Interview Ute Scholl
In February, BIH Johanna Quandt Professor Ute Scholl received the Paper of the Month. We have previously spoken with her about their research and the paper.
What is at the focus of your research?
My research group is dedicated to the genetics and pathophysiology of high blood pressure and endocrine tumors. One focus of our work is on primary hyperaldosteronism, the excess production of the adrenal hormone aldosterone, which leads to high blood pressure. As a postdoc and later on as the head of the research group, I was able to contribute to the discovery of ion channel mutations both in hormone-producing tumors of the adrenal gland as well as in familial forms of hyperaldosteronism. Curiosity and a love for research are what motivate me. In genetic studies, the greatest moment is when a new disease gene is identified, with the possibility of researching new physiological contexts, and ideally even with clinical applications. These rare and proudest moments provide motivation even in challenging times. One particular motivating factor is interacting with patients whose diseases we research.
What motivates you to perform this research?
In this study, we decoded the genetic cause for a hereditary high blood pressure syndrome. Called familial hyperaldosteronism type II, it causes excessive amounts of the blood pressure hormone aldosterone to be secreted, which usually leads to the development of high blood pressure in children or adolescents. This syndrome was first described in an Australian family 25 years ago, but the genetic cause remained unclear. However, we have now been able to identify mutations in the gene CLCN2, which codes for a chloride channel, in the Australian family and seven other families. This chloride channel is expressed in the aldosterone-producing cells of the adrenal gland. Opening the channel leads to a depolarization of the cell and the increased production of aldosterone. The mutations in patients with familial hyperaldosteronism lead to increased activity of the chloride channel and hence increased aldosterone production. In this study, we were able to demonstrate the significance of an anion channel for the aldosterone production of the adrenal gland for the first time.
Which cooperation partners have contributed to the publication? Who was significantly involved?
The publication is the result of many collaborations. Michael Stowasser and Richard Gordon’s group in Brisbane identified and characterized the large Australian family. At a conference, I asked Michael Stowasser if we could carry out additional genetic investigations on this family. This allowed us to identify CLCN2 as a candidate gene. For confirmation, we were able to use a cohort from Richard Lifton’s laboratory, who is now president of Rockefeller University. I worked as a postdoc in his laboratory at Yale University. The electrophysiological work was performed at Christoph Fahlke’s laboratory at Forschungszentrum Jülich, where Gabriel Stölting provided invaluable support. Murim Choi from Korea assisted us with the bioinformatic analysis. From my group, Julia Schewe and Anne Thiel lent their invaluable support. From BIH, Marieluise Kirchner and Philipp Mertins from the BIH Core Facility Proteomics provided their support.
What are the next steps planned for the project and what are the possible implications of your results for patients?
We want to better understand the functioning of the anion channels in the adrenal gland. For this purpose, we would like to carry out electrophysiological investigations, for example on a mouse model. We would also like to investigate the regulation of the channels. These findings will directly allow patients with a suspicion of familial hyperaldosteronism and their relatives to be tested for mutations in the gene CLCN2. The patients in our study responded to spironolactone, a drug used to treat primary hyperaldosteronism, such that this drug is available as a treatment option.