On May 14, 2025, the founders of FIGHT KIDS CANCER, including our president Patricia Blanc, will award Dr. Joshua Waterfall the FIGHT KIDS CANCER & St. Baldrick Foundation Innovation Award. This award, amounting to an exceptional 1 million euros, will enable Joshua and his team to explore new ideas and fundamental questions in pediatric oncology over four years. Originally from the United States, Joshua has a background in physics and fundamental biology. Since 2017, he has been developing innovative tools based on artificial intelligence at the Institut Curie, where he is a researcher, to analyze genes and immune cells interacting with tumors. The goal is to enhance the use of immunotherapy in childhood cancers to quickly propose anticancer vaccines or CAR-T therapies. To learn more about his unique and brilliant career, we met with him a few days before he received his award at the SIOP congress in Budapest.
Can you tell us about your background and your work against childhood cancer?
I obtained a PhD in theoretical physics at Cornell University. That was nearly 20 years ago, it feels like another life. Right after, I shifted to molecular biology, specifically the regulation of gene expression. I studied the fundamental mechanisms of gene regulation in different biological systems like flies, mice, and humans. There, I co-developed a new revolutionary sequencing approach. Then, I worked at the National Cancer Institute on genomics and epigenetics projects in the context of rare cancers in adults and children. In 2017, I joined the Institut Curie thanks to ambitious programs for recruiting young researchers. Since then, I have been co-affiliated with the translational research department within the INSERM Unit “Cancer, Heterogeneity, Instability, and Plasticity.” I helped create a research unit dedicated to pediatric cancers, led by Dr. Olivier Ayrault.
How did you come to work in pediatric oncology?
I came to pediatric oncology with dual expertise: the deregulation of gene expression in cancer and theoretical physics, which allows me to handle large datasets and develop complex models. I hadn’t planned to settle abroad—my wife and children are American—but I was immediately seduced by the freedom offered by the Institut Curie to explore the links between cancer and the immune system, particularly in pediatrics.
The specialty of my laboratory is to study in depth this interaction to understand the current obstacles to deploying immunotherapy in children. How are tumors recognized by immune cells? What distinguishes them from healthy tissues? How do genetic rearrangements in immune cells within tumors evolve over time and with treatments? These are still largely open questions. We answer them by analyzing patient data using artificial intelligence tools, particularly to discover new target tumor antigens. These advances are then put to use for patients through collaborations with clinicians or biotech companies.
How do you specifically work against childhood cancer?
My group is entirely computational. We do not directly analyze samples but exploit data from clinical and preclinical projects using databases. We collaborate closely with clinicians and other laboratories. A large part of our work involves molecular profiling of patient samples from the Institut Curie or other collaborators like Dr. Sophie Postel-Vinay, last year’s Innovation Award winner. International collaboration is essential in pediatric cancer research as it allows us to learn from as many patients and tumors as possible. We also benefit from data from mouse models or organoids, which complement our knowledge gained from patients.
How do you validate the obtained data?
Most pediatric cancers have few mutations, making them generally less detectable by the immune system. However, there are subtle modifications that can lead to the production of particular forms of mRNA in tumors, thus producing antigens of interest. My group is very skilled at detecting these RNAs specific to pediatric cancer, as well as the proteins and antigens derived from them, which can become therapeutic targets. To validate these targets, we consider many approaches, such as modifying patient T immune cells to recognize and attack tumor cells. This allows us to provide proof of our discoveries with in vitro and in vivo validations.
What ideas do you plan to explore with this award?
This award will be entirely dedicated to improving immunotherapy for children and adolescents with cancer. First, we want to identify new target antigens, particularly in cancers that are still difficult to treat, like Ewing’s sarcoma. Then, we want to fill an important gap in developmental immunology knowledge. We know how the immune system develops at birth and how it functions in adults. But we ignore what happens between 6 months and 18 years: for example, does puberty influence the immune response? Thanks to our collaborations with researchers collecting data on these periods, we will explore these new avenues to better stimulate immunity in young patients.
Specifically, what will you do with this funding?
We will recruit more PhD students to work on these questions. The Institut Curie has a new state-of-the-art proteomics platform essential for identifying antigens. Therefore, I do not need to invest in equipment or training. This award will allow us to fund many analyses of pediatric tumors that we could never have conducted without this support.
How is this childhood cancer award different from other funding?
The analyses we perform require advanced computer infrastructure and significant storage space. This award allows me to acquire all the necessary equipment. Moreover, 1 million euros over 4 years is a substantial amount, much more than most usual grants. This gives us the time and means to recruit, train, and work in depth. Finally, the freedom this award gives me to conduct my research is a precious mark of trust. It is, in a way, a dream come true.
An Innovation Award Unique in Its Kind
To realize this second FIGHT KIDS CANCER award, the St. Baldrick’s Foundation has once again joined forces. Their common goal is to support innovative and effective researchers in pediatric oncology, as cancer remains the leading cause of death by disease in France and Europe for children over one year old.
This unique innovation award is inspired by their shared values. Indeed, both encourage stepping off the beaten path, demonstrating true innovation and excellent scientific quality, and focusing on the potential impact for young patients.
The selection process was managed by the St. Baldrick’s Foundation. A selection committee composed of qualified experts in pediatric oncology research had the very difficult task of choosing a winner among talented early or mid-career scientists with international collaboration experience.
To learn more about this award, visit the Fight Kids Cancer website by clicking here.