Published on 03.01.2020
Matias Simons studied medicine in Heidelberg, Germany and then moved into nephrology after performing his MD thesis in renal research. “During this time I realized that it is really difficult to handle both research and clinical work simultaneously, said Matias Simons. Therefore I decided to focus only on research.”
“In my first post-doc, I discovered a link between cystic renal diseases and a pathway that commands planar polarity in epithelia,” said Matias Simons. Mutations of a protein called inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. They showed that inversin acts as a molecular switch between different Wnt signaling cascades.
He then used Drosophila in his second post-doc and with his own research team to study planar polarity in more detail. In 2013, he heard about the creation of a new institute in Paris dedicated to genetic diseases: Imagine Institute. ‘It was a real opportunity to bring back my research to genetic diseases, he says. The institute was on the site of Necker, a famous and unique place in the world of pediatric diseases, and it brings together specialists from various organs - kidney, bones, brain… - all working on genetic diseases. The critical mass of scientists dedicated to rare genetic diseases was very appealing”.
Apart from using Drosophila as a tool for the functional validation of candidate genes, he also collaborated with Prof. Corinne Antignac, a physician and researcher specialized in rare kidney diseases at Imagine institute. He got involved in diagnostic activities and identified many patients with a mutation in a gene called cubilin (or CUBN) leading to loss of proteins into the urine or “proteinuria”. Proteinuria is usually associated with a bad prognosis for the kidney. However, in this particular case the proteinuria does not lead to any renal pathology or dysfunction, which is a real surprise. Moreover, by population-based studies they found that CUBN variants associated with a potentially improved renal function in cohorts of patients with chronic kidney disease. Therefore, Simons suggested that inhibition of cubilin-mediated protein uptake in the proximal tubules of the nephron could be a renoprotective strategy.
“My idea is that CUBN variants may have persisted in human evolution to protect the kidneys”. The ERC grant will allow him to pursue his research on this precise discovery. And soon he will leave Institut Imagine in order to spread the Imagine’s spirit at the University of Heidelberg in Germany, but he will continue to collaborate with researchers at Imagine.