California Archives - V Foundation

Yun Li, MD, PhD

This project aims to find better treatments for advanced prostate cancer. This type of cancer is very hard to treat once it spreads. Many treatments, including immunotherapy (which helps the body fight cancer), have not worked well for these patients. One reason is that prostate cancer can “hide” from the immune system.Our research focuses on combining two types of treatment: radiation and immunotherapy. Radiation can damage cancer cells, but it can also help “wake up” the immune system. When cancer cells are hit by radiation, they send out signals that make them easier for the immune system to see. In this project, we use a newer type of radiation that travels through the bloodstream and can reach cancer cells throughout the body. Unlike standard radiation that targets only one spot, this approach can find and treat cancer wherever it has spread and may help activate immune cells across the whole body. After this, we give a newer form of immunotherapy that helps immune cells find and attack the cancer more directly. You can think of radiation as turning on a signal, and immunotherapy as helping the immune system follow that signal to the tumor. We will study blood and tumor samples over time to learn how the immune system responds to this combination. Our goal is to find the best timing and way to give these treatments, so they work better together. This research could lead to more effective and longer-lasting treatments for patients with advanced prostate cancer and may help improve care for other cancers as well.

Yali Dou, PhD

Acute myeloid leukemia (AML) is a fast-growing blood cancer. It is hard to treat, and it often comes back even stronger after treatment. One reason AML is so difficult to fight is that cancer cells take control of the normal systems that turn genes on and off. These systems are called epigenetic controls. When they do not work properly, leukemia cells can grow quickly, avoid treatment, and push out healthy blood cells.This research focuses on one of these gene regulators called MLL1. MLL1 helps turn on important genes in blood cells. In some leukemias, the MLL1 gene is broken or rearranged. However, we now know that a small group of adult AML patients have extra copies of the MLL1 gene. These patients often develop AML after having other blood disorders or after receiving chemotherapy. Sadly, they usually do not respond well to current treatments. Right now, there are no therapies made specifically for this group.Our study uses new knowledge about how MLL1 helps cancer cells grow. We will test whether leukemia with extra or altered MLL1 has weak points that new drugs can target. We will also explore ways to directly target MLL1. Our goal is to develop more personalized treatments that help patients live longer and healthier lives.

Frank B. Furnari, PhD

A brain cancer called glioblastoma is one of the deadliest cancers. Even with surgery, radiation, and chemotherapy, most patients only live about 15 months. The biggest problem is that the cancer almost always comes back. Scientists are still learning why this happens. Some cancer cells, called “persister cells,” can survive radiation therapy by going into a kind of hibernation. When treatment stops, these cells wake up and start growing again, causing the tumor to return. Think of it like weeds in a garden. If you don’t remove all the roots, the weeds grow back.Our research discovered that a protein called BRD2 helps these persister cells survive radiation. When we remove BRD2 from cancer cells in the lab, they die from radiation. But when we use drugs to block BRD2, some cells still survive. They find other ways to stay alive.We’re now testing drug combinations. These drugs block both BRD2 and the backup routes cells use to survive, stopping cancer cells from returning after radiation. Another problem is getting drugs into the brain. The brain has a natural wall that blocks most medicines. We’re creating tiny particles that can carry drugs past this wall. Think of them as special delivery trucks that know a secret path into the brain. If this works, we could have new treatments that stop brain tumors from returning after radiation. This would give patients more time with their families, changing this deadly cancer into a disease we can control.

Haopeng Xiao, PhD

In honor of Ariel Ungerleider Kelley & Shoshana Ungerleider and in memory of Steven Ungerleider, V Foundation 2026 Sonoma Epicurean

Metabolism is how cells use nutrients to make energy and build the molecules they need to live. Cancer cells, unlike healthy cells, can change these processes. This rewiring helps them grow faster, resist stress, and avoid death. Learning how this happens may lead to new treatments.Our lab uses data-driven tools to study cancer metabolism. One of our main methods is mass spectrometry. This tool measures thousands of proteins and metabolites, and these molecules are the building blocks of metabolism. By measuring them in cancer, we can create a clear picture of how cancer cells use their metabolism to their advantage. These large datasets also allow us to use machine learning to find hidden patterns and weak points that cancer depends on.With this approach, we found a protein that controls the levels of cysteine, an amino acid that cancer cells need to grow and survive. The protein works by sensing and adjusting cysteine levels in cells. We are now testing if it can be a new drug target to kill cancer cells. In the future, we will use similar methods to find more hidden rules that let tumors survive. Our goal is to turn these findings into better cancer treatments that directly target cancer’s unique metabolic needs.

