Grants Search Results

Neuroblastoma is a pediatric cancer that originates from mistakes in nerve cell development. Limitations in our mechanistic understanding of disease onset and progression have led to inaccurate patient risk predictions and over-treatment of infants, with long-term side effects. Recently, Dr. Kulesa and colleagues developed a computational model to predict neuroblastoma disease outcome based on a network of six development genes of receptor tyrosine kinase signaling that is more accurate at early disease stages than any current gene list algorithm. What remains to be determined is whether this model can be refined to increase its predictive value and tested to simulate hypothetical treatment strategies with individual patient data. To address these questions, he will include MYCN into the network model, a proto-oncogene gene that is correlated with poor prognosis, and compare model and experiment results of network perturbations that simulate targeted treatments. Dr. Kulesa will take advantage of acquired human neuroblastoma cell lines and our ability to modulate these genes in culture, and patient data from large-scale neuroblastoma genomic databases and published studies. At the conclusion of our study, he will have a better understanding of the mechanistic basis of neuroblastoma disease progression and a refined computational model to more rapidly and accurately predict individual patient disease outcome.

Young children with Down Syndrome are at very high risk of developing cancer of the blood (leukemia) before the age of 4. These leukemias arise from abnormal blood cells that are first detected in newborns with Down Syndrome. Studies suggest that the abnormal blood cells arise in the early embryo before a permanent blood system is set up. Dr. Palis has developed a unique way to study the biology of these abnormal blood cells. Researchers can now study the path from abnormal blood cell to leukemia in a dish. Using this system, he will learn how certain genes drive the change from 'abnormal blood cell' to 'cancer blood cell' that occurs specifically in very young children with Down Syndrome. Long-term goals are to prevent leukemia from forming and to develop safer treatments for those children with Down Syndrome who develop leukemia.

Dr. Rowe is applying stem cell biology to understanding childhood leukemia. Overall, pediatric oncologists have made remarkable progress in treating children with leukemia with chemotherapy, but some children have forms of leukemia that don't respond well. Dr. Rowe is interested in better understanding what makes this subset of leukemias resistant to treatment. To do this, he is developing new models of these unfavorable forms of leukemia so that he can understand precisely how normal blood cells become leukemic blood cells. If Dr. Rowe can achieve this, then researchers can find new ways to more effectively treat these forms of leukemia.

Over the past 10 years, we have made great strides in the diagnosis of Medulloblastoma, the most common malignant brain tumor of childhood. These advances have come from widely collaborative efforts to perform DNA sequencing on tumor specimens. This effort led to the identification of major subtypes of Medulloblastoma and a recognition that these subtypes are associated with differences in response to standard treatments and survival. Lagging behind, has been an understanding of the molecular mechanisms that drive relapse of Medulloblastoma. This occurs in 30-40% of Medulloblastoma patients and as yet, there are no curative options. As the recipient of the Thumbs Up Fund to Honor Brett Haubrich St. Baldrick's Research Grant, Dr. Rubin and his team members are proposing a novel clinical trial to address this pressing unmet need. Their trial, brings together what has been learned from sequencing Medulloblastoma and the recently developed ability to test the sensitivity of an individual patient's Medulloblastoma cells to hundreds of drugs simultaneously. The long-term goal is to use the combination of drug testing and DNA sequencing to design personalized treatments for relapsed Medulloblastoma patients. Success in this effort would not only provide new treatments for relapsed Medulloblastoma, but would also provide a new paradigm for personalized approaches to the treatment of all pediatric brain tumors.

A portion of this grant is funded by and named in honor of The Thumbs Up Fund to Honor Brett Haubrich, a St. Baldrick's Hero Fund. Brett is remembered for his kindness, his joy in making others happy and his faith even through his 3 ½ year battle with anaplastic astrocytoma, a difficult to cure brain cancer. Brett was diagnosed at the age of 11 and endured treatments and laser surgery which impacted his motor and speech functions. Yet he was always positive, often giving his signature “thumbs up” as a symbol of hope. In his honor, Team Brett began participating in St. Baldrick’s head shaving events in 2015 and each year, raised over $10,000. This Hero Fund hopes to raise funds for childhood cancer research for brain tumors like Brett’s so other families would have more options for cures.

