Tracing the genetic causes of type 2 diabetes
With the appointment of Claudia Langenberg to BIH Professor of Computational Medicine, the Berlin Institute of Health (BIH) and Charité–Universitätsmedizin Berlin are strengthening and expanding their leading role in data-driven medicine. The genetic epidemiology expert and public health specialist examines the molecular mechanisms of metabolic diseases such as type 2 diabetes using large amounts of data from international patient and population studies. The BIH recruited the German-British researcher in early September from the University of Cambridge, where she was head of Molecular Epidemiology at the Medical Research Council (MRC) Epidemiology Unit.
Common chronic metabolic diseases such as obesity, insulin resistance and type 2 diabetes have both environmental and genetic causes. With obesity, for example, lack of movement and the excessive intake of high-calorie food play a role, but many genetic variants also increase the risk of putting on weight or of fat being distributed unfavorably. “We need huge studies with tens or hundreds of thousands of participants in order to be able to clearly determine the influence of individual genes, if only because we test millions of genetic variants,” says Claudia Langenberg, explaining the core of her research. “This requires the help of powerful software and computers.” Despite the relatively minor effects of individual variants, Langenberg explains, they can help scientists work out the causes of metabolic diseases, which in turn allows them to assess the chances of success of new or existing therapeutic strategies. “We love data,” she says, commenting on the new field of computational or data-driven medicine.
Professor Axel Pries, interim Chief Executive Officer of the BIH and Dean of Charité, is delighted at the new appointment: “With Claudia Langenberg we have succeeded in further expanding our pioneering role in computational medicine. All the research at the BIH and Charité will benefit from her vast experience in managing large international studies. Only in this way can we uncover the causes of major diseases and tackle them at the root.”
The architecture of metabolism
In recent years, Langenberg’s research has focused on uncovering genetic influences on “omics” data, especially on metabolites and proteins circulating in human blood. “Today, hundreds and thousands of these molecules can be detected and measured on a massive scale. A few years ago, this would have been impossible to imagine,” enthuses the scientist. In collaboration with colleagues from other research groups, her work has enabled the team to produce an atlas of the “architecture” of metabolism. “It is unusual for an epidemiologist to create knowledge for the next generation of biochemistry books,” admits Langenberg.
But what the scientist finds particularly fascinating is distinguishing between changes that contribute causally to the development of metabolic diseases and subtle measurement differences in healthy people. “Many of the responsible genes we found were already known,” explains Langenberg. “They cause serious ‘monogenic’ diseases, which are very rare and often already apparent in childhood. Evidently, the same genes also lead to metabolic changes in the general population. Our task now is to find out whether and how these changes manifest themselves clinically, because this will enable us to identify new targets for targeted therapies.” Her work therefore is fully in line with the BIH’s mission of turning research into health.
The role of genes in COVID-19
“I am very much looking forward to being in Berlin,” says Langenberg. “I not only have the enormous support of the translation hubs and core facilities of the BIH in evaluating large amounts of data, but I also have access to internationally renowned cooperation partners at the BIH and Charité.” Most recently, Langenberg worked with Professor Markus Ralser, Director of the Institute of Biochemistry at Charité, to analyze protein components in the blood of COVID-19 patients. “We were able to use the results of the Berlin study to identify genetic influences on COVID-19-relevant proteins in our Cambridge studies and quickly make them available to the scientific community,” explains Langenberg.
Langenberg has not yet cut all ties with her work in England, and continues to lead a team in Cambridge. “Some large, ongoing studies will not be completed for one or two years, and we are in the process of forming new international collaborations, which will then be managed from Berlin. It’s a win-win situation for both sides.”
Claudia Langenberg was born in Munich and studied medicine in Munster. After completing clinical training in Germany, she moved to the United Kingdom and the United Stated to obtain her master’s and PhD in epidemiology. In 2016, she completed specialist training in public health and the following year was appointed program leader at the MRC’s Epidemiology Unit at the University of Cambridge, where she had previously played a key role in discovering the genetic basis of metabolic diseases and risk factors and in setting up international consortia and meta-analyses. Claudia Langenberg has published over 250 scientific papers, many in prestigious journals, and is recognized as a Highly Cited Researcher by Thomson Reuters, a distinction received for being among the most cited researchers in her field. She has received numerous awards for her scientific work and served as editor in chief of “Generation Genome,” an annual report of the UK’s chief medical officer which contributed significantly to the reorganization of genomic medicine in the country’s National Health Service (NHS).
Claudia Langenberg has lived in Berlin with her husband and 6-year-old twin daughters since August.