Matthias Kieslinger: Boning up on bone cancer
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- Matthias Kieslinger is a junior group leader at the Helmholtz Center Munich. Source: Matthias Kieslinger
11.01.2012 -
Matthias Kieslinger is research group leader at the Institute for Clinical Molecular Biology and Tumor Genetics at the Helmholtz Center Munich. In his research, the biologist is focused on the so-called EBF transcription factors. These regulate the formation of proteins that are normally involved in the formation of blood cells and bone. More recently, it has become clear that EBFs appear to play at the very least an indirect role in the formation of secondary tumours in bone cancer.
Matthias Kieslinger originally had little to do with the field of cancer. “The cancer project was not really our focus,” he admits. Instead, at the beginning of his research, the junior research group leader at the Institute for Clinical Molecular Genetics and Tumor Biology of the Helmholtz Center Munich posed two specific questions: How is blood formed in the bone marrow, and how does bone formation actually take place? The focus hereby is on a family of four proteins, the so-called Early B-Cell Factors (EBF1 to EBF4). “The EBFs are proteins that bind to the DNA, and in doing so activate specific genes,” explains Kieslinger. “This means that they are transcription factors.”
In the niche: EBF essential for blood-forming stem cells
More cells, for example the niche cells, are needed for the optimal provision of stem cells in the bone marrow. This is where the EBF proteins come into play: “We have been able to demonstrate that the expression of EBF2 in the niche cells is important in order to be able to retain the stem cells,” says the 42-year-old. The precise effect of the transcription factors is not yet fully clarified. Above all, the expression of immature osteoblasts EBF2 – the cells responsible for bone formation – appears to be important for the survival of similarly immature blood-forming stem cells.
First blood stem cells, then tumor stem cells
“We are actually the only people who can analyse these primary niche cells in a living organism,” says Kieslinger, with justified pride. “So we said, let's also take a look at the mirror image of normal blood cell formation.” Since that time, the group has investigated whether tumour stem cells occupy the same niche as normal blood stem cells. As part of the research group Skelmet – mesenchymal and osteogenic pathways in bone metastasis, which is funded with three million euros from the German Research Foundation (DFG), Kieslinger’s group is now studying the development of a specific kind of bone cancer: multiple myeloma. His working group is hoping to clarify which cell types and which stages of bone-building osteoblasts support the growth of cancer cells during multiple myeloma.
“There is still no clear data on this, but with our animal model, we have a good chance of shedding some light on these issues,” says Kieslinger. For their work, his group has been using a special mouse strain, in which the osteoblasts are unable to form the EBF2 protein. If the transcription factor indeed turns out to be key to the implantation of cancer tumours in the bone marrow, the course of the disease would differ greatly between normal and knockout mice.
At the interface between haematology and osteology
The Austrian Kieslinger found himself in Munich somewhat by chance. “After my graduation, I was looking for a good postdoctoral position,” he recalls. The Bavarian capital was one of the regional lighthouses for research into cellular differentiation. In 2001, Kieslinger began his postdoctoral research in the laboratory of Rudolf Grosschedl at the Ludwig Maximilians University Munich gene centre. Five years later, he became a junior research group leader at the Institute for Clinical Molecular Biology. “To leave my mentor and then take responsibility for my own working group was an exciting step,” says Kieslinger frankly. And yet: Because his team researches both the formation of blood as well as bone structure, he has created something unique. “I think it makes perfect sense to connect the two topics. The formation of blood takes place in the bone, and the cells interact with each other; nevertheless these are frequently separate fields,” says Kieslinger.
Haematologists and bone researchers often keep to themselves, so creating a connection here is important to me.”
Working for those moments of happiness
To this day, Kieslinger retains a genuine enthusiasm for biology: “The fascinating thing about biology is that you can arrive at a mechanistic understanding of natural processes,” says the biologist. “You can find out how something works, right to its innermost core.” Kieslinger draws his motivation from the success of his work: “Just now, when three PhD theses have come to an end in my group in a short time, there have been many of those happy moments that you work towards.” With a newly bred mouse line, his group was the first ever to demonstrate that that the removal of a single gene in niche cells is sufficient to prevent the development of blood-forming stem cells. “That really was fun.”
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