Grants Search Results

Diffuse Intrinsic Pontine Gliomas (DIPGs) comprise the most lethal pediatric cancers, being almost completely unresponsive to chemotherapy and intractable for surgical removal. Dr. Reinberg and colleagues found that DIPG cells have an unusual "epigenetic signature" that contributes to their malignancy and have also identified the function of proteins that specifically recognize and translate this epigenetic feature. They are working on a novel therapeutic intervention for DIPGs that entails the identification/generation of reagents that specifically inhibit these proteins from functioning at this DIPG-associated epigenetic signature.

This grant is named for the Making Headway Foundation, a St. Baldrick's partner, whose mission for the past 20 years has been to provide care and comfort for children with brain and spinal cord tumors. The Foundation provides a continuum of services and programs while also funding medical research geared to better treatments and a cure.

Pediatric acute leukemias are aggressive blood cancers that result in many childhood cancer deaths despite intensive treatments. Because these leukemias are highly sensitive to radiation, researchers have developed a technology called radioimmunotherapy. Radioimmunotherapy uses antibodies to deliver a radiation payload directly to cancer cells. Most existing radioimmunotherapies are directed against two cell surface proteins called CD33 or CD45. However, because these proteins are also found on many normal blood cells, the amount of radioimmunotherapy that can be safely given via CD33 or CD45 antibodies is limited.

As the recipient of the Emily Beazley's Kures for Kids Fund St. Baldrick's Research Grant, Dr. Walter is developing and rigorously testing a new form of radioimmunotherapy that is directed against CD123. CD123 is found on only a few normal blood cells but is heavily expressed on leukemia cells in most children with acute leukemia. Moreover, CD123 is particularly attractive as a target as it is widely overexpressed on underlying leukemic stem cells (the rare cells that have the ability to generate and fuel these cancers), whereas normal blood stem cells express little or no CD123. These studies are the first to test the value of CD123-targeting radioimmunotherapy and will guide researchers towards bringing this new, less toxic treatment to pediatric patients. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma. Her cancer was extremely aggressive, and she bravely battled it through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle. She inspired a community to come together to show love and changed lives with her message: “You gotta stay strong, you gotta stay positive, no matter what happens.” Emily passed away in 2015 at age of 12. She often talked about her dream of starting a foundation that funded research. She named it “Kures for Kids”. Her family and friends carry on her dream and her mission with this Hero Fund.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Although most children and adolescents are cured with modern treatments, relapsed/refractory ALL remains one of the most common causes of death from pediatric cancer. This observation highlights the importance of understanding why the leukemia cells of some children are difficult to kill with modern drugs (this is called intrinsic resistance). Glucocorticoids are a type of drug that have been used to treat ALL for over 50 years and are given to all children with ALL. It is known that it is harder to cure children with ALL when their leukemia cells show intrinsic resistance to glucocorticoids. He is now working to understand how IL7 makes ALL cells resistant to glucocorticoid drugs and to use this knowledge to develop ways to cure more patients. He has identified drugs that appear to suppress the effects of IL7 on ALL cells and that make them more sensitive to glucocorticoids. They believe that combining one of these drugs with glucocorticoids could cure more children with ALL in the future.

Dr. French is studying one of the most deadly childhood and adolescent cancers known, called NUT midline carcinoma. There is no effective treatment for this cancer, which has a median survival of 6.7 months. Recently, his team discovered a new class of drug, called 'NEO', that in preliminary studies appears promising in models, an unprecedented finding that gives some hope that they may have stumbled across a new effective treatment for this disease. Based on some recent studies, Dr. French thinks that the drug class directly acts against the cancer protein that drives NUT midline carcinoma, called BRD4-NUT. BRD4-NUT is created by a mutation that fuses one gene, BRD4, to another, NUT, which alone don't cause cancer, but when fused together create a very potent cancer protein. He think the drug inhibits both the BRD4 and NUT halves of this fusion in a manner that gives the drug some selectivity for BRD4-NUT. The findings are exciting because the NEO drugs are set for clinical trials to begin in 2019. Dr. French and colleagues are working to 1) validate the findings that the NEO drugs work well in models bearing NUT midline carcinoma to provide rationale to enroll NUT midline carcinoma patients onto these trials, and 2) determine scientifically how the NEO drugs inhibit NUT midline carcinoma growth.