The proto-oncogene MYCN is amplified in approximately half of patients with high-risk neuroblastoma. At relapse, tumors from high-risk patients typically activate a pathway called "MAP kinase signaling" through genetic mutations including loss of NF1, which normally dampens MAP kinase function. Since relapsed neuroblastoma is generally therapy resistant, these data suggest that MAP-kinase activation contributes to therapy resistance. Does MAP kinase signaling contribute to therapy resistance in MYCN-amplified neuroblastoma at diagnosis? Dr. Weiss proposes that dependence on increased MAP kinase signaling in MYCN-amplified neuroblastoma enables rare cells within this heterogeneous tumor to evade chemotherapy. This therapy-resistant population then undergoes selection for further activation of MAP-kinase signaling, reinforcing therapy resistance. How does MYCN drive MAP kinase? The NF1 tumor suppressor blocks MAP kinase signaling. Mis-splicing of the NF1 messenger RNA in neuroblastoma cells results in NF1-23a, a protein with decreased ability to block RAS. Inclusion of NF1 exon 23a is regulated by the RNA splicing proteins "T-cell intracellular antigen 1" (TIA1) and "TIA1 Like gene" TIAL1, both of which are MYCN target genes. If activation of TIAL and TIAL1 (TIA/L1) in MYCN-amplified neuroblastoma activates MAP-kinase signaling in primary tumors at diagnosis, does traditional treatment of these tumors select for further flux through MAP-kinase signaling, to enhance resistance at relapse? This is the issue that Dr. Weiss' proposal addresses. Successful completion clarifies the importance of MYCN-TIA/L1 axis as a driver of resistance in neuroblastoma, and suggests a a translational path to improve outcomes in neuroblastoma.

Dr. Weiss' grant is generously supported by the Arden Quinn Bucher Memorial Fund, a St. Baldrick's Hero Fund. Arden’s intelligence, empathy, and dynamic personality charmed everyone and is now her legacy. Before her neuroblastoma diagnosis on October 11, 2007 at age two, she happily played with boundless energy and imagination. Even throughout her difficult months of treatment, Arden bravely managed to keep smiling and learning. This fund supports St. Baldrick’s mission: funding the most promising research, wherever it takes place to provide kids fighting cancers less toxic, more effective treatments allowing them to live longer, healthier lives.

Therapies that only inhibit tumor cells but not normal cells are missing for the deadly childhood brain tumor medulloblastoma. As the recipient of the Miracles for Michael Fund St. Baldrick's Research Grant, Dr. Zhang has identified a promising drug target in medulloblastoma. This project aims to study the role of the target in medulloblastoma and evaluate the therapeutic potential of inhibiting this target using cutting-edge technologies and models.

This grant is funded by and named for the Miracles for Michael Fund, a St. Baldrick's Hero Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was 6 years old. After completing initial treatment, his cancer relapsed within a year and he passed away at the age of nine. Michael had unwavering faith and perseverance, wanting most of all to make others happy. This fund honors his tremendous strength to never ever give up.

The human immune system is astonishing in its ability to eliminate cells and organisms that give rise to disease. This process of immune surveillance is one of the last lines of defense that protect both adults and children from cancer; however, researchers have found that dysfunctional immune responses can permit cancerous leukemia cells to grow uncontrollably in the body. In this work, Dr. Dreaden will improve upon a drug that attempts to restore immune elimination to leukemia by redirecting a subset of immune cells, so-called T cells, to bind with and kill cancerous cells. By tethering such drugs with molecules that stimulate T cells to multiply, and possibly enable these cells to recognize leukemia cells again at a much later date, he aims to further improve both the strength and durability of responses to this promising class of immuno-therapy. Already, Dr. Dreaden and colleagues have made and screened more than 45 of these unique, multi-functional therapies and aim here to study the precise mechanics by these drugs act on immune cells, as well as their ability to impart memory-like immune responses to leukemia. Given the modular nature of this treatment approach, it could be rapidly extended to a range of other cancer cells, immune cells, and immune stimulating factors in the future.

