2025 Archives - V Foundation

Richard Voit, MD, PhD

Childhood AML is a devastating blood cancer with high rates of treatment failure and relapse. Some types of AML are especially difficult to cure because they have high levels of a protein called MECOM. These AMLs reawaken signals that are normally only active in healthy blood stem cells. We know that high levels of MECOM are bad in AML, but targeted drugs have not been developed. In this proposal, we will use cutting edge technologies to test for weak spots in the MECOM protein itself. This will allow us to develop targeted drugs that can attack those weak spots. In this way, we aim to develop new medications to treat and cure childhood AML.

Tomohiro Aoki, MD, PhD

Lymphoma is one of the most common blood cancers. Treatments have helped many people, but for some, the cancer comes back after treatment. When that happens, it can be harder to treat. New research shows that finding shared targets in different types of lymphoma could lead to better treatments.

Cancer does not grow alone. It is surrounded by other cells called “stromal cells.” These stromal cells can sometimes help the cancer grow or resist treatment. But we still do not know exactly how they work or how many different types there are. In this project, we will use special tools to study these cells one by one. One tool is called single-cell sequencing, and another is called the CosMx Spatial Molecular Imager. These tools help us look closely at tumor cells and stromal cells to see how they work together.

We will also use lab models made from real patient samples. These models will help us watch how cancer and stromal cells behave together, both in lab dishes and in mice. We can then test new treatments that block the bad interactions between these cells. Lastly, we will use gene-editing technology to learn how cancer cells escape the immune system and resist treatment.

By better understanding how stromal cells support lymphoma, we hope to find new ways to treat the disease and help more people survive.

Jared Mayers, MD, PhD

Our bodies are home to trillions of tiny living things called bacteria. A growing amount of research shows that these bacteria can play a role in how cancer starts and grows. Most scientists have focused on this connection in the gut, which is packed with bacteria. It might also be true for the lungs, but this is much harder to study because the lungs have far fewer bacteria. Right now, we can only identify which bacteria are there. To learn how these lung bacteria might affect cancer, we need to understand what they are actually doing. Unfortunately, our current tools are not sensitive enough to show us. We are creating two new ways to look at lung bacteria in cancer tissue from patients. These tools will let us see not only which bacteria are there, but more importantly, which of their genes are turned on. A gene that is “turned on” can tell us what a bacterium is doing. This will help us form new ideas about how they could be involved in lung cancer. This work will provide the first detailed picture of how bacteria might be involved in lung cancer. Understanding their role could lead to new tests to find lung cancer earlier or to identify people who are at a higher risk. It could also help us discover new ways to prevent lung cancer. We might even be able to design personalized treatments that change a person’s unique mix of bacteria to help fight cancer.

John Hickey, PhD

T cell therapy uses a person’s own immune cells to fight cancer. It has cured some blood cancers, like leukemia and lymphoma. But it does not work well for solid tumors in organs such as the lung, pancreas, or colon. My research asks why—and how to fix it.One problem is how the cells are grown before they go back into the body. Today, most labs use a “one size fits all” recipe. That recipe helps T cells multiply, but it does not train them for the tough job inside a solid tumor. Another problem is that people are different. Age, sex, and health history can change how T cells grow and work. A third gap is knowledge: we do not fully know what these cells do once they enter a tumor.To solve these challenges, I am building new tools to fine-tune how T cells are prepared and to track how they work in tumors. I will test many preparation methods at the same time and combine advanced imaging and AI to find the best recipes that make T cells that get into tumors, last longer, and fight cancer cells more effectively. The goal is simple: smarter, stronger T cell treatments for solid tumors. If successful, this work will guide doctors to match the right recipe to each patient and cancer. That could mean better responses, fewer side effects, and longer lives.

Mitchell Fane, PhD

Melanoma is the deadliest type of skin cancer because it can spread from the skin to organs like the lungs and liver. This spreading, called metastasis, can cause organ failure and is the main reason people die from melanoma. Some melanoma cells can hide in these organs in a quiet or dormant state for decades. While dormant, the cancer is not growing and cannot be found or treated. Later, these hidden cells can wake up, grow quickly, and form deadly tumors. Current treatments, including immunotherapy (which helps the body’s immune system fight cancer), often fail once melanoma returns.Most research uses young mice to study how melanoma spreads and to test treatments. But melanoma mostly affects older adults. The average age of diagnosis is 65 years-old. This mismatch means many treatments may not reflect how melanoma acts in older patients, which makes up most of the melanoma cases.Our research shows that age plays a key role in melanoma spreading. In young mice, melanoma cells that reach the lungs and liver often stay dormant. In older mice, the same cells wake up and form aggressive tumors. We show that this happens because the immune system gets weaker with age. We found that aging raises certain proteins that block the immune system from stopping cancer. Increasing these proteins in young mice causes cells to wake up and promotes aggressive cancer.This project will test if blocking these proteins can stop melanoma from coming back, spreading, and help current treatments work better.