Rhabdomyosarcoma (RMS) is a rare and devastating cancer of childhood. Identifying and characterizing novel genes essential for RMS cancer growth can help improve our understanding of RMS disease process. Novel genes identified can also serve as potential therapeutic drug targets for treating RMS patients. BCOR is among the most frequently mutated genes in RMS. However, the role of BCOR in promoting cancer growth and disease progression remains unexplored. As the recipient of the Glen Parker Bayne Hero Fund St. Baldrick's Research Grant, Dr. Chen is working to characterize the biological function of BCOR in RMS. Completion of the study will not only provide new insights into the role of BCOR in the disease process of RMS, but also therapeutic rationale for targeting BCOR in improving survival outcomes of RMS patients.

This grant is named for the Glen Parker Bayne Hero Fund which was established to honor this little boy's courageous battle with rhabdomyosarcoma and celebrate his survivorship. Glen was diagnosed when he was almost 2 and endured a year of intensive treatment. Today he has no evidence of disease and Glen's Army, a group of family and friends rally to raise funds and awareness for research to find cures.

Cancer remains a major cause of death in children. It is still difficult to collect and share large samples of clinical trials data across research groups, because everyone collects the data according to their own preferences and definitions. This limits researchers' ability to use a patients' clinical data and to match it to data from new techniques, like genomic testing, to make discoveries. The Pediatric Cancer Data Commons (PCDC) designs better ways to collect and store these clinical data and to connect these data to other types of data, such as imaging data (x-rays, CT scans) and genomic data, by developing and documenting a common language and standards. This allows others to see how our researchers are collecting, storing, sharing, and using clinical trials data so that others can also conduct research in the same way and then easily share and compare data sets across the world. The PCDC Consortium members are dedicated to gathering as much data as possible from around the world into a "data commons" - a single place where researchers everywhere can go to access these data so that they can explore the data and select the subsets of data that are useful for answering their research questions. Fund administered by The University of Chicago.

Based on progress to date, Dr. Ou was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Due to the tumor and treatment damaging the developing brain, 60-80% of pediatric brain tumor survivors experience long-term neurocognitive impairment. There are two possible paths to improve outcomes: intervene the adverse brain development after treatment, or further optimize radiotherapy dose distribution in the brain before treatment. For the former, the question is to find at-risk patients to intervene after treatment. For the latter, the question is to find target brain regions, where changing radiation doses can potentially change outcomes. Both questions have been studied on the population-level, not on the individual level. This project aims to push our knowledge in these two fronts to the individual level. Dr. Ou is using data from 3 just finished clinical trials to find target patients and find target brain regions for radiation dose optimization. Compared to studies that consider one risk factor a time, Dr. Ou will consider a comprehensive set of risk factors to improve precision to the individual level. The results will allow him to design future larger-scale, multi-site retrospective replicative and eventually prospective clinical trials, to improve neurocognitive outcomes in this vulnerable population before and after treatment.

This grant is generously supported by the Grace for Good Fund, established in honor of Grace Carey and celebrates her survivorship from medulloblastoma. Her cancer journey began in 2007 when she was diagnosed at age 5 with a treatment regime that entailed surgery, proton beam therapy and chemotherapy. While Grace handled it all with minor setbacks, she now faces the physical, emotional and cognitive challenges wrought by the very medications and procedures that saved her life. This fund was inspired by Grace’s desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

Based on progress to date, Dr. Stanton was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant.
Rhabdomyosarcoma (RMS) is a highly aggressive and lethal pediatric cancer affecting children and adolescents and arises in the soft tissue and skeletal muscle of the extremities, head and neck, and reproductive organs. From the clinical perspective, although patient outcomes have improved in general, nevertheless survival rates for some RMS tumors remains at less than 30%. One particularly aggressive subtype is alveolar RMS which is driven by the occurrence of chromosomal translocations resulting in the generation of chimeric or fusion proteins between the PAX3 or PAX7 and the FOXO1 genes. These are known as fusion-positive RMS (FP-RMS) and are associated with reduced relapse-free survival and generally poorer outcomes. But researchers still have limited understanding of how the "fusion" gene itself is driving the tumor, and no subtype-specific therapies exist. Dr. Stanton aims to determine how the fusion gene works with a protein complex known as BAF, to alter the epigenetic state of the cell to keep them dividing and stop the cell from differentiating into mature muscle tissue. His team is exploring the mechanism of how the BAF complex regulates the epigenetic state and memory of the FP-RMS. Furthermore, using small-molecule drugs and genetic depletion strategies (CRISPR) they will determine if FP-RMS tumors are dependent on the BAF complex for survival. Finally, they are working to identify potential novel therapies for patients with aggressive and lethal FP-RMS, to improve their outcome.

