V Scholar Archives - V Foundation

Robert Bowman, PhD

Abeloff V Scholar * (Tie for Top Rank)

Acute myeloid leukemia is an aggressive blood cancer. It affects thousands of people every year and often returns even after the newest targeted drugs. We have learned that, instead of dying, some cancer cells can “change their identity” to become a new blood cell type. These cells are called monocytes and they are able to escape therapy. This switch is like a costume change in a play: when the spotlight of treatment is on them, cancer cells put on a monocyte costume to hide. Later, when treatment eases, they can take off the disguise and return as cancer cells. We will test if these monocytes can turn back into cancer cells and cause disease to come back. We want to know how these cell changes happen and what helps them survive therapy. To answer these questions, we use new models that mimic patients’ cancer. We track how cancer cells looking at cell identity and genetic mutations. We also test new ways to block survival strategies, such as stopping the cells from becoming monocytes, in hopes of making current treatments work better and longer. By understanding and blocking the ways cancer escapes treatment, our goal is to develop strategies that keep patients in remission and improve survival.

William Hwang, MD, PhD

Abeloff V Scholar * (Tie for Top Rank)

Pancreatic cancer is one of the deadliest cancers. A condition called pancreatitis, which is prolonged inflammation of the pancreas, increases the risk of getting this cancer. For over 100 years, scientists have known that both pancreatitis and pancreatic cancer involve many nerves. But only recently have we started to learn that these nerves may actively cause pain, increase inflammation, and help cancer grow through direct interactions with cancer cells but also indirect effects on the immune system. However, we still do not fully understand how this works, and there are no treatments yet that target these harmful nerve-cancer interactions.Our research focuses on a type of nerve cell called a nociceptor. These nerves sense pain and use a protein called Nav1.8 to send signals. A new drug that blocks Nav1.8 was recently shown to be safe and helpful in reducing pain after surgery. In our project, we will test whether blocking Nav1.8 can also reduce pancreatic inflammation and slow cancer growth. We will also study how damaged nerves affect the immune system. Our early data suggests that injured nerves can change certain immune cells called macrophages, causing them to block T cells from attacking the tumor. Our overarching goal is to find new ways to prevent and treat pancreatic cancer by targeting the nerves that drive pain and disease. We hope these treatments will ease pain, stop cancer from forming or growing, and help patients live longer.

Amanda Dann, MD

Sarcomas are very rare types of cancer that develop from soft tissues- things like muscle, fat, and bone. Because they are so rare, they are often not caught early and have spread to other parts of the body by the time they are diagnosed. Once this happens, they can be very hard to treat. Our existing drugs often do not work very well to shrink or eliminate the cancer. My lab is working to develop new treatments for sarcoma, focused on targeting the nutrients these tumors need to grow and spread. Fast-growing tumors like sarcomas require more, and often different, nutrients than the normal tissues around them. This allows us to use drugs that target these pathways to slow down or shrink tumors while minimizing side effects to healthy tissue. We are able to measure how nutrients are used in patient tumors and using these findings to help refine treatment strategies. We have shown that sarcomas seem to rely heavily on certain nutrients- such as the amino acid glutamine, an important building block for many important cell functions. We are studying how new drugs that block the ability of cancer cells to use glutamine can be used to treat sarcoma. The goal of this work is to develop new treatments to help improve the lives of patients with sarcoma.

Thomas Hägglöf, PhD

The immune system protects us from infections, but it also plays an important role in fighting cancer. While many cancer treatments now focus on using the immune system to attack tumors, these treatments don’t work for everyone. To improve these therapies, we need to better understand how different immune cells behave inside tumors. Our research program focuses on a specific type of immune cell called the B cell. B cells are best known for making antibodies, but recently it was discovered that they are also found inside many types of tumors. Some B cells seem to help the body fight cancer, while others may actually help cancer grow. Right now, we don’t fully understand which B cells do what, or how. Our project will track how B cells enter tumors and how the tumor environment changes their behavior. We will use advanced tools in mice to follow B cells over time and test how certain stress signals, like low oxygen or changes in nutrients, affect how B cells grow and function. This work aims to discover better ways to boost the helpful B cells and block the harmful ones. By learning how to control these B cells, we hope to make immune-based cancer treatments work better for more people. Our ultimate goal is to use the immune system more effectively to help patients survive and thrive after a cancer diagnosis.