This grant funds a student to complete work in pediatric oncology research for the summer. There has been little success in curing high risk AML patients, with survival rates remaining at < 25%. This highlights our current reliance on highly intensive cytotoxic therapies and stem cell transplant, and their inadequacies. This project studies the combination of novel target discovery with state-of-the-art stem cell expansion technology. Protein science provides a unique opportunity to generate one of the most impactful therapeutic discoveries in childhood AML in the last 40 years, with minimal toxicity. The summer intern will assist in investigating the impact of drugs on cancer targets while minimizing toxicity toward healthy cells. Results will be used to help identify critical genes involved in cancer growth and disease resistance, and to leverage future work in drug development.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Children diagnosed with leukemia are often effectively treated in the beginning, but later relapse with their disease. Scientists now feel that this is in part due to the sanctuary that the bone marrow (BM) provides the leukemia cells. This prevents complete elimination and can set children up for relapse. This study aims to understand how the BM protects leukemia cells. Once we have identified the mechanisms by which that happens we can then begin to develop drugs to prevent it. This lab has recently identified an inflammatory process by which leukemia cells change the BM function and think this is a root cause of disease persistence and relapse. The project will test this hypothesis and find out how to prevent the leukemia from changing the BM and causing relapse.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. This project will validate a drug for the medulloblastoma, a type of brain tumor, specifically tumors that spread from the original cerebellar location to the covering of the brain and spine (the meninges). This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds an undergraduate student and a medical student to complete work in pediatric oncology research for the summer. Neuroblastoma is a pediatric tumor in which a large subset has very poor survival. Researchers are trying to understand what makes this subset so deadly and have developed a system to test combinations of genes apart and together to determine how they could make certain neuroblastoma more aggressive. They will test whether certain mutations may make the neuroblastoma tumor cells more invasive and if these mutations could cause other critical gene expression changes in high risk neuroblastoma.

This grant funds two undergraduate students to complete work in pediatric oncology research for the summer. Tumors have extensive mutations in their DNA which play important roles in cancer development. Particular mutations that are frequently found in tumors are likely important for promoting cancer development. BubR1 is a protein that regulates the proper separation of DNA during cell division, and therefore plays an important role in suppressing cancer formation. A mutation in BubR1 (R249Q) is specifically observed in approximately 15% of pediatric cancers and is not found in adult cancers. Researchers will study this mutation and results may identify a unique mechanism of tumor development controlled by BubR1 specifically during developmental processes, uniquely promoting pediatric cancer. This project will provide an opportunity for these two students to spend the summer performing biomedical science research utilizing well-established and easy to learn techniques, to enhance their excitement in pediatric cancer research.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Ewing sarcoma is a cancer that primarily occurs in children, adolescents, and young adults. While we don't know why certain people get Ewing sarcoma, we do know that most patients have the same problem with genes in their cancer cell. Just as genes affect your eye color, the Ewing sarcoma cells have a special gene, EWS-FLI1, that keeps the cancer growing. EWS-FLI1 is critical for Ewing sarcoma cells to survive. If you turn off EWS-FLI1, Ewing sarcoma cells die. This project will study exactly how YK-4-279, a chemical in a new drug in clinical trials, affects key survival processes, called transcription and splicing, to enable design of optimized drugs. This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. DIPG's are the worst type of brain cancer children can get; there is no cure. This project will try a new approach to change that. Using large publicly available datasets from large experiments, 4 drugs have been identified that theoretically can slow down the growth of DIPG tumors. Researchers will test these four drugs against several DIPG models generated from patients. If results are positive, this could lead to new treatments for this deadly disease.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. High risk neuroblastoma remains a challenge to cure with only 50% survival, despite multi-modality treatment. Natural killer (NK) cells have been previously shown to have activity versus neuroblastoma but have not been consistently successful in clinical trials. In similar fashion to how people receive flu shots, this project will treat bone marrow transplant recipients with 3 doses of a vaccine, with or without anti-PD1 therapy to stimulate T and NK cells, to introduce their immune system to what neuroblastoma looks like, so in the event this tumor tries to grow, the immune system will stop it and kill it before making the patient sick. This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds two students to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Project 1: Neuroblastomas are an enigmatic cancer of childhood with subtypes that have extremely good or poor survival. Poor prognosis neuroblastomas contain normal immune cells that help tumors grow. Important questions are 1) what is the repertoire of immune cells in neuroblastomas at time of diagnosis, 2) how the interplay between normal and tumor cells changes when tumors recur. The Summer Fellow will analyze images of tumors at recurrence and compare to the diagnosis images. These findings will provide insights into the types of immune cells that cancer cells rely on and may allow identification of new targets of therapy. Project 2: Decline in brain function may happen after irradiation to the brain in children. It is hard to predict the extent and speed by which it happens. There is suggestion that more rapid injury happens in areas with iron deposition. Using a novel MRI method that allows chemical identification and quantification of iron in the brain, the Summer Fellow will characterize the imaging changes in white matter of the brain in children who have been treated with radiation for their brain tumors. This will allow to then correlate the changes with future outcome of their cognitive function.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Diffuse intrinsic pontine glioma (DIPG) is a type of children's brain tumor that currently has no cure or effective therapeutic options. This proposal aims to understand whether the target drug of ONC201, ClpP, can be targeted using novel compounds representing new potential therapeutics in DIPG.

