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
The Schwartz Lab studies two genes, SAMD9 and SAMD9L that are known to cause a bone marrow failure syndrome in children called myelodysplastic syndrome (MDS). There are no reliable pediatric MDS model systems, thus we have created one from a special type of stem cell that contains mutated SAMD9 or SAMD9L. It is important to have these new cell lines, because cells that we can obtain from patients do not grow well or for a long time making studying them very hard. We will perform several tests in our new model system to determine why mutations in SAMD9 and SAMD9L cause blood stem cells to die. Together with our cell lines we have also developed a second set of tools that will allow us to turn on or to turn off SAMD9 or SAMD9L without using interferon—an inflammatory substance in the cell that turns on many other cell processes including SAMD9 and SAMD9L. We have completed initial experiments that suggest that SAMD9 and SAMD9L are important in how cells communicate during inflammation and other immune responses. Our proposed experiments will further determine how disease-causing mutations in SAMD9 and SAMD9L disrupt communication in these important cellular pathways. Understanding how SAMD9/9L mutations effect the blood stem cells will help us determine the right treatment approach for patients with pediatric MDS, because some patients with SAMD9 or SAMD9L mutations may not need treatment at all.
Funded by the Dick Vitale Pediatric Cancer Research Fund and the V Foundation Wine Celebration in honor of Bob McClenahan
Leukemia is a blood cancer that can be fully treated with anti-cancer drugs in most people. However, many people with leukemia do not respond to these drugs and are at risk of dying. It is not known why some leukemias respond to treatment while others do not. We believe that the type of normal blood cell that becomes leukemic impacts the behavior of individual leukemias. We believe that if a normal blood cell possessing the ability to form many other types of blood cells (in other words, it is a blood ‘stem cell’) turns into leukemia, this leukemia will be hard to treat. On the other hand, if the normal blood cell does not possess such properties – it is a more mature blood cell – this leads to treatable leukemia. In this proposal, we will apply our experience in engineering different types of blood cells (stem cells and more mature blood cells) to become leukemic. We will ask how the type of healthy blood cell impacts the behavior of the resulting leukemia. We will use genetics to understand how the properties of normal blood stem cells are transferred to leukemia cells to impact aggressiveness. We expect that successful completion of this study will improve our understanding as to why some forms of leukemia are treatable and why some are not treatable. We hope that these conclusions can lead to better understanding of individual patient leukemias and improved treatments.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Rudd Foundation in memory of Leslie Rudd
Immunotherapy is a type of cancer treatment that boosts the body’s immune system so that it can fight the cancer. Whilst this type of treatment has proven very successful for certain cancers in adult patients, this approach has been much less effective for the treatment of cancer in children. One reason for this is that the immune system of children is very different from adults and may not respond to treatments designed to target adult immune cells. Remarkably little is known about the cell types in children that suppress anti-cancer immune responses. The Brown Lab recently discovered a new type of immune cell —Thetis cells — that may be pivotal in reducing the efficacy of immunotherapy in the very young. We hypothesize that Thetis cells help to “train” T cells not to attack the body’s own normal cells, and in so doing creates an immune environment that also tolerates malignant tumors. In this project, the Brown Lab seeks to reveal, on the molecular level, how Thetis cells work and thus how to create immune therapies for children while not provoking auto-immune diseases that overactive T cells sometimes cause.
Funded by the Dick Vitale Pediatric Cancer Research Fund in memory of Colby Young
Children with changes in a pair of related genes (named DROSHA and DICER1) can get cancer in their lungs, muscles, kidneys, brains, and other organs. This is because DICER1 and DROSHA normally turn off pro-growth signals. When these pro-growth signals cannot be turned off, cancer can arise. We do not know which pro-growth signals are most important. Our lab found that one of these pro-growth signals, named Igf2, may be one of the most important. We came across this idea through studying mice that develop brain cancer due to Drosha changes. This project will study how important Igf2 is. It will also examine exactly how Igf2 gets turned on. Lastly, it will test whether a drug that targets Igf2 will be effective in these cancers.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Medulloblastoma is the most common brain tumor in children. While doctors can cure most of these children, the treatments are very toxic and negatively impact these patients and their families for the rest of their lives. Thus, scientists are trying to finding new therapies that are more effective and less toxic. A handful of new drugs have been tested in the last few years in patients with medulloblastoma. Most of these new drugs initially show great efficacy. Unfortunately, tumors rapidly become resistant and return more aggressively. Sadly, when these tumors come back there is no good treatment available and most of these children die. Therefore, it is very important to find drugs that can stop the growth of the tumors and prevent their reappearance. A series of experiments allowed us to find an ideal candidate therapeutic for children with medulloblastoma tumors. These compounds that target a family of proteins named BET, will reduce the size of the tumors and prevent them from growing back in the future. We believe that our research will provide a game-changing therapy for patients with medulloblastoma and restore hope in these children with cancer and their families.
