Grants Search Results

Acute lymphoblastic leukemia (ALL) is the most common cancer of children, and although treatment is considered largely successful, in many cases leukemic cells stop responding to chemotherapy and re-emerge. As a consequence, ALL relapse remains a leading cause of childhood cancer-related death. Dr. Aifantis will test the possibility that the bone marrow microenvironment surrounding the leukemia supports the growth of disease and protects leukemia cells from chemotherapy. Together with colleagues he generated the first map of the ALL immune cell microenvironment allowing identification of novel players within the remodeled leukemic bone marrow that promote leukemia survival. They found that high levels of a specific cell type, known as non-classical monocytes, in ALL patient blood and bone marrow correlates with inferior patient survival. They demonstrated that depletion of leukemia-supporting monocytes enhances killing of leukemic cells with specific ALL therapies. In this project Dr. Aifantis will investigate the processes giving rise to monocytes capable of supporting leukemia survival. Further, he will use novel model systems to test whether targeting monocytes enhances responses to a range of existing ALL therapies as well as emerging approaches, such as Chimeric Antigen Receptor (CAR) T-cell therapy, that utilize a patient's own immune system to kill leukemic cells.

Pediatric cancers are often comprised of mixtures of cells with different characteristics. Some of the most important differences relate to chromosomal changes, with some cells having a normal or nearly normal chromosome profile, others having altered numbers of intact chromosomes, and yet others having extra or missing copies of one or more chromosome segments. Prior studies have shown that cancers with more segmental changes are usually more aggressive and therapy-resistant, but the specific effects associated with the different chromosomal changes are unknown. Here Dr. Cobrinik and colleagues will define the effects of such changes in two pediatric cancers -- retinoblastoma and neuroblastoma -- by isolating individual cells within the tumors that either have or lack specific chromosome changes, comparing their overall gene expression and cell signaling profiles, and identifying the critical changes that increase malignancy. The study involves three investigators with expertise in neuroblastoma, retinoblastoma, and a novel single cell sequencing approach that enables us to distinguish and characterize the chromosomally distinct cells within individual tumors in unmatched detail. This study is expected to reveal the most central features that distinguish more versus less aggressive cancers, as a critical step towards targeting and subduing the more aggressive and lethal cells within individual tumors.

Precise understanding of the basic mechanisms by which childhood cancers develop is essential to design tailored and superior treatments for cancer patients. These treatments are expected to cure and avoid long-term complications in cancer survivors. In many instances, we turn to models to reproduce human cancers, but the success of this strategy depends on how accurately we can unravel the origin of the disease. This project is based on Dr. Dominguez-Sola and colleagues recent findings on the origins and cellular basis of Burkitt lymphoma, a most aggressive form of childhood lymphoma with little treatment alternatives. This project will use unprecedented models of this cancer type to expand our understanding of the mechanisms of disease and identify therapeutic strategies that are less toxic, more effective, and superior to those currently available in the clinic.

As the recipient of the Jack's Pack - We Still Have His Back St. Baldrick's Research Grant, Dr. Eischen is focused on researching Burkitt lymphoma, a blood cancer that predominately develops in children and young adults. The goal of this proposal is to investigate a novel approach to eliminate Burkitt lymphoma cells, and particularly difficult to treat relapsed and refractory to treatment Burkitt lymphoma. Although five-year survival rates for Burkitt lymphoma is 85-90%, treatment is toxic with associated complications, and children that relapse or that are resistant to treatment have poor survival rates even with additional therapy. Therefore, more research and new treatments are needed for Burkitt lymphoma. This project stems from a paradigm-shifting discovery she recently made and will use an innovative approach that includes testing newly designed compounds to target a specific protein called Mdm2 in Burkitt lymphoma cells causing their death. This approach should also cause the death of Burkitt lymphoma cells that contain mutations in a gene that make them resistant to many current therapies and that reduces patient survival. Completion of the research will result in increased understanding of the role of Mdm2 in human Burkitt lymphoma cell survival, testing of new compounds that target Mdm2, and pre-clinical tests with the compounds on human Burkitt lymphoma cells. The long-term goal of these studies is to have an improved, more effective treatment approach for non-Hodgkin's lymphomas, and particularly those lymphomas that are resistant to current therapies. This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Alveolar rhabdomyosarcoma is one of the most aggressive and difficult to treat tumors in children. If not caught early, metastatic disease has a dismal 5-year survival of less than 5%, even after the most intensive chemotherapy possible. Even in the rare circumstances when these children do well, the long-term side effects of the intensive chemotherapy are debilitating. We can, and must, do better. We have known for some time that the cause of alveolar rhabdomyosarcoma in 60% of the most aggressive cases is a specific genetic abnormality. This genetic mistake creates a new gene, and Dr. Hiebert will determine how this new gene causes cancer and determine what would happen to these sarcoma cells if we had a drug specific for this new gene. To do this, he has engineered alveolar sarcoma cells grown in the lab so that this cancer gene can be quickly turned off by an existing drug. This allows, for the first time, the treatment of these sarcoma cells with a specific drug to define all of the events that occur in the first few minutes to several days of drug treatment to establish that inhibition of this new cancer gene is a viable therapeutic strategy. This grant is generously supported by Rachael Chaffin’s Research Fund, a Hero Fund created in memory of a young girl who loved life. Rachael loved people, animals and the outdoors. It was heartbreaking when she was diagnosed with Rhabdomyosarcoma in the summer of 2013 at the age of 11. With a positive attitude and determination, Rachael began her long battle with cancer. She truly believed she would beat cancer so she could go on to help others. In 2014, Rachael organized a team of family and friends called “Kicking Cancer with Ray Ray” to raise funds for St. Baldrick’s and they continue the tradition today. This Hero Fund honors Rachael’s passion to find a cure for kids’ cancer and carries on her legacy of increasing awareness of childhood cancer to find better treatment options and cures through research.