Michael Wilson, PhD

In 2025, about 69,120 people in the United States will be diagnosed with uterine cancer. Over the past thirty years, this number has steadily grown—especially among young women. When caught early, uterine cancer can often be cured by removing the uterus. However, this is not a good option for younger women who still want to have children. That is why our lab is focused on learning more about uterine cancer and finding new treatment options for these young women. From studying large groups of patients, we found that a gene called KMT2D is mutated more often in tumors from younger women than in those from older women. Using mouse models, we discovered that tumors with KMT2D mutations tend to grow faster and act more aggressively. We compared these findings with patient data and believe tumors with this mutation might respond well to certain drugs. One group of these drugs is called CDK-inhibitors, which are already used to treat breast cancer. Our research suggests these drugs might also work against uterine cancers with KMT2D mutations. So, in this study, we will use our mouse models to learn how KMT2D helps tumors grow, test new drugs on these mice, and compare our results with patient data to see if these treatments could be viable. We have brought together a team of scientists, doctors, and cancer survivors to do this work. If successful, this work could open the door to new, life-changing treatments for young women with uterine cancer.

Xueqin Sun, PhD

Glioblastoma (GBM) is one of the most common and deadly brain cancers, and survival rates have barely improved in decades. In our research, we found a hidden weakness in GBM tumors that could lead to a new treatment. Think of p53 as the body’s security guard that protects against cancer. But in about 71% of GBM tumors, another protein called BRD8 locks up this guard so it can’t do its job. We discovered a way to break apart BRD8 with new drugs, which could free p53 and let it fight the cancer again. We will test this approach using lab-grown GBM cells and mini-brain tumor models created from patient samples. Our approach could help develop new therapeutic strategies for patients facing this devastating disease.

Tikvah Hayes, PhD

Lung cancer is the leading cause of cancer-related deaths worldwide. The most common type is called non-small cell lung cancer (NSCLC), which consists mostly of adenocarcinomas and squamous cell carcinomas. In about 15–20% of adenocarcinoma cases, the cancer is caused by changes in a gene called EGFR. This gene normally makes a protein that helps cells grow and divide in a healthy way. But when EGFR is changed, or mutated, it can send the wrong signals, causing cells to grow out of control and form cancers. There are already drugs that target some EGFR mutations. These medicines, called EGFR tyrosine kinase inhibitors, can be very effective for certain patients. However, they only work for specific mutations in one part of the EGFR protein. Other mutations, found in a different part of the protein called the extracellular domain (the section that sits outside the cell), don’t respond to any of the current treatments. These mutations are less common, but they still affect many people with lung cancer. Unfortunately, scientists know far less about them. Our project aims to change that. Using human lung cells and advanced 3D models called organoids, we are studying how these rare EGFR mutations cause cancer, how they interact with other cancer genes, and why today’s drugs don’t work. We are also using new genetic tools to search for weak spots in these cancer cells that could become targets for future medicines. By uncovering how these overlooked mutations drive cancer, we hope to open the door to better treatments for patients with lung cancer.

Jared Rowe, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Neuroblastoma is the most common cancer in babies. It can act in surprising ways. Some forms grow quickly and are very hard to treat. Others, especially in babies under 18 months old, can shrink or even disappear without treatment. Doctors do not fully understand why this happens, but the immune system may play a key role. One type of immune cell, called the CD8⁺ T cell, is especially good at finding and killing cancer cells.This project will study whether the immune system in babies works differently from that of older children or adults, and whether these differences can explain why some tumors go away on their own. Baby T cells are often thought of as immature, but new research shows they can grow faster, work more efficiently, and resist “burning out” better than adult T cells.In our early work, we trained baby T cells to recognize neuroblastoma cells. They were better at killing these cancer cells than adult T cells. We also found that baby T cells rely on a nutrient called pyruvate for energy and function. They process pyruvate in a special way using an enzyme called GPT.We will test whether this unique metabolism is the reason for their strong performance. We will also see how the tumor environment changes T cell metabolism, and whether changing the way T cells use pyruvate can make them even better at fighting cancer.We will use umbilical cord blood as a safe, widely available source of baby T cells. If this approach works, it could lead to new cancer treatments designed for children. The goal is to make these treatments safer, more effective, and take advantage of the natural strengths of the infant immune system.

Craig Byersdorfer, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Treatment of childhood cancers is tough. However, our recent success rate has improved. This is because of our ability to redirect the immune system to attack cancer cells. These advances have resulted in many cures. However, success has not been perfect. Relapses continue. Further, we know the risk of cancer increases when immune cells go away. Or when the cells do not function properly. It has also become clear that knowing the energy pathways used by immune cells is vital. This knowledge can help predict how well our treatment will work. However, it has been challenging to reprogram immune cells. Many treatments restrict cell growth. Or limit cell number. In our studies, we discovered a new way to reprogram cancer-targeting immune cells. Our method improves their anti-cancer properties. Without limiting cell growth. Or function. We believe that these beneficial changes will increase the chance of a successful treatment. Especially when immune cells are given back to children with high-risk leukemia. In the current application, we will test our new treatment in many ways. We will test immune cells recovered from leukemia patients. We will compare our approach to similar treatment strategies. We will define whether immune cells need to stick around. And, we will extend our studies into ‘real world scenarios’. Together, we hope to bring our treatment to patients with high-risk leukemia. Within the next five years.