2016 Windaus Award for Dietrich Keppler
Dietrich Keppler, who was head of a research division at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) until 2007, has been awarded the 2016 international Adolf Windaus Award for his research achievements. Keppler, a biochemist, has made seminal contributions towards unraveling the molecular mechanisms of how substances are transported into the liver and from the liver into the bile. The Windaus Award has been given by the Falk Foundation since 1980 for outstanding achievements in the field of bile acid research. The award comprises €15,000.
© Yan de Andres
The liver excretes many substances that are useless or toxic for the body into the bile. One of these substances, for example, is bilirubin, which is the metabolite of hemoglobin, the pigment in the red blood cells. If this excretion process is disrupted, blood levels of the yellow bile pigment bilirubin rise, resulting in jaundice. Keppler and his department elucidated the details of this substance transport.
Liver cells (hepatocytes) are equipped with various transporter proteins that mediate and regulate the import and export of substances. Keppler and the researchers working with him discovered that various members of the organic anion-transporting polypeptide (OATP) family are responsible for the absorption of bilirubin into the hepatocyte at the surface facing outwards towards the bloodstream. In contrast, various transporters of the multidrug resistance-associated protein (MRP) family facilitate the export into the bile canaliculi. Cancer researchers know these MRP transporters for their capability of pumping anticancer drugs out of tumor cells such that their levels in the tumor cell are often not high enough to be effective.
In addition to their function of facilitating substance transport from the liver into the bile canaliculi, transporter proteins play an essential role in the body. They are involved wherever substances and secretions are passed outwards via small channels or ducts, such as in the intestine or the mammary ducts. To enter these channels, all substances in the bloodstream intended for excretion must pass a layer of specialized epithelial cells that are equipped with transporter proteins.
Therefore, the results of Keppler’s comprehensive molecular analyses are of substantial importance and have been used across the globe in the development of new drugs for many years. Whenever agents are directed at targets in the cell interior, pharmacologists initially make sure that the appropriate import proteins are present. To this end, it is crucial to know which transporter is responsible for which substance in the specific tissue. In addition, it is possible to use highly-specific agents to block individual transporter proteins. These substances can thus be used to selectively influence the exchange of substances in the body.
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
