Ton Rabelink receives ERC Advanced Grant for research on metabolism in kidney repair

Professor Ton Rabelink, Netherlands Node Director

Prof. Ton Rabelink, reNEW Leiden PI, has been awarded a prestigious ERC Advanced Grant worth 2.5 million euros. With the grant, Rabelink will further his research on tissue repair after kidney injury. The goal is to gain new insights into the role that metabolism plays in this process. Results of the research can be used to develop new therapies that promote kidney tissue repair.

Rabelink is delighted with the allocation: “This grant enables us to take our ongoing research on metabolism in kidney repair to the next level. It will thereby help us better understand the role of this process and make it possible to repair kidney damage in the future.”

Chronic kidney disease: a global problem
Worldwide, 850 million people suffer from chronic kidney disease. The kidneys of these patients are permanently damaged, meaning they can no longer fulfil their role as waste filters of the body. Only one real treatment is currently available for patients with severe kidney disease: kidney transplantation. However, there is a large shortage of donor organs for this. In the absence of such donor kidney, patients depend on dialysis. This intensive treatment is not curative though and has many side effects.

Metabolism as key to success
Although kidneys cannot repair themselves from long-term damage, they can recover from acute damage in some cases. This does not always happen though, and the reasons for this inconsistency are not well understood. Rabelink’s group aims to gain more knowledge on this process. In this light, the group has recently shown that metabolism of kidney cells plays an important role in repair. Rabelink: “The citric acid cycle – part of metabolism – is essential for recovery. If it does not work properly, cells do not produce enough energy and building materials needed to repair damaged tissue.” Nevertheless, a lot remains unknown about the role of metabolism in kidney repair beyond the citric acid cycle. SPARK, as the new project is called, will now further investigate this.

State-of-the-art technology
To this end, various changes in kidney tissue after damage will be mapped in collaboration with the LUMC Center for Proteomics and Metabolomics. “This is only possible thanks to highly advanced technology developed at LUMC,” Rabelink says. “With this we can study slices of kidney tissue and obtain an overview not only of the entire metabolism in this slice, but also of the consequences that the metabolism has on DNA and RNA. We do this in detail, at the level of a single cell. Using complex algorithms, we can then integrate the gigantic amount of data this yields. This gives us a complete overview of changes in kidney cells during tissue repair. Unique not only in the Netherlands, but in the whole world.”

Dot on the horizon
The study will provide new knowledge about how metabolism affects tissue repair in general and the specific metabolic processes that play an important role in kidney repair. Rabelink concludes: “If we influence these processes with novel treatments, we can repair acute kidney damage better and thus prevent chronic kidney disease. That’s what we’re doing it for.”

Reprogrammed neurons may fool you!

Associate Professor Agnete Kirkeby, from reNEW Copenhagen, has published the paper Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, in Stem Cell Reports.