ERC Proof of Concept 2026: Two Grants Awarded to San Raffaele for Research on Polycystic Kidney Disease and Liver Cancer

The European Research Council (ERC) has announced the winners of the 2026 Proof of Concept (PoC) call. Among this year’s awardees are:

• Alessandra Boletta, Group Leader of the Cystic Kidney Disorders Unit at IRCCS Ospedale San Raffaele;
• Matteo Iannacone, Professor of General Pathology at Vita-Salute San Raffaele University, Director of the Institute of Immunology and Infectious Diseases, and Group Leader of the Dynamics of Immune Responses Unit at IRCCS Ospedale San Raffaele.

The two grants will support the development of innovative therapeutic strategies for polycystic kidney disease and liver cancer, helping translate discoveries from basic research into potential clinical applications.

The ERC Proof of Concept programme is designed to help researchers transform ERC-funded discoveries into innovations with real-world impact, bridging the gap between frontier research and practical applications. It is open exclusively to researchers who have already received an ERC grant and aims to support the development of the innovation potential of their scientific findings.

Rather than funding the original research itself, the PoC programme finances additional activities needed to assess and validate the commercial or societal potential of discoveries generated through ERC projects.

Within this framework, Dr. Boletta and Professor Iannacone—both recipients of an ERC Advanced Grant in 2023—have each been awarded an additional ERC Proof of Concept Grant worth €150,000 for a period of 18 months.

In the first funding round of 2026, the ERC evaluated 554 proposals, selecting 182 projects for funding, with a total budget of €27.3 million. Of these, 37% support research in the Life Sciences. Italy secured 18 ERC Proof of Concept grants, including the two awarded to Dr. Boletta and Professor Iannacone.

These new awards add to the long list of achievements by researchers at IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, bringing the total number of ERC-funded projects at the two institutions to 39 since the establishment of the European Research Council in 2007.

Polycystic Kidney Disease (PKD) is the most common inherited kidney disorder and one of the leading causes of kidney failure. It is characterized by the progressive transformation of the kidney's microscopic tubules into fluid-filled cysts. As these cysts slowly but continuously enlarge, kidney function gradually declines.

PKD belongs to a group of disorders known as ciliopathies, which are caused by defects in the primary cilia—tiny hair-like structures on the surface of cells that act as sensory "antennas," allowing cells to detect and respond to their environment.

Dr. Boletta's research team has uncovered a previously unknown function of primary cilia in regulating cellular metabolism. Their work demonstrated that these structures can sense glutamine, an important nutrient, and regulate energy production within mitochondria, the cell's energy-producing organelles.

Through the QtCilia project, which received an ERC Advanced Grant in 2023, the team identified the enzyme asparagine synthetase (ASNS) as a key regulator of this process and showed that disabling the enzyme slows disease progression in animal models.

The new ERC Proof of Concept project, "Targeting Glutamine (Q) Metabolism in the Renal Ciliopathies" (QrCiliopathies), developed in collaboration with the Centre for Drug Design and Discovery (CD3) at KU Leuven, will support the development and testing of novel drugs capable of inhibiting ASNS in cellular and animal models of PKD.

By exploiting this newly identified metabolic vulnerability, the project could pave the way for new treatments not only for polycystic kidney disease but also for other ciliopathies.

"This project represents an exciting and important milestone for me. I have been working on cystic kidney diseases for nearly 30 years.

While the ERC Advanced Grant provided major international recognition and substantial funding to pursue fundamental research into inherited kidney diseases, this new project moves us one step closer to treatment. It brings us back to our primary mission: providing answers for patients. It is yet another demonstration that outstanding basic research generates major advances in translational medicine.

This perfectly reflects our hospital's motto: 'There is no treatment without research.' Without understanding the molecular basis of disease, it is impossible to develop effective therapies. There are no shortcuts. Anyone claiming otherwise is either mistaken or bound to fail," says Dr. Boletta.

Professor Iannacone's ERC Proof of Concept project, "Liver mRNA-based Immunotherapies" (LiveRNA), will support the development of a new generation of mRNA-based immunotherapies for the treatment of liver cancer.

Although mRNA technologies became widely known through vaccines, their therapeutic potential extends far beyond infectious diseases.

LiveRNA builds on more than 15 years of research that revealed how the liver can induce immune dysfunction, limiting the immune system's ability to control cancer, while also identifying strategies capable of restoring effective immune responses.

The project's goal is to use mRNA technology to selectively deliver immune instructions directly to the liver, reactivating both innate and adaptive immunity and restoring the body's natural ability to recognize and eliminate cancer cells.

This latest award represents the culmination of a long-term research programme supported by the ERC for over 15 years through a Starting Grant, a Consolidator Grant, an Advanced Grant, and now three Proof of Concept Grants.

This sustained support enabled Professor Iannacone's team to discover how immune cells become dysfunctional within the liver and to identify strategies capable of restoring their activity.

The team's work has also established the liver as a model for understanding how immune responses are organized within tissues and how the local tissue environment shapes immune function in chronic diseases and cancer.

LiveRNA combines two complementary strategies:

• one reactivates innate immune recognition within tumour cells;
• the other restores the function of anti-tumour T cells.

Together, these technologies aim to convert cancers that are currently resistant to immunotherapy into tumours that the immune system can effectively control.

Beyond liver cancer, this work could establish a broader platform for developing mRNA-based therapies for other cancers and chronic diseases.

Professor Iannacone commented:

"Receiving this ERC Proof of Concept Grant is particularly meaningful because it represents the final step in a scientific journey that began with my ERC Starting Grant in 2011.

Over the past 15 years, ERC support through a Starting Grant, a Consolidator Grant, an Advanced Grant, and now three Proof of Concept Grants has allowed us to pursue ambitious, curiosity-driven research into how immune responses are organized within tissues and how they fail in chronic diseases and cancer.

What makes this award especially rewarding is that it completes the circle: discoveries originally made through fundamental immunology research are now being translated into a potential therapeutic strategy for patients with liver cancer.

In many ways, LiveRNA demonstrates the unique value of long-term investment in frontier research and shows how sustained support for basic science can generate entirely new concepts and ultimately create tangible opportunities for clinical innovation.

This recognition also belongs to the many students, postdoctoral fellows, and collaborators who have contributed to this work over the years."