The 2021 and 2022 portions of this grant is funded by and named for the Aiden's Army Fund. When he was 8 years old, Aiden Binkley was diagnosed with Stage IV rhabdomyosarcoma. He had a huge tumor in his pelvis and the cancer had metastasized to his lungs. But this bright, funny and courageous boy believed he got cancer so he could grow up to find a cure for it. Aiden’s story has inspired so many people and his vision to cure cancer is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

The 2020 and 2023 portions of this grant is funded by and named for by Berry Strong, a St. Baldrick’s Hero Fund, established in honor of Caroline Berry. Diagnosed with alveolar rhabdomyosarcoma when she was 14, Caroline endured a two-year battle with courage and determination. Throughout treatments of radiation and chemotherapy and undergoing six surgeries, Caroline was a beacon of hope, unselfishly raising awareness and funding for research so no child would have to endure what she did. After a brief remission, scans revealed Caroline had relapsed and she passed away on Thanksgiving in 2018. Caroline is remembered as a bright light, creative, intelligent, funny and feisty who was always eager to share a smile with others. She continues to be an inspiration through the Berry Strong Hero Fund which will continue her legacy and her passion to raise awareness and fund the most promising childhood cancer research.

There is a type of leukemia which occurs mainly in infants, but also in children who have previously received chemotherapy for an unrelated cancer. This type of leukemia is extremely difficult to treat and often comes back despite chemotherapy. We have evidence that this leukemia relies on a protein called MBNL1. By disrupting MBNL1, leukemia cells cannot produce specific proteins they need to grow. As the Julia's Legacy of Hope St. Baldrick's Scholar, Dr. Lee, as proof of concept, has shown that MBNL1 can be blocked by a chemical inhibitor. By using computer models, testing large libraries of drug-like chemicals, and applying special chemistry techniques to improve how effective a drug is, Dr. Lee is looking for a way to block MBNL1 with a drug that can be used in humans. This will lead to a new therapy for this class of leukemias.

A portion of this grant is named for Julia's Legacy of Hope, a 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.

Surviving cancer is an achievement of immeasurable magnitude, however for most survivors this achievement does not signify the end of cancer related health issues. The cardiovascular system is commonly affected by cancer treatment and cardiovascular disease is the second leading cause of death in childhood cancer survivors. As the To-morrow's Research Fund St. Baldrick's Scholar, Dr. Bottinor is helping childhood cancer survivors live healthier lives by using advanced cardiac imaging techniques to identify survivors with subclinical cardiovascular dysfunction before they develop overt heart disease. She plans to use echocardiographic imaging to detect cardiovascular disease at its earliest stages, when treatment is most likely to be efficacious.

Dr. Bottinor is analyzing cardiac screening studies collected in routine care to determine if subclinical abnormalities can predict which survivors are at risk for subsequent cardiovascular disease and therefore the most likely to benefit from early medical intervention. She believes these techniques will be helpful in childhood cancer survivors because previous work in adult patients has suggested that advanced cardiac imaging techniques can predict which patients with cancer on active treatment are at higher risk for developing subsequent cardiovascular disease.

This grant is named for To-morrow's Research Fund, a Hero Fund created to honor Becky Morrow who is a childhood cancer survivor. Becky was diagnosed with acute lyphoblastic leukemia when she was 12 and endured grueling treatments and its side effects. Today she is cancer free, a wife and a mom but suffers late effects. This fund supports survivorship research for safer treatments that help kids not only survive but thrive.

Awarded at Vanderbilt University and transferred to Virginia Commonwealth University.

Ewing sarcoma is an aggressive bone and soft tissue cancer that primarily affects children and adolescents. Patients often suffer severe side-effects from treatment and there are no second-line therapies for relapsed tumors. It is critical that we develop new and less toxic treatments for this cancer. Ewing Sarcoma is caused by a rearrangement of DNA that fuses pieces of two different proteins together to form a new protein. This new protein, called EWS-FLI1, can turn on genes that should not be on, leading to the transformation of the cell into an Ewing Sarcoma tumor. This fusion protein has features that make it very difficult to study, it sticks to itself and does not have a structure, a good analogy is that it behaves like a piece of cooked spaghetti. As the Shohet Family Fund for Ewing Sarcoma Research St. Baldrick's Scholar, Dr. Libich is utilizing his background in working with similar proteins that do not have structure. He is using NMR (nuclear magnetic resonance) which works just like MRI, to peer into the protein to understand exactly how it functions. This information is critical for designing molecules (drugs) that will be able to only affect the function of EWS-FLI1 and thus open new ways of attacking Ewing's sarcoma.

