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 Constellation Gold Network Distributors
Cancer is a disease of uncontrolled cell growth. As the disease advances, the cancer can leave the original site and spread to other parts of the body. The ability to grow and invade is energetically costly though. Thus, cancer cells will modify their metabolism to meet these high energy requirements. This includes aggressively using nutrients to produce more energy (ATP), making building blocks for growth (protein, plasma membranes, DNA) and finding ways to overcome metabolic stress (e.g., reactive oxygen species). In other words, if we can identify metabolic changes that occur only in cancer, then impacting the altered metabolic pathways could enable us to selectively kill cancer cells and not impact normal cells.
We are interested in the metabolism of the sugar molecules fructose and mannose. Cells generate mannose-related metabolites from fructose. We discovered that the balance between fructose and mannose is important when lung cancer becomes aggressive. Only these aggressive lung cancer cells were killed when the conversion of fructose to mannose was disrupted. This project will examine how fructose-mannose metabolism is changed when lung cancer becomes aggressive. We will also determine why this metabolic pathway is critical to keep these cancer cells alive. To accomplish the task, we will remove a critical enzyme in fructose -mannose metabolism, and then utilize a series of experiments to characterize the metabolism of these cancer cells. If successful, this study will provide clues as to why drinking soda (fructose) can increase cancer risk while consuming mannose slows tumor growth. Ultimately, we want to answer whether targeting this sugar pathway can help treat patients.
Funded by the Stuart Scott Memorial Cancer Research Fund
Cancer cachexia is a wasting disease with significant fat and muscle loss occurring in 1/3 of all patients with cancer and causing 1/3 of all cancer patient deaths. It is also makes patients not want to eat. Cancer patients with cachexia live half as long as patients with the same cancers without cachexia. These patients have a poor quality of life which prevents them from taking medications to treat their cancer as well. Currently there are no treatments for this wasting disease. Therefore, clinicians often use medications that are not approved by the government to treat cancer cachexia with little benefit.
We aimed to better understand how cancers can cause cachexia wasting in order to create new medications for this disease. Our research has identified a molecule made by cancers that causes fat breakdown and causes decreased food intake. These cancer-secreted factors do this by acting directly on the fat and the part of the brain that controls food intake. These factors also reprogram the fat to secrete other factors that also affect the brain’s appetite center. We believe the combination of these events is responsible for the wasting seen in these cancer patients. Our research proposal will try to identify how these molecules affect the fat tissue and the brain to cause cancer cachexia to help us develop new medications for this under-treated disease. Creating a treatment for cancer cachexia will improve cancer patients’ quality of life and overall life span.
Cancer treatments have improved over the past 30 years, but many patients still die from the disease. A new type of drug has been found that causes the patient’s body to attack the cancer. This new drug, called “immunotherapy”, works very well for some people but not for many others. Our studies try to find ways to make this treatment work for more patients. We are especially interested in how radiation can be used to improve immunotherapy and have found a new way that these two treatments work together. Our current work is focused on finding other ways that these treatments work together. We are especially interested in learning how we might improve how patients feel during and after treatment by reducing the side-effects of therapy. Overall, the major goal of our work is to increase the success of cancer treatment for all patients and to improve their overall quality of life.
Volunteer Grant funded by the V Foundation Wine Celebration in honor of Roger and Sally Krodel’s granddaughter, Angie Cerreta-Palauqui
Therapies to kill cancers typically get rid of the dividing cells. However, the few that remain are a mixture of resistant cells that can return later to form more tumors. This is a difficult problem to solve. My research looks into finding out which genes cancer cells choose to use when they are not dividing to repair their damaged DNA and survive. Our goal is to develop treatments that will interrupt those genes that cancer cells use so they can die. We also want to develop treatments that can not only work to stop many different types of cancers, but that can also work in combination with other therapies to block the return of cancers later in life. The potential long-term success of our research will help to ease the anxiety of cancer survivors by extending the cancer-free period indefinitely.
Funded by the Constellation Gold Network Distributors
My research is focused on understanding the role of genetic abnormalities in prostate cancer treatment resistance. Prostate cancer is one of the most common cancers in men, but what makes prostate cancer deadly in some men, but not others? The answer lies in the DNA of prostate tumor cells. Abnormal changes can occur in the DNA of tumor cells and give them the ability to resist standard treatments. Monitoring tumor DNA over time could uncover these changes. As the cancer progresses, tumor cells can move and grow in distant organs. Often, obtaining tumor cells from these organs is painful and difficult. What if tumor cells and its DNA were easier to access? We address this problem by using an exciting method, called a “liquid biopsy”, to measure tiny amounts of DNA that are released from tumor cells into the blood. We develop new computational techniques, combined with genetic sequencing, to reveal “signatures” of tumor DNA alterations from the blood. These signatures could allow oncologists to track whether a patient is responding well to treatment. They could also help predict whether a patient’s tumor has the potential to resist treatment. Ultimately our work will provide new tools to help doctors care for patients with less discomfort, more accuracy, and greater precision.
Funded by the Stuart Scott Memorial Cancer Research Fund
Ovarian cancer is one of the deadliest cancers among women worldwide. In 2019, nearly 22,240 new cases of ovarian cancer will be diagnosed in the US, and approximately 14,070 women will succumb to this disease. Most women respond well to the standard treatment, however, the majority of these patients (with estimates up to 75%) experience a recurrence of the disease due to acquired resistance of the tumor cells to chemotherapy.
