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23.01.2012

Peter Rodemann – a career in radiobiology

Prof. Dr. H. Peter Rodemann has been head of the Division of Radiobiology and Molecular Environmental Research at Tübingen University Hospital for around 20 years. He has been awarded numerous prizes for his outstanding achievements, particularly during the second half of 2011 when he was awarded the Ulrich Hagen Prize by the German Society for Biological Radiation Research as well as being elected member of the German Academy of Sciences Leopoldina.


Prof. Dr. H. Peter Rodemann has been awarded numerous prizes for his achievements in radiobiology. (© private)

Membership of the German Academy of Sciences Leopoldina is an honourable distinction. Scientists cannot apply for membership themselves. The academy was established as early as 1652 and is the oldest in the world; it focuses mainly on the natural sciences and medicine and only confers honorary membership in recognition of outstanding scientific achievements to scientists directly proposed by renowned scientists. Following his election, Rodemann now joins other famous scientists who were members of Leopoldina such as Albert Einstein, Niels Bohr, Marie Curie and Charles Darwin, to name but a few.

The radiobiologist from Tübingen is well aware of the fact that the Leopoldina membership is more than just a distinction. "In July 2008, the Leopoldina was appointed the German National Academy of Sciences. As such, the Leopoldina offers practical advice on political, social and economic issues and it would therefore be natural for me to get involved in such issues. It goes without saying that I am very keen to discover national boards from an insider’s viewpoint and to be able to contribute to shaping research institutions." Prof. Rodemann will get a feel for how it all works over the next few months before he is officially inducted into the Leopoldina in summer 2012. On 13th September 2011, Rodemann was awarded the Ulrich Hagen Prize by the German Society for Biological Radiation Research for his long-term achievements in the field of radiobiology.

The cell biologist developed a fascination for research into the effects of radiation on biological systems very early on in his scientific career. Following his biology studies and his doctoral degree from the University of Hohenheim in 1979, Rodemann spent a three-year postdoctoral period at Harvard University Medical School in Boston, USA. “Initially, my work concentrated on cellular interactions which lead to the degradation of proteins under conditions of stress such as sepsis and as a result of certain pathophysiological situations,” said Rodemann.

Research into the mechanisms of cell differentiation, ageing and death caused by radiation

When he returned to Germany, Rodemann continued his work in the field of cell biology: in 1986, he habilitated at the University of Hohenheim with a study on the regulation of the protein metabolism in differentiating cell systems, including cells that are exposed to radiation. In 1987, Rodemann was awarded a Heisenberg scholarship by the DFG for studies at the University of Bielefeld where he investigated the pathomechanisms of cellular interactions in one of the university’s collaborative research centres. His research also involved the comparison of normal and irradiated cells and organs. “Ionising and UV radiation are known to induce cell ageing. It is also known that cells age the more quickly the less effective the cellular repair mechanisms are. The major question therefore relates to finding out which factors influence such processes,” said Rodemann.

Tumour cells can be made highly sensitive to radiotherapy. The light red spots reveal DNA damage in tumour cell nuclei (immunofluorescent staining of the gamma-H2AX foci). A) Cell nuclei of tumour cells that are resistant to therapy, B) nuclei of cells of the same tumour treated with an inhibitor that interferes with their repair capacity, thereby causing greater DNA damage (visualized by stained gamma-H2AX foci). (© Prof. Rodemann, University of Tübingen)

 

These issues touch on radio-oncology, which seemed to be a natural area for Rodemann to concentrate his future efforts on. After he was appointed professor for radiobiology at Tübingen University Hospital, Rodemann got involved in research into the effect of radiotherapy on cells and tissues. Pulmonary fibrosis, for example, occurs when lung tissue is damaged, for example as a result of exposure to radiation. “A fully differentiated cell has a specific life span. The exposure of normal tissue to radiation induces the premature terminal differentiation process which leads to the accumulation of collagen. As more collagen accumulates, respiration is made difficult and prevents the normal supply of oxygen to the lungs,” said Rodemann explaining the adverse effects of radiation exposure.