This grant is funded by and named for the Shohet Family Fund for Ewing Sarcoma Research. In his freshman year of college, Noah was diagnosed with Ewing sarcoma. He endured many months of chemotherapy and had limb salvage surgery. Able to return to school, Noah had no evidence of disease for 2½ years until April 2018 when routine scans revealed he had relapsed. He passed away in May 2021 at the age of 25. Noah and his family were always passionate about the need for curative treatments for diseases of the AYA population. The Shohet family intends to raise funds for this Hero Fund in Noah's memory to find cures for Ewing sarcoma and to carry on his legacy of possibilities and hope.

Survivors of cancer have a higher risk of health problems because of the severity of the chemotherapy and radiation treatments they received. As survivors of childhood cancer age, they increasingly succumb to the "late effects" of their cancer treatment (such as second cancers and heart and lung disease). After 10-15 years, these late effects become the leading causes of death in this population. Adolescents and young adults (AYAs, aged 15-39) are a subgroup of cancer patients that are defined as high risk because they: more commonly suffer from toxicities and side effects of their cancer treatment; have unique barriers to accessing health care; and suffer specific psychosocial concerns because of their life stage transitioning into adulthood. To date, little research has been done on the factors that influence long-term health outcomes in the population of survivors of AYA cancer. Dr. Moke is working to explore how cancer and its treatments affect health later on in life in survivors of AYA cancer, identify the causes of death in this population, and determine what factors and cancer treatments are associated with these specific life threatening health problems. This study will provide the baseline data needed to design ways to decrease the severity of and death from these late effects, and thus be an important step in promoting long and healthy lives in survivors of AYA cancer.

Based on progress to date, Dr. Johnston was awarded a new grant in 2022 to fund an additional year of this Scholar grant. Hospice (home-based end of life care focusing on pain control and emotional support) leads to better quality of life for the dying person and easier grief for families when an adult dies of cancer. We do not know if the same is true in children. We do not know rates of hospice use in children dying of cancer, what inequalities exist, nor how families perceive hospice, especially in minorities. Dr. Johnston aims to better understand US pediatric hospice use with a focus on minorities. Her team will determine rates of and inequities in hospice use in children dying of cancer nationally and then interview families that had a child die of cancer and pediatric oncology and hospice teams to determine if the inequities are in line with child and family preferences. Early palliative care in adults leads to better quality of life and more hospice and home death. It is unknown if the same is true in children with cancer. Dr. Johnston and colleagues will offer early palliative care to children with brain tumors to determine if early palliative care is acceptable to families and providers and if a randomized control trial would be possible. After this project, she will be able to use information and skills gained to design a trial aimed at improving hospice access for those that desire hospice that builds on the lessons learned in this study. Researchers will then better understand hospice in children with cancer, necessary to ensure all children dying of cancer have high quality end of life care.

Based on progress to date, Dr. Velasquez was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Childhood acute myeloid leukemia (AML) is a blood cancer that is very difficult to treat in children and adolescents. T cells are one component of the patient's own immune system that helps defend against infections. New cancer treatments use modified T-cells that can ‘see' and kill cells that have CD123, a molecule present on AML, and have shown promising results in studies in the laboratory. Dr. Velasquez is testing if these specific T-cells are safe and can kill leukemia cells in children that have AML that came back after initial treatment. She also wants to see what happens to these T-cells after they have been given to the patient and how it affects the tumor. This information from the treated patients and the study of their T-cells and tumor cells will be useful in finding a cure for AML.

Osteosarcoma is a cancer of bone that happens in young people. Dr. Davis and colleagues are trying to find ways to help the immune system fight off tumor cells, which may help us find a cure. They are examining all of the different type of immune cells in over 100 osteosarcoma tumor samples to identify how patterns in the cells match with other characteristics, such as how well a patient does with standard osteosarcoma treatment. They are also looking at biopsies from patients before and after immune therapy and will try to boost responses to immune therapy with a targeted drug. By understanding the way the immune system "sees" (or doesn't see) osteosarcoma, they will be able to predict which patients will benefit from different types of immune therapy and who will need other drugs added to their treatment regimen.

A portion of this grant is generously supported by the Sweet Caroline Fund, a St. Baldrick's Hero Fund, created to honor the memory of Caroline Richards who was diagnosed in 2014 with osteosarcoma in her right arm when she was 11 years old. She persevered through rigorous treatments with a giving spirit and a contagious smile, always thinking of how to make others happy or laugh. Caroline sadly lost her battle a year later but this fund pays tribute to her compassion for others by supporting osteosarcoma research to help kids with cancer.

