Designed to identify, retain and further the careers of talented young investigators. Provides funds directly to scientists developing their own independent laboratory research projects. These grants enable talented young scientists to establish their laboratories and gain a competitive edge necessary to earn additional funding from other sources. The V Scholars determine how to best use the funds in their research projects. The grants are $200,000, two-year commitments.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Our goal is to find better ways to treat children diagnosed with a blood cancer called acute myeloid leukemia (AML). AML is a devastating illness that affects around 500 kids in the United States every year. While many children respond well to current treatments, some don’t, and their cancer comes back, which can be very hard to treat. Our work focusses on a specific group of cells within the blood cancers called leukemia stem cells (LSCs). These cells can survive through treatment and cause the cancer to come back. So, we need new treatments that can specifically kill these LSCs. We’ve discovered that these LSCs rely on molecules called polyamines to survive. By decreasing the levels of polyamines using drugs, we can stop the LSCs from making proteins they need to stay alive. Our research suggests that a protein called eIF5A plays a big role in this process. Now, we want to test if drugs that block polyamine metabolism can stop AML from growing in models that mimic what happens in patients. We also want to understand exactly how eIF5A helps the cancer cells survive. If our experiments are successful, it could lead to new treatments for children with AML that have the potential to improve the outcomes for these children.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer
Despite significant advances in the treatment of pediatric cancer, leukemia remains the second leading cause of cancer related death in children. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that affects both children and adults. When T-ALL does not respond to chemotherapy or returns after initial treatment (relapses), there are few treatment options. New treatments are needed for T-ALL. The way cancer cells use energy or develop building blocks for growth is different from normal cells. We are working to understand how these energy and building processes within T-ALL cells are altered, with the hope that we can use this as a vulnerability for developing new therapies. We are particularly interested in drugs that alter how the cells produce a building block called methionine, and we are testing how these drugs work in T-ALL. Our ultimate goal is to find effective and non-toxic treatments for T-ALL.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Childhood brain tumors are a major cause of death for children. Medulloblastoma is one of the most common brain cancers in children and also one of the most difficult to treat. These children typically need extensive surgery, chemotherapy, and other treatments. Unfortunately, even with these treatments, many children with this cancer die from their disease. I am a pediatric neuro-oncologist, and it is my career hope to bring new therapies for medulloblastoma from the lab into the clinic.
My research studies why some children with medulloblastoma do not respond to treatment. I have made several discoveries that point toward new biology within the cancer cells that promote its growth. I have particularly focused on a new category of genes that we have recently described, called microproteins. These are small proteins that were missed in prior research on this cancer, and we have found that they are important for the ability for cancer cells to survive. I am optimistic that these discoveries are pointing towards new treatment options. To grow this vision, this V Foundation award will allow me to focus on studying certain new genes that we hope will lead to new treatments. Through this work, I hope to make new discoveries in medulloblastoma that are important for patients.
We are trying to find out why some ovarian cancer patients don’t respond to chemotherapy. Even though many patients start off well with the treatment, most eventually become resistant to it. When that happens, the only option left is to focus on making the patient comfortable, not curing the cancer.
To solve this problem, we need to understand what causes this resistance so we can develop new treatments. In our study, we found an important factor linked to this resistance by looking at patient data. Early tests suggest this factor might affect immune cells and cause resistance. We will investigate how this factor works and test new ideas using animals, patient samples, and state-of-the-art technologies.
Glioblastoma is a fast-growing and deadly brain cancer. Current treatments, like brain surgery, chemotherapy, and radiation, help, but most patients live for only about one year. Older patients with glioblastoma tend to do worse than younger patients, but we do not fully understand why. We believe that changes in the brain as people get older might help the cancer grow faster. Our project will explore whether changes in a part of the brain called white matter make it easier for glioblastoma to grow in older patients. Studying this in humans is difficult because it’s not safe to measure these changes in the brain while a patient is alive. To solve this, we will study mice, which have brains that change in similar ways as they age. We will examine whether tumors grow in the white matter more often in older mice compared to younger ones and try to identify the cells that allow this growth. To confirm our results, we will also study the white matter of human patients who died from glioblastoma to check if older patients are more likely to develop tumors in this area. The results from our study will help explain why glioblastoma is worse in older patients. This knowledge could help us find new treatments that slow tumor growth and help patients live longer.