Acute lymphoblastic leukemia (ALL) remains the most common cancer of children and young adults. Despite intensified treatments that achieved cure rates around 85%, there is a number of children who will relapse and succumb to therapy-resistant disease. One of the revolutions in the treatment of human cancer the last decade was immunotherapy, the ability of our own immune system to fight cancer. Unfortunately, despite its successes in a number of solid tumours, immunotherapy has not really impacted the treatment of leukemia, with the exception of CAR-T cell treatment of pediatric B-ALL. Indeed, some frequent types of pediatric ALL, and specifically T cell ALL (T-ALL) and its subtypes, have no immunotherapy treatment options. We believe that this is because we still don't understand how the cells of the immune system interact with the leukemia. Actually, researchers don't even know what type of immune cells are there available to fight the disease. Dr. Aifantis is applying a number of single cell techniques to create a map of the immune cells in the bone marrow of children with T-ALL. He is doing this at diagnosis of the disease, after treatment (remission) and when the children relapse. These studies will offer the first map of the immune system in pediatric ALL and will enable researchers to propose ways to activate the immune system to fight the tumour.

In the new era of personalized medicine, Ewing sarcoma still relies on decades-old chemotherapy options, where aggressive treatments are met with poor disease outcomes. Ewing sarcoma is a devastating disease that affects children and young adults age 5-16. Based on treatment outcome and patient qualities of life, Ewing sarcoma is in desperate need of research and development of new therapeutic options. One of the key observations of Ewing sarcoma made back in the 1930s is the accumulation of a large amount of glycogen. Glycogen is a sugar molecule that our body uses to store energy; only specific organs such as the liver and muscle are capable of producing glycogen. The ability of Ewing sarcoma tumors to store large amount of glycogen has been forgotten until now. Dr. Sun aims to understand the reason behind large glycogen accumulation in Ewing sarcoma and exploit the glycogen deposits as a possible drug target for the treatment of Ewing sarcoma. The successful completion of this project will bring new hope to this century-old disease and facilitate the development of the next generation of novel therapeutics specifically for Ewing sarcoma.

A portion of this grant is funded by and named for Julia's Legacy of Hope, a St. Baldrick's Hero Fund that honors her positive and courageous spirit and carries out Julia's last wish: "no child should have to go through what I have experienced". Diagnosed at age 16 with Ewing sarcoma, Julia fought cancer and survived only to be stricken in college with acute myeloid leukemia, a secondary cancer as a result of treatment. Through this Hero Fund, her family hopes to raise awareness and funds for childhood cancer research especially for Adolescent and Young Adult (AYA) patients.

Eight out of ten children with cancer will be cured and will become long-term survivors. However, children with cancer experience serious side-effects during, and even after, finishing treatment that negatively affect their well-being. There is also variation and unpredictability in who will experience these side-effects. Additionally, despite the best treatments, some children are not cured and ultimately lose their fight against cancer. Dr. Wadhwa is examining the role played by body composition (fat and muscle) of children with cancer on side-effects and cure rates. The dose of chemotherapy has been based on height and weight. Dr. Wadhwa and colleagues believe that body composition plays an important role in how the chemotherapy is distributed in the various compartments of the body. They are using routinely performed CT scans to determine body composition and plan to identify a method to personalize the chemotherapy dose for each child and minimize serious side-effects but at the same time, maximize cure rates.