Protecting the heart from cardiac infarction

The only way to save the heart from an acute coronary infarction is by rapid reopening (reperfusion) of the blocked coronary vessel. Compared with rapid reperfusion, a delayed or staccato type of reperfusion is associated with less reperfusion damage and can thus reduce the size of the infarction. Professor Gerd Heusch from the Institute of Pathophysiology recently identified the activation of the transcription factor STAT3 in mitochondria (the “power plants” of the cell) as a key mechanism in providing the protective ­effect of this staccato reperfusion. This insight may make it possible in future to deliberately ­activate this mechanism without manipulating the coronary vessel.


On how the immune system recognizes bacteria

Defending against infection depends on certain molecular patterns (so-called PAMPS) being recognized by receptors of the innate immune system. Within this group of receptors, the Toll-like receptors (TLR) are of special importance. Professor Carsten Kirschning and his research team have now been able to identify a new PAMP receptor pair, consisting of 23S rRNA and TLR13. These findings substantially broaden knowledge of the development of bacterial infections and suggest that the use of RNA as an amplifier of the immune response may be a promising option to optimize vaccination.


Why the immune system fails to ward off some tumour

Due to their immunosuppressive activity, regulatory T cells (Tregs) play an important role in controlling a multitude of immune reactions. However, they not only prevent excessive immune responses, they may also inhibit useful reactions such as defence against tumours. An interdisciplinary research group led by Professor Wiebke Hansen and Dr. Iris Helfrich has now been able to elucidate a mechanism responsible for the infiltration of Tregs into tumour tissue. Tregs express Neuropilin-1 that, together with the VEGF released by the tumour cells, plays a key role in the infiltration process. These findings may form the basis of new strategies in cancer therapy.


New oncogene identified

An international research group led by Professor Johannes Schulte has been able to identify Lin28b as an oncogene and provide evidence of its mechanism of action. Lin28b binds to certain microRNAs, short, non-coding RNAs, that inhibit the translation of mRNAs into proteins. In neuroblastoma cells, Lin28b is highly expressed, for example due to an amplification of the Lin28b gene. Binding of Lin28b to microRNAs represses their inhibitory properties. This results in a massive upregulation of another oncogene, MYCN, that in turn promotes the growth and the division of certain cancer cells. The development of inhibitors of Lin28b may therefore be a promising strategy in cancer therapy.


A new therapy and its risks

Transcatheter aortic valve implantation (TAVI) is a novel, minimally-invasive treatment option for inoperable and high-risk patients with severe, symptomatic aortic valve stenosis. Researchers from the West German Heart Center Essen have recently shown by real-time procedural monitoring using transcranial Doppler ultrasongraphy that cerebral microemboli occur during all steps of the procedure, predominantly during manipulation of the calcified native valve while positioning and implanting the bioprosthetic stent-valves. These observations corroborate the findings of a previous study demonstrating a high incidence of silent embolic cerebral lesions on post-procedural diffusion-weighted magnetic resonance imaging and imply that future developments in the field of TAVI should also be directed towards a reduction of periprocedural cerebral embolization.


On the cellular origin of CLL

The cellular origin of chronic lymphocytic leukemia (CLL), the most frequent cancer of the immune system, has so far been unknown. Using transcriptome analyses of CLL and the main normal B cell subsets, Professor Ralf Küppers and his team were able to show a high degree of similarity between the leukemia cells and a special, rare subset of B cells of the peripheral blood. These cells are characterized by the expression of the surface molecule CD5 and display a resting, immunologically inactive phenotype as well as an expression pattern that is different from “conventional” B cells. These insights into the disordered gene expression and altered activation of signalling pathways may permit development of a targeted therapy for this as yet incurable cancer.


Better diagnosis – longer life

The analysis of sentinel lymph nodes is an important tool in the diagnosis of tumours such as malignant melanoma. If the sentinel lymph nodes that directly drain the tumour display tumour cells, it is likely that metastases have already developed in the vicinity. Examination of the sentinel lymph nodes is therefore important for diagnosis and the choice of therapy options. A study by the Department of Dermatology has now been able to demonstrate that a new technology, the preoperative hybrid single-photon emission computed ­tomography/computed tomography (SPECT/CT), is superior to standard methods of metastatic node detection. This method not only allowed more sentinel lymph nodes to be detected, the subsequent adapted therapy also yielded extended disease-free survival.