This proposal is aimed at understanding what makes ovarian cancer cells resistant to therapy with the goal of discovering new avenues for therapeutic intervention. We will use state-of-the-art genome sequencing techniques to measure the changes that occur in primary ovarian tumor samples compared to recurrent tumor samples collected from the UNC Cancer Hospital. Our goal is to define how genes are being regulated in ovarian tumors in order to identify the molecular switches that are responsible for turning on genes that give rise to resistance. We hypothesize that these molecular switches (known as enhancers) are hijacked by the tumor cells for the activation of genes that give rise to resistance. We aim to identify their locations throughout the genome and determine which ones are responsible for drug resistance. Completion of this project will increase our knowledge about an understudied new facet of ovarian cancer, advance the way cancer research is conducted, provide a new set of biomarkers with diagnostic and prognostic potential, and highlight new targets for controlling cancer cell growth.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Rhabdomyosarcoma is the most common childhood cancer. Its most hard-to-treat subtype, fusion-positive alveolar Rhabdomyosarcoma (FP-ARMS), is mainly caused by chromosome translocations that form a “fused oncogene” called PAX3-FOXO1 or PAX7-FOXO1. Although the genetic mutations leading to FP-ARMS has been known for decades, the effective therapy to treat FP-ARMS patients is still lacking: less than 50% of the patients are cured, and patients survival rate is less than 10%. In FP-ARMS translocation, a piece of DNA is “fused” to another piece of DNA. Such fused DNA sequence not only consists of the protein-coding genes but also of the non-coding DNA sequences. These non-coding sequences used to be called as “junk DNA”, but more and more studies have shown that they play essential roles in human diseases, including cancer. However, in FP-ARMS, we know very little about whether or how the “fused” non-coding DNA sequences contribute to cancer. In this study, we will take advantage the newly developed technology to address this question that has never been asked: how the “fused” non-coding DNA sequences contribute to tumor development. Our work will help to understand the mechanism that control FP-ARMS development, and in the future, to provide new drug targets for better therapies. More importantly, since chromosome translocation is frequently observed in many childhood cancer types, our pioneer work will also establish the new methods that can be applied to study other pediatric cancers.
Funded by the Stuart Scott Memorial Cancer Research Fund
Normally, the cells of our body grow and divide only when needed. In cancer, however, this organization breaks down and cells grow out of control. Our lab studies signaling pathways that act as the cell’s circuitry and control when it grows and divides. We also study cellular metabolism, which consists of the chemical reactions a cell uses to turn nutrients into energy and cellular building blocks. Growth signaling pathways are often what become mutated and abnormally activated in cancer, in part, because they play important roles in controlling metabolism. We are particularly interested in a critical metabolic cofactor known as Coenzyme A, which is required to produce cellular energy and building blocks. We have gathered evidence that some cancer cells may have a greater need for Coenzyme A compared to normal cells. Therefore, it may be possible to kill certain tumors before damaging normal tissues by targeting Coenzyme A metabolism. We will characterize specific mutations that may make cells vulnerable to this treatment, and test this treatment concept in cancer cell cultures and mouse tumors. Our basic research into whether this treatment has promise is the necessary first step towards developing a potential new drug that may one day be used to successfully treat patients.
According to estimates from the International Agency for Research on Cancer, worldwide, there were 18.1 million new cancer cases diagnosed with 9.6 million deaths in 2018. In other words, one in 5 men and one in 6 women experience cancer during their lifetime, and one in 8 men and one in 11 women die from the disease. As such, there is an urgent need for finding better treatments to reduce cancer-associated death. BRCA1 and BRCA2 are two genes that, when mutated, can cause cancer. Studies by many research groups have revealed critical roles of BRCA1 and BRCA2 in protecting our genetic material from damage caused by sunlight, radiation, and other environmental exposures. While BRCA mutations have been linked to a greatly increased risk of developing cancer, we do not yet fully understand the biological process of DNA repair mediated by the BRCA genes. This poses a challenge for patient counseling, determining prevention strategies, and the formulation of treatment plans when disease strikes. Here, we describe a research project to study BRCA1 and BRCA2 designed to fill this knowledge gap. The information and tools from our work will help explain why BRCA mutations cause disease and help formulate treatment regimens that are more effective than current ones.
Head and neck tumors are composed of cells that are not all the same, but instead have different functions, much like bees in a hive. While some cells act like drone bees that are primarily responsible for expanding and growing the colony (or in this case, tumor), others are responsible for directing and orchestrating the tumor like a queen bee. Still other cells mimic worker bees who travel outside the hive and are responsible for the spreading the tumor to new locations. We are interested in these worker bees of head and neck cancers and understanding what triggers them to exit the hive. In particular, we are trying to identify the specific genes that serve as markers of the worker bees, in order to determine if they are present in tumors and whether they can help to predict when a cancer may spread. We are also trying to understand the specific genes that allow these worker bees to perform their function. Much like a specific wing shape or other adaptations worker bees have in nature, we are curious about whether these cells have specific cellular machinery they use to spread beyond the tumor. Together, these studies could help us develop new ways of identifying patients at risk for their cancer spreading as well as new treatments to prevent the spread of cancer all together.
