Biomedical Science

Research at the ZMB is structured into four research programmes, which are presented below in selected projects.

Oncology

The Clinic for Dermatology, headed by Professor Dirk Schadendorf, focuses in particular on the study of prognosis and resistance of malignant skin cancer. To date, there have been no therapy options that can prolong life. In 2010, the first reports were made of a substance (Ipilimumab) that exhibited a survival benefit in an advanced stage of melanoma when applied in immunotherapy. New molecular pathological findings have now led to the development of novel substances. This led to the development of a targeted therapy that uses a tyrosine kinase inhibitor. This was based on the knowledge that black skin cancer presents certain alterations in its tumour cells known as BRAF mutations. The new drug (Vemurafenib) selectively inhibits specifically mutated BRAF and thus attacks there only, leading to a fast reduction even in large tumours. This substance has already been approved in the USA, where the approval study also showed a survival benefit. The drug will become available in Europe in early 2012.

Immunology, Infectious Diseases and Transplantation

The work group of Professor Elke Cario at the Clinic for Gastroenterology and Hepatology studies the function and regulation of the intestinal epithelium. Receptors that specifically recognize bacteria play a key role in the immune defence of the digestive tract. The TLR4 polymorphism D299G, which was recently described as a risk factor for various diseases, was identified for the first time by Cario’s team as a gain-of-function mutation in the intestinal epithelium. Overexpression of the mutation leads to disturbed construction of the actin cytoskeleton and major disturbances in cell division. One study found that patients with the mutation more often exhibited an advanced stage of cancer with metastasis upon diagnosis, which indicates especially aggressive growth behaviour in the mutated cancer cells.

Genetics, Developmental, Molecular and Cell Biology

The work group of Professor Hemmo Meyer explores the molecular mechanisms that regulate cellular signal and repair processes and thus control cell division, for example, or react to external stimuli. Their main interest is in the protein VCP/p97, a kind of nanomachine that takes apart cell components and directs cellular decomposition. The group recently showed that VCP/p97 helps to dismantle components of the cell surface. This function could explain certain degenerative processes in myopathies. The group also showed that VCP/p97 plays a central role in DNA repair processes. DNA damage takes place naturally, but it is also generated therapeutically to kill cancer cells. VCP/p97 therefore plays an important role in genomic stability and could provide a starting point for new cancer therapies.

Biomolecular Structure and Function

A combination of experiments and simulations provided one international research group with some surprising findings on short protein-like molecules that penetrate cells, known as cell-penetrating peptides (CPPs). Some of these peptides break through the cell membrane with the aid of transport proteins, while others manage it without any assistance; the mechanism underlying the latter is not yet understood. An important contribution to understanding one possible mechanism was made using atomic-resolution computer simulation of these peptides in aqueous solution in the Computational Molecular Evolution work group of Professor Daniel Hoffmann. They discovered that CPPs look like molecular porcupines, where the quills are made up of positively charged amino acids. This molecular shape could ease penetration of the cell membrane by the CPPs. These findings can be used to develop this type of peptide for medical or biotechnological purposes.