Dr. Resnick's research project focuses on how to cure one of the deadliest brain tumors in children called diffuse midline gliomas (DMGs), previously also known as diffuse intrinsic pontine gliomas (DIPGs). No available cancer treatments work against DMGs and children die from this lethal disease within 8-11 months of diagnosis. To improve survival and develop better treatment against DMGs, he assessed genes being turned on or off in DMG tumor cells. Together with colleagues, he has identified novel gene products common in multiple DMG tumors that arise when two unrelated genes join and become expressed as one novel protein entity. Here, he will study the role of these gene products, or gene fusions, in DMGs, specifically those involving a known cancer-causing gene called MET. He will test drugs that target the MET gene fusions in DMGs by performing experiments on models that accurately represent human DMG tumors. The results from this project will help identify new drug treatment strategies to target DMG tumors in children. Successful therapy options from this study will be made available to children with DMGs in real-time through our partnership with a clinical trial consortium that brings new treatments to children with brain tumors.

Pediatric high-grade gliomas (pHGGs) are a fatal childhood cancer of the brain. Deregulation of specific histone modifications, both with and without a direct link to specific mutations, have been identified in these tumors. This project will investigate histone H3 post-translational modifications (PTMs) in pHGGs to advance our understanding of tumor development and understanding of biologic characteristics, and to promote the identification of effective therapies for improving the outcomes for patients with these tumors. This grant is generously supported by The Benicio Martinez Fund for Pediatric Cancer Research, a St. Baldrick's Hero Fund created in honor of Benny's fight with cancer and supports cures and better treatments for kids like him. Weeks after being the top fundraiser in his 6th grade class and shaving his head at his school’s event, Benny was diagnosed with medulloblastoma. Since then he has had brain surgery, radiation and chemotherapy. Despite complications from treatment and setbacks, Benny has an amazing can-do attitude and is battling the cancer with courageous determination.

Rhabdomyosarcoma is a common cancer in kids. It can be a very aggressive disease, especially a type that is caused by a genetic change that creates an abnormal cancer-driving protein in the cell, called "P3F". P3F-driven rhabdomyosarcoma shows a strong tendency to spread to other parts of the body, which is what typically leads to death from the disease. P3F is a very hard drug target. However, P3F works together with other machinery in the cell to cause rhabdomyosarcoma. Such machinery could be targeted to interfere with P3F effects, but is not well understood. Dr. Jedlicka and colleagues have recently found new parts of this machinery that help P3F cause rhabdomyosarcoma to spread to other parts of the body. In this project he will better understand how this new machinery works and how it could be targeted to interfere with rhabdomyosarcoma spread. This work could identify new ways to inhibit the aggressive nature of this disease and improve patient outcomes. This grant is generously supported by Marlee’s Smile, a St. Baldrick's partner, founded in honor of 12-year-old, Marlee Pack. Diagnosed with alveolar rhabdomyosarcoma; she relapsed three times in four years. After the final relapse, Marlee had to make a decision no child should have to: continue painful, toxic treatments or enter hospice care. She passed away on February 23, 2019. Our mission at Marlee’s Smile is to change the lives of kids with cancer, one smile at a time in two ways. We give a custom Build-A-Bear to every child fighting cancer, as well as their siblings to honor Marlee’s giving heart as she knew the comfort of a furry friend. We fund targeted research of pediatric cancers, specifically sarcomas to honor Marlee’s dying wish that no child should have to suffer the pain and hopelessness of current cancer treatments.

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.

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.

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.

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 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.

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. 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 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 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.