Research Spotlight: Jean Bertoldo

But researchers like Dr. Jean Bertoldo are working to change that. A 2024 ChadTough Defeat DIPG Foundation New Investigator recipient, Dr. Bertoldo is leading a bold research effort at Children’s Cancer Institute aimed at developing an entirely new kind of therapy—one that directly targets the underlying cause of DIPG tumor growth.
His work represents a shift in how scientists think about treating this disease.

Targeting What Drives the Tumor
At the center of Dr. Bertoldo’s research is a genetic mutation known as H3K27M—widely recognized as a primary driver of DIPG. While scientists have understood its importance for years, attempts to target it with drugs have been unsuccessful. Until now.

Using advanced tools in chemoproteomics and artificial intelligence, Dr. Bertoldo has developed a promising new agent called JNSY1. Unlike traditional therapies, JNSY1 is designed to directly interact with, and disrupt, the mutation itself.

“I’ve already shown that this agent can bind to this mutation, restore normal gene function, and selectively kill DIPG cells,” Dr. Bertoldo explains.

With support from ChadTough Defeat DIPG Foundation, his team is now working to advance JNSY1 into a drug candidate that could eventually move into clinical trials. If successful, it would represent a “first-in-class” therapy, an entirely new category of drug for DIPG.

A Breakthrough Approach
What makes JNSY1 especially exciting is not just what it targets, but how it works. Recent findings have shown that JNSY1 acts as the first known “H3 degrader,” selectively removing the abnormal H3K27M protein without disrupting healthy cellular function. By doing so, it triggers a cascade of effects inside the tumor.

In simple terms: it doesn’t just stop one problem—it begins to shut down multiple pathways that allow the tumor to grow. This includes reactivating critical tumor-suppressing mechanisms and reducing the activity of several key drivers of DIPG, including MYC and PDGFRA. Early studies have also shown that the drug can cross the blood-brain barrier, reduce tumor burden, and extend survival in preclinical models. It’s a powerful one-two punch—targeting the root cause while also weakening the tumor’s broader support system.

Dr. Bertoldo’s approach could have implications far beyond a single disease. As he explains, “This method can be applied to other genetic targets in pediatric cancers,” meaning this work has the potential to unlock new treatment strategies not only for DIPG, but for other childhood cancers that have historically lacked effective therapies.

Originally from Brazil, Dr. Bertoldo brings a global perspective and deep expertise in chemical biology and drug design. Before joining Children’s Cancer Institute in Australia, he trained at leading institutions across Europe and developed pioneering therapies in other cancer types.

Through its New Investigator Grant program, ChadTough Defeat DIPG Foundation supports researchers like Dr. Bertoldo at critical stages in their careers, fueling innovative ideas that have the potential to reshape the field.

Because progress in DIPG doesn’t come from one breakthrough alone. It comes from bold thinking, new approaches, and the belief that even the most challenging diseases can be understood—and eventually, overcome.