Immunotherapy works by boosting the immune system to attack cancer cells and has improved the survival of many patients. An increasing number of cancer patients are now receiving immunotherapy, but there is no reliable way to predict who would have a good response. In addition, patients can experience a common side effect of immunotherapy, when the activated immune system attacks healthy organs, known as immune-related adverse events (irAEs). These side effects are often hard to diagnose until they have caused significant organ damage and can be life-threatening if not treated promptly. We have developed a new method, MethylSaferSeqS, that can provide an accurate measurement of the amount of remaining cancer in the body and detect early irAEs – all with a single blood test. MethylSaferSeqS can be applied to improve the care of cancer patients in several ways. First, it provides an early readout of treatment response and can identify the patients for whom immunotherapy is not working. These patients should be promptly switched to another therapy that could be more effective. Second, an accurate measurement of the remaining tumor in the body after completion of immunotherapy can identify the patients who should undergo additional treatments, such as surgery or chemotherapy, that would improve their chance of a cure. Lastly, an early detection of irAEs will allow timely treatments before serious damage is done to healthy organs. We will apply MethylSaferSeqS to samples collected from colorectal cancer patients who are receiving immunotherapy to test these goals.
Uveal (ocular) melanoma (UM) is a rare type of eye cancer. When the cancer spreads to other sites in the body, outcomes are often poor. Unlike skin melanoma, UM does not respond well to new types of therapy focused on the immune system. Better treatments are urgently needed. Our lab has recently shown that UM tumors frequently lose a sex chromosome (Y in tumors from men, X in tumors from women). Loss of the male Y chromosome (LOY) in men and loss of one X chromosome (LOX) in women occurs in about half of tumors, thereby affecting many patients. We found that LOY is linked to worse survival, and that LOY and LOX can give clues whether a patient’s tumor will spread to other sites in the body. I now propose to study the exact role of LOY in UM with a combined approach. Using genome analysis, gene knock-outs and drug screens in uveal melanoma models, our team hopes to find the weaknesses of UM tumors with LOY. These weaknesses could suggest new treatments for patients. LOY is not limited to UM but also occurs frequently in other tumor types. Therefore, the proposed work has far-reaching implications for finding better treatments for many people living with cancer.
The immune system is your body’s resident doctor. Immune cells constantly examine the organs and tissues in your body. Most of the time, immune cells eliminate damaged or infected cells before they can make you sick. However, this process goes wrong in cancer. We now know that tumors use multiple strategies to hide from immune cells so that they can grow and spread throughout the body.
A new kind of medicine, called immunotherapy, teaches the immune system to recognize and destroy cancer. Some patients treated with immunotherapy cleared their tumors and remained in remission for decades – the closest we’ve come to a cancer cure. However, most patients with colorectal cancer, the second deadliest cancer in the US, do not benefit from existing immunotherapies. It is thought that these patients’ cancers have developed different or additional strategies to hide from immune cells – but how?
One way that immune cells examine cancer cells is by detecting the sugars, or glycans, they display on their surfaces. It was recently discovered that colorectal tumors decorate their surfaces with sugars that trick the immune system into thinking the tumor cells are healthy cells. Thus, glycans are emerging as a main strategy used by colorectal cancers to evade the immune system. This project will develop medicines that target these glycans as a new kind of immunotherapy. Our hope is that medicines targeting sugars can help improve outcomes for all patients with colorectal cancer.
Immune cells are always patrolling our intestines, even when we are healthy. This includes B cells, which produce antibodies. Antibodies are floating molecular fire extinguishers which bind to and neutralize infections. In our intestines, huge amounts of antibodies are made every day. These bind to the ‘friendly’ bacteria that we live with to make sure they are well balanced, which keeps us healthy. In inflammatory bowel disease (IBD), the intestine becomes damaged by the immune system and antibodies change which bacteria they bind to. This turns the population of gut-bacteria from friendly to harmful, and can cause IBD to become colorectal cancer.
We do not know which B cells make cancer antibodies, or how antibodies make bacteria harmful. To understand this, we need to know how dangerous B cells become selected to produce the antibodies that turn IBD into cancer. This requires special tools to tell the helpful cells apart from the harmful ones. We built mice with multicolored B cells so we can follow the B cells that become hijacked during IBD and cancer. We may then understand where cancer-causing antibodies are made, and what they bind to. By doing this, we hope to compile a list of common antibodies that are always made before IBD becomes cancer, and look for them as warning signs in IBD patients. This could give doctors more time to treat high-risk patients before tumors form. In the future, we hope our findings help design new cancer drugs to delete harmful B cells.
Every year, over 40,000 people are diagnosed rectal cancer in the US. Many of these patients will receive radiation treatment. Sadly, radiation does not cure all rectal cancers. Many non-genetic, or “epigenetic,” factors control how cancer cells are built and how they respond to treatment. Often, these factors mimic biology seen in normal, non-cancer cells. Radiation causes normal intestine cells to change into stem cells that repair damage. We suspect these radiation-induced stem cells also occur in rectal cancer. We propose to test whether these radiation-induced stem cells cause rectal cancer to resist radiation. We will also map out the epigenetic factors that allow these stem cells to arise. To do this we will use new methods we have developed to show the fine details of epigenetic regulation. From our data, we will discern new mechanisms of rectal cancer radiation response. We hope these studies will yield novel treatments to combine with radiation for rectal cancer.