Haopeng Xiao, PhD

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.

Hannah Garner, PhD

Breast cancer is the second most deadly cancer for women in the U.S. and Canada. This is mainly because some kinds of breast cancer are aggressive and spread to other organs, which makes them very difficult to treat. However, new research has shown that some cells that are part of the immune system are very important in cancer spread, opening the door for new treatments. My previous work found that breast cancer changes the way that these immune cells develop and how they work. These changes help cancer spread. This project will study how this happens. We will use advanced technologies and laboratory models that recreate many aspects of breast cancer. This will allow us to understand how tumors change the immune system. We will study important cells of the immune system at different stages of their development to understand how they are changed by breast cancer. We will study how breast cancer changes the bone marrow, where these cells form. We will also study samples of cancer and immune cells collected from breast cancer patients at hospitals. This will let us link our lab findings with real-world cases to make sure that our research will help patients. Finally, our project will test new ways to stop the immune system from helping cancer spread. This may help prevent or treat the aggressive types of breast cancer and help more patients to survive this disease.

Valerie O’Brien, PhD

Stomach cancer is the fifth deadliest cancer in the world. Inflammation damages the stomach and causes harmful changes. First, the pre-cancerous cells start to show up. These cells cause the person’s body to make intestinal genes instead of stomach genes and can then lead to stomach cancer. However, we still have many questions about how and why pre-cancerous cells appear in the stomach in the first place. One important question is where the pre-cancerous cells come from. Scientists believe that some types of stomach cells can directly become pre-cancerous cells, but we do not fully understand which stomach cells can do this. Our research group looked at mice and humans with inflammation and damage in the stomach. We found that a stomach cell called a “pit cell” turned on intestinal genes. This meant that pit cells were pre-cancerous cells. This finding was surprising because scientists had already discovered that other cell types, not pit cells, become pre-cancerous. In our research project, we will learn more about why pre-cancerous pit cells appear. In the future we hope to develop drugs to stop these cells. We want to eventually develop ways to prevent pre-cancer from turning into cancer.

Emily Heikamp, MD, PhD

Acute myeloid leukemia (AML) is a deadly blood cancer that’s difficult to treat. Sometimes AML starts with a mistake in our cells. Think of DNA like a library of instruction books for your body. Imagine if pages from two different books accidentally got glued together—that’s what happens in AML when two different genes get stuck together to create a cancer-causing fusion protein. These fusion proteins take over the cell’s control system and make cancer cells grow without stopping.Our research team found that we can fight these cancer-causing fusion proteins by blocking other proteins that help them work. When we block these helper proteins, the cancer cells stop growing and start turning into normal white blood cells. We’ve shown that drugs blocking a helper protein called Menin can make cancer cells change back toward normal. Doctors are now testing these drugs in patients with AML. However, we’ll probably need to use several drugs together to completely cure this cancer.Our team also found two more important proteins called KAT6A and KAT7. These proteins help write the instructions that keep cancer cells growing. We’re studying how KAT6A and KAT7 work together with fusion proteins to cause leukemia. Understanding how these proteins cooperate to cause AML will help doctors create better treatments that cure more patients while causing fewer side effects.

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.

Jessica Tucker, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund

About 15% of human cancers are caused by viruses. By stopping these viruses, we can reduce cancer cases. Kaposi sarcoma and pleural effusion lymphoma (PEL) are cancers caused by a virus called KSHV. We don’t have enough treatments to stop KSHV from spreading.This project will study how a protein called Angiogenin (ANG) helps stop KSHV from spreading. As a secreted factor that promotes blood vessel formation, ANG can help tumors grow, but we discovered an important anti-viral activity of ANG in Kaposi sarcoma. We found that when KSHV becomes active in primary effusion lymphoma, it creates fragments of tRNA (a type of RNA) that block viral replication. ANG helps make these fragments, and without ANG, KSHV spreads more.The goals of this project are:To see how ANG stops KSHV from spreading.To understand how ANG and tRNA fragments affect protein production.This research could greatly help cancer patients, especially those with Kaposi sarcoma and pleural effusion lymphoma. By learning how ANG stops the KSHV virus, new medicines could be made to stop the virus and cancer from spreading, which may be applicable to treating other tumor-causing viruses. With better treatments, patients could live longer. Overall, this research could lead to new ways to treat virus-related cancers, giving patients hope for better outcomes and a better life.