This grant funds a graduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Millions of cells are formed every day in the developing brain of children. Medulloblastoma, a pediatric tumor, occurs when the proliferation of cells in the cerebellum (a lower part of the brain) becomes uncontrolled. The Notch pathway is a key mechanism that governs cell proliferation in many biological contexts. Aberrant up-regulation of Notch signals is associated with medulloblastoma. Re-gaining control of Notch could help cure medulloblastoma patients. The goal of the Rual laboratory is to better understand the molecular mechanisms that control Notch signals in brain cells and, thus, to define novel therapeutic targets for the benefit of medulloblastoma patients. This lab recently identified the L3MBTL3 gene as a new modulator of Notch signals. Importantly, previous studies have shown that the L3MBTL3 genes is deleted in medulloblastoma patients. These researchers hypothesize that the L3MBTL3 deletions observed in medulloblastoma patients result in the aberrant regulation of Notch signals, thus supporting tumorigenesis. In this project, the student is helping to test this hypothesis by studying the extent to which inhibiting L3MBTL3 modulate medulloblastoma tumor progression in models of medulloblastoma.

This grant funds a medical school student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Sarcoma is a type of cancer that arises in the bones, muscle or fat. In children, sarcoma continues to pose a formidable clinical challenge because it is frequently resistant to current treatments (chemotherapy and radiation). This student is helping to test the theory that a cancer-causing gene called ROS1 drives the aggressive growth of some sarcoma tumors. There are already FDA approved ROS1 drugs, and these are effective in adults with ROS1-driven lung cancer. Our overall goal is to validate known cancer causing genes, and repurpose safe drugs so that fewer children succumb to sarcoma, and the survivors have excellent long-term quality of life.

Lymphoma and leukemia are cancers that often strike children. Some types of these cancers cannot grow or survive without a protein called MALT1. As the Do It For Dominic Fund St. Baldrick's Fellow, Dr. Maurer found that, in some lymphoma cells, when the level of another protein called GRK2 was lowered, it led to more action of the MALT1, and more cancer growth. So, she thinks that GRK2 might be working to stop lymphoma tumors by blocking MALT1. She is working to find out two things: Does the level of GRK2 also affect the growth of leukemia? And how exactly does GRK2 interact with MALT1 to block its tumor-growing action? Understanding this interaction will help to design new treatments that work by blocking the MALT1 and stopping the growth of lymphoma cells, and perhaps leukemia cells too, so that children can be cured.

This grant is named for the Do It for Dominic Fund which honors the memory of Dominic Cairo who battled non-Hodgkins lymphoma and was a hero to his school and community. His family and friends continue to raise funds and support research in the hopes that no child has to go through what Dominic endured.

Osteosarcoma (OS) is the most common malignant bone tumor in children, but only five chemotherapy drugs have been shown to be beneficial, and overall survival remains poor (60%). There are no effective standard-of-care therapies for patients who relapse. Identifying new treatment strategies in OS is of paramount importance. Prior studies evaluating the genetic code of OS tumors show significant genetic heterogeneity among patients and have not uncovered recurrent changes that can be successfully targeted. Dr. Pavisic is using computational algorithms established by the Califano laboratory to identify universal tumor dependencies known as master regulator (MR) proteins from the messages expressed by the tumor’s genetic code to make proteins (RNA). Using information from drug studies done in OS cells, she is prioritizing drugs by their ability to reverse the activity of a tumor’s most aberrantly active MR proteins. MR proteins integrate the effects of many genetic alterations and are critical to tumor cell survival, thus represent novel tumor biomarkers and drug targets. Dr. Pavisic hypothesizes that MR analysis in OS will lead to biologically-relevant patient classification and risk stratification, and prioritize new drugs for immediate testing in laboratory models of OS and in clinical trials to improve outcomes for children with OS.

Diffuse midline gliomas (DMGs) are aggressive brain tumors in children that are almost uniformly fatal. Curative surgery is not possible, radiation therapy provides only temporary relief, and chemotherapies have proven wholly ineffective. New, effective therapies are desperately needed for children with these tumors, but decades of clinical trials have so far failed to improve outcomes. Researchers have now identified a specific mutation (H3K27M) that affects how DNA is organized and drives a majority of DMG tumors. This insight has yet to result in new treatment options, however, an emerging understanding suggests that other cellular changes are required for tumors to grow. As the Kids Shouldn't Have Cancer Foundation St. Baldrick's Fellow, Dr. Dahl and colleagues have identified a protein complex called the SEC that DMGs with the H3K27M mutation are dependent on for survival. This complex regulates how DMG cells read their genetic code. An existing class of drugs called CDK9 inhibitors are effective in blocking the activity of the SEC. Dr. Dahl is researching how the SEC acts to promote DMG cell growth and testing whether CDK9 inhibitors can be used to interrupt this process. If successful, this research will