ERC Proof of Concept at TIGEM: Carmine Settembre Leads LEAD-ER to “Clean” Cells of Toxic Proteins

Naples, 30/06/2026 – The European Research Council (ERC) once again recognizes the research of the Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli: Carmine Settembre, Principal Investigator at the institute, has been awarded a €150,000 Proof of Concept (PoC) grant for LEAD-ER, a project dedicated to a new therapeutic approach focused on the removal of toxic proteins. With this new funding—aimed at translating previous research projects into practical applications—the total number of ERC grants received to date by TIGEM rises to 19, further confirming its international competitiveness.

At the core of the project is the endoplasmic reticulum (ER), a cellular organelle essential for protein synthesis, proper folding, and trafficking. Many genetic and age-related diseases are caused by the accumulation of defective proteins within the ER. These proteins are not efficiently cleared, leading to chronic cellular stress, tissue damage, and progressive organ deterioration.

To date, no therapies are able to target this mechanism directly; only symptomatic treatments are available. As part of his previous ERC-funded project (AUTO-SELECT), Dr. Settembre’s group helped elucidate the molecular mechanisms of ER-phagy, a form of selective autophagy that enables cells to eliminate misfolded proteins and maintain ER homeostasis.

This new project, LEAD-ER, represents the next step and aims to develop molecules capable of selectively enhancing this intracellular “cleaning” mechanism without interfering with other essential cellular processes. The new funding is intended to transform a basic scientific discovery into a therapeutic opportunity by developing and validating compounds that can selectively activate ER-phagy and demonstrate their effectiveness in cellular disease models.

If successful, this strategy could pave the way for a new class of therapies based on the selective degradation of proteins within specific cellular compartments, offering new treatment prospects for many diseases that currently lack effective cures.

As Carmine Settembre emphasizes: “We are working to transform the cell’s natural ‘cleaning’ system into a therapeutic tool capable of addressing the root cause of several diseases that currently have no cure.”