are also employed to study the early metastatic events leading to tumor cell engraftment in bone tissue. Our work will have important implications for future regenerative therapies of the skeleton and help to identify targets to fight bone metastasis.

Franziska Knopf Research: Figure
Zebrafish caudal fin (left). Gene expression in the early regenerating fin (right).

Future Projects and Goals

We will exploit the regenerative capabilities and excellent imaging capabilities of zebrafish to

  1. investigate growth and patterning underlying successful bone regeneration,
  2. promote zebrafish as a preclinical model to characterize adverse effects of widely used anti-inflammatory steroids, and to
  3. better understand metastasis of cancer cells in bone.

Methodological and Technical Expertise

  • Bone injury models
  • Intravital microscopy in zebrafish
  • Genetic and pharmacological modulation of gene expression

CV

Since 2017
Group leader and W1 professor, CRTD and Center for Healthy Aging, TU Dresden, Germany

2016–2017
Postdoctoral research TU Dresden, Germany

2013–2015
Postdoctoral research University of Oxford, UK

2011–2012
Postdoctoral research TU Dresden, Germany

2011
PhD TU Dresden, Germany

2006
Biology Diploma HU Berlin, Germany

Selected Publications

Cudak N, López-Delgado AC, Rost F, Kurth T, Lesche M, Reinhardt S, Dahl A, Rulands S, Knopf F
Compartmentalization and synergy of osteoblasts drive bone formation in the regenerating fin
iScience 27, 108841 (2024)

Geurtzen K, López-Delgado AC, Duseja A, Kurzyukova A, Knopf F.
Laser-mediated osteoblast ablation triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish
Development 149(8):dev199803 (2022)

Dietrich K, Fiedler IA, Kurzyukova A, López-Delgado AC, McGowan LM, Geurtzen K, Hammond CL, Busse B*, Knopf F*
Skeletal biology and disease modeling in zebrafish.
J Bone Miner Res 36, 436–458, (2021)
*co-corresponding authors

Schmidt JR, Geurtzen K, von Bergen M, Schubert K*, Knopf F*
Glucocorticoid treatment leads to aberrant ion and macromolecular transport mechanisms in regenerating zebrafish fins.
Front Endocrinol 10, 674 (2019)
*co-corresponding authors

Geurtzen K, Vernet A, Freidin A, Rauner M, Hofbauer LC, Schneider JE, Brand M, Knopf F
Immune suppressive and bone inhibitory effects of prednisolone in growing and regenerating zebrafish tissues.
J Bone Miner Res 32, 2476–2488, (2017)

Contact

Center for Regenerative Therapies Dresden
TU Dresden
Fetscherstraße 105
01307 Dresden