Jonathan Chou, MD, PhD

Bladder cancer is the 5th most common cancer in the United States and causes about 17,000 deaths each year. When it spreads to other parts of the body, patients usually live less than two years. In the past few years, a new type of treatment called antibody drug conjugates (ADCs) has changed how bladder cancer is treated. One of these drugs, enfortumab vedotin (EV), targets a protein on bladder cancer cells called NECTIN4. When EV is used alone or with immunotherapy, this new therapy can shrink tumors in nearly 70% of patients at first. Sadly, most patients with bladder cancer become resistant after about a year, which means that the cancer stops responding to the treatment.We first thought this resistance might happen because tumors lose expression of the target NECTIN4. But when we looked at tissue samples from patients whose cancer stopped responding, we found most resistant tumors still had it. This project will explore other reasons why resistance happens and how to delay or reverse it. This includes looking at how the drug is processed inside cells, how it gets broken down, and how immune cells around the tumor may play a role. We will study both cancer cells and patient samples to see what changes occur as resistance develops. We will also test new drug designs, try other ways of targeting NECTIN4, and build new lab models from patients whose cancers are resistant. This work could lead to better treatments not only for bladder cancer but also for other cancers treated with ADCs.

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

Funded by the Stuart Scott Memorial Cancer Research Fund

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.

Hanna Mikkola, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Constellation Gold Network Distributors

Children with Down syndrome have a higher chance of getting blood cancer called leukemia. Many babies are born with a condition called transient abnormal myelopoiesis (TAM). TAM starts before birth and causes too many immature blood cells to grow. In most babies, TAM goes away on its own. But in some, it can be very serious or later turn into leukemia. Right now, doctors do not know why this happens or how to tell which babies are at risk.In this study, we will use new tools to look at single blood cells to learn more about how TAM starts, how it changes into leukemia, and why treatments sometimes stop working. We will study blood and bone marrow samples from children at different stages of the disease, as well as from pregnancies with Down syndrome, to find out when and where the first changes begin.Our goal is to find better ways to predict which babies with Down syndrome will get leukemia and to develop safer, more effective treatments. This work could improve survival and quality of life for children with Down syndrome and their families.

S. John Liu, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Diffuse midline glioma is a deadly brain tumor that affects children. Radiation is the main treatment, since surgery and chemotherapy do not work well. New drugs are being tested, but they are not proven yet. To find better options, we built a new method that combines gene disruption with detailed study of brain tumors. This lets us test the role of many genes in new ways. We found genes that may help tumors respond better to treatment. Now, we will study how these genes work. Our goal is to discover new treatment combinations that can help children with glioma live longer and healthier lives.

Christina Curtis, PhD

Funded with support from John and Debbie Mastriani

Why do some people get certain types of cancer, while others don’t? For some cancers, we know that inherited genes play a role. But for many, it’s still a mystery. One reason is that cancer is very complex and we don’t fully understand how a person’s genetic makeup and immune system affects their risk.In our recent research, we found something surprising. We discovered that both a person’s genes and their immune system work together to influence which type of cancer they might develop. This includes hard-to-treat types like HER2+ and ER+ breast cancer, which can come back many years after treatment.Some early changes in a tumor’s DNA can act like a warning signal, helping the immune system find and destroy these abnormal cells before they grow. But if the tumor hides from the immune system, it can become more dangerous. That’s why it’s so important to find and treat these cancers early.Our work helps to explain the role of genetic variation in cancer, even when no single gene seems to be responsible. It also points to new ways to determine who is at risk and to create treatments that are personalized—based on each person’s genes and immune system. We’re working to turn these discoveries into better tools to predict, prevent, and treat cancer more effectively.