Hyundai Hope Scholar Grant Allows for Advancements in Pediatric Cancer Research

How can advanced artificial intelligence tools expose hidden “poison exons” in cancer-related genes?

Backed by a $400,000, two-year Hyundai Hope Scholar Grant, Craig Forester, MD, PhD, and his team are pursuing a bold idea and stepping outside the conventional path of pediatric cancer research. Instead of producing new drugs that stop cancer cell growth that has already progressed, the lab focuses on targeting gene expression before the cancer cells arise.

The award is part of Hyundai Hope on Wheels’ long-standing commitment to pediatric cancer research. Since 1998, the nonprofit organization has supported scientists across the country through research funding and awareness campaigns. At Children’s Hospital Colorado alone, Hyundai Hope on Wheels has invested more than $6.1 million since 2006, including $800,000 in 2025.

This year’s support includes giving the $400,000 Hope Scholar Grant to Dr. Forester, who specializes in hematology and oncology at Children’s Colorado’s Center for Cancer and Blood Disorders. The highly competitive grant is reserved for physician-scientists conducting translational research that can move discoveries from the lab directly to patients.

Dr. Forester’s lab focuses on myelodysplastic syndromes (MDS), a rare bone marrow disorder that prevents the body from making healthy blood cells and puts children at risk for developing acute myeloid leukemia (AML). Although rare in children, MDS can be incredibly devastating, leading to a need for chronic transfusions, a risk of bleeding and infections or progression to leukemia. Dr. Forester’s work aims to stop these cells that are impaired by MDS from progressing to AML. He also hopes his work ultimately leads to more effective treatments.

“Limited funding often pushes researchers to play it safe,” Dr. Forester says. “This grant gives us the freedom to take a chance on a new direction that could really change how we treat these diseases.”

Harnessing poison exons: A new frontier in targeted gene therapy

The safer, well-worn route of research typically centers on drugs that block cancer-related proteins after they’ve already been made. Dr. Forester’s work, however, explores whether the problem can be stopped earlier, before the proteins even appear. His team specializes in RNA biology, which naturally led them to think about how cells process genetic instructions long before proteins come into play.

They turned their focus to RNA splicing, the process that turns immature RNA into its final, protein-making form. Buried within the genome are sequences that normally stay silent as they lie in non-expressed areas known as introns. However, if those sequences are included into mature RNA, they can act as red flags for the cell, indicating there is something wrong with a gene. These sequences are now nicknamed “poison exons” because they are poisonous to the gene and communicate to the cell to destroy it.

This sparked a new line of thinking in Dr. Forester’s work: Perhaps these sequences are far more widespread in the genome than researchers ever expected. To find out, the team launched a dual approach: testing in lab-grown cells while also harnessing an artificial intelligence supercomputer platform from ReviR Therapeutics. Using this tool, the team searches for hidden poison exons across the genome through the use of compounds known as splicing modulators. “We have found some interesting genes that we had no idea were holding sequences like these,” Dr. Forester says. “This is a new path forward in our lab in terms of targeting genes and gene expression, and it’s really cool for all of us.”

One gene studied by Dr. Forester is the Signal Transducer and Activator of Transcription 1 (STAT1) gene. If STAT1 could be turned off selectively, Dr. Forester believes the immune system could identify cancer cells more easily and eradicate them.

“These aren’t drugs that affect every gene in the body,” Dr. Forester says. “The treatment is tailored to one gene, so we could solve the issue without creating broader side effects and toxicities.”

The implications of this work also go beyond pediatric cancer. Since poison exons appear in many genes, the team believes this strategy could extend to autoimmune or inflammatory disorders as well.

“We think a lot of the great advances in science and medicine have come from these wild, new ideas,” Dr. Forester says. “This is a wonderful opportunity from Hyundai to not only allow us to push this idea forward but also to see how this idea could impact patients.”

Looking ahead, Dr. Forester sees his lab’s work as part of a broader shift in how science connects with medicine. “A little bit of the future of how to think about science is working on both sides of the axis — our knowledge, our experience with patients — and not thinking about biotechnology as something separate, but moving our two strengths together to push science forward faster,” he says.