Rodemann and his team were the first to elucidate the cellular and molecular processes of radiation-induced pulmonary fibrosis and other lung diseases resulting from lung tissue alterations. As cells of normal, i.e. healthy tissue, differ in their sensitivity to radiation, the results also have the potential to contribute to the development of a test system that would make it possible to optimise the planning of the radiation regimen: the irradiation of cell cultures derived from a patient’s own cells and the analysis of radiation-induced effects would make it possible to assess the effects of radiation and adjust the radiation dose to individual patient requirements. “What we find is that the sensitivity to radiation has the normal, i.e. Gaussian, distribution. Some people have cells that are particularly sensitive to radiation whereas others have cells that are not sensitive at all. The cells of patients who are highly sensitive to radiation and who develop radiation-induced pulmonary fibroses undergo an early terminal differentiation process,” explains Rodemann.

 

Radioprotectors induce cellular repair mechanisms

The clarification of radiation-induced molecular mechanisms enabled Rodemann’s team to develop so-called radioprotectors, special, non-toxic proteins that reduce the likelihood of radiation-induced effects developing in healthy cells when given before/during irradiation. Rodemann and his team already own several patents for such radioprotective agents. The agents the team uses are specific for tissue characterised by functional wild-type p53 tumour suppressor proteins. “Radioprotective agents put normal cells into a state of emergency, which causes them to initiate DNA repair mechanisms much earlier than they would otherwise. Around 60 to 70 per cent of all tumours treated with radiotherapy are characterised by mutated, non-functional p53, in which case the radioprotective agents do not protect the tissue. The agents therefore selectively protect cells with functional p53. Tumour tissue with non-functional p53 is thus destroyed through radiation,” said Rodemann touching upon potential interactions between p53 and the radioprotectors and the assumption that phosphorylation signalling cascades play a major role in such interactions. The researchers from Tübingen have been focusing on the molecular mechanisms involved for quite some time. “We assume that changes in the activity of enzymes such as kinases and phosphatases put cells into an emergency state,” said Rodemann.

The cosmetics industry is also interested in radioprotectors as they not only protect against ionising radiation, they also protect against UV radiation, which makes them suitable ingredients in sunscreen and other skin protection products. Rodemann’s team is already in contact with suitable partners from the pharmaceutical and cosmetics industry who are interested in utilising the protective agents.

In addition to research into the protection of healthy tissue against radiation, Rodemann is also focused on the opposite end of the scale to protection, namely finding ways to increase the radiosensitivity of tumour tissue. This combination of searching for ways to effectively protect normal tissue against radiation doses that are as high as possible with research into ways of increasing the sensitivity of tumours to radiation is the basis of the team’s success. “In contrast to chemotherapy, which is mainly focused on palliative care, radiation therapy is in principle curative, although it is associated with a certain risk. Our goal is to reduce this risk and find ways to kill tumour cells as effectively as possible,” said Rodemann. Given the fact that over 180,000 radiation therapies are carried out in Germany every year, the effective destruction of tumour cells and the reduction of the risk involved would not only benefit individual patients, but also the health system as a whole.

“That which only functions at 50% capacity, dies more quickly”

Rodemann plans to increase the sensitivity of tumours to radiation by interfering with cellular signalling. Rodemann’s team was the first team of researchers in the world to show that the receptor of the EGF growth factor controls and improves the repair of radiation-induced DNA damage. The EGF receptor is overexpressed in many tumours, which makes them resistant to radiation as well as chemotherapy. "Inhibiting the EGF receptor signalling pathway prevents the effective repair of DNA damage. And a tumour cell that only functions at 50% capacity, dies more quickly, giving patients a survival advantage", said Rodemann. A particularly interesting option in terms of interfering with cellular signalling is the development of a special cocktail of radioprotectors and receptor blockers, in which the radioprotectors need to be specific for normal tissue while the receptor blockers specifically target tumour cells.

In addition to carrying out research, Rodemann also has plenty of challenges to deal with in the field of education. Rodemann was involved in establishing the interuniversity medical technology study programme at the Interuniversity Centre for Medical Technologies Stuttgart-Tübingen. The establishment of the study programme was no easy matter, particularly in terms of organisation, as students do online courses as well as attending classes at both universities, which are around 40 km apart. “Sometimes the logistics involved reminds me of the quadrature of the circle,” said Rodemann smiling. The programme is now well underway and is being overseen by Rodemann in his role as dean of studies at the University of Tübingen. Rodemann also offers radiobiology courses for students in the molecular medicine and medical technology study programmes and is also involved in the establishment of master’s degree courses in molecular medicine and medical technology.
A contribution from:
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leh (20.12.11) - 23.01.2012
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