Pancreatic cancer is a deadly cancer. There are urgent needs to identify specific biomarkers in blood (proteins and metabolites) that are related to pancreatic cancer. The increased understanding of risk factors for pancreatic cancer can be useful to develop new strategy for predicting individual risk of developing this cancer. The proposed study using novel design and methods will help identify protein and metabolite biomarkers in blood causally associated with pancreatic cancer risk. Knowledge generated by this project will help us to better understand the etiology of pancreatic cancer and lay a solid foundation for future efforts of risk prediction of this deadly cancer. The identification of high-risk individuals can be useful for more specific, expensive, and/or invasive tests to identify disease at an early stage or for targeted prevention to reduce disease risk.
Colorectal cancer is the second leading cause of cancer related deaths worldwide. Alarmingly, recent studies show that its incidence is increasing in younger adults. Certain environmental factors, such as diet, can have an impact on colorectal cancer. Calorie dense, western diets can lead to energy imbalance and excessive weight gain, which is associated with higher risk of colorectal cancer. Since diet is a modifiable risk factor, it is important to understand precisely how diet composition and particular nutrients within the diet can affect colon tumor cells directly and indirectly. We plan to systematically examine how colon cancer cells become dependent on certain nutrients that are necessary for rapid tumor growth and progression. We will also test how relevant dietary nutrients, such as sugars and fats, change the function of support cells found within the tumor and influence tumor growth. Our hope is to identify vulnerabilities in colon cancer cells that we can enhance through nutrition and develop new treatments that will improve survival and quality of life for cancer patients.
The goal of this project is to make new drugs against ovarian cancer genes using a new drug discovery method. Ovarian cancer (OC) remains a deadly disease. OC will be diagnosed in over 21,000 women in the United States this year and 13,770 patients are expected to pass away during this time. While initial responses to the best anti-cancer drugs are frequent, most patients with OC will experience disease again after 24 months of treatment, and most women will unfortunately pass away from this disease within five years. Thus, there is an urgent need to make new drugs to treat ovarian cancer. The classic approach to drug discovery is both time intense and costly, and most cancer drug discovery is focused on making drugs against cancer proteins whose shape is considered readily ‘druggable’. Our central premise is that many ovarian cancer proteins can be drugged. To test our idea, we will use a new tool that finds druggable proteins by detecting drug binding to cancer causing proteins in OC cell lines and patient tumors. If successful, this program should develop a new class of anti-cancer drugs to help women suffering from OC.
Fighting cancer is like a game a chess: each treatment can be followed by the adaptation of the tumor. Our next move requires the development of a novel treatment strategy. This is however a difficult task.
My research goal is to develop novel strategies to treat breast and ovarian cancers that are resistant to common drugs. Many breast and ovarian cancers are no longer capable to correctly repair DNA when it is broken. This Achille’s heel can be used to eliminate cancer cells without damaging healthy tissues. My research team has identified a novel protein that help repair DNA and that is essential in these cancers. Our goal is to develop a drug against this protein and to test if we can use it to kill certain cancers that became resistant to current treatments.
Funded by the Constellation Gold Network Distributors
Genetic information is carried in DNA, which is present in every cell of our bodies. Most cells have 46 chromosomes, which carry DNA within the cell. However, more than 90% of tumors have cells without the correct number of chromosomes. These cells are called “aneuploid”. Some whole chromosomes or large chromosome fragments may be duplicated or lost. Aneuploidy is a contributing factor in cancer formation. However, its exact role in this process is an unanswered question in cancer biology. The goal of this research is to understand the effects of different changes in chromosome number.
For our studies, we make use of a new technology that allows us to cut chromosomes at specific locations. With these experiments, we can study the effects of changes in large chromosome segments. Our current focus is a type of cancer called squamous cell carcinoma (SCC). In this cancer type, large pieces of chromosome 3 are affected. Here, we will uncover the interaction between chromosome 3 changes and DNA mutations. We will also create a human cell model of SCC. These studies address a gap in our understanding of aneuploidy in cancer by studying the effects of specific sets of chromosomal changes. With knowledge of how these chromosomal changes contribute to cancer formation, we will uncover new ways that cells can become cancerous. A better understanding of paths to disease formation will be crucial for designing new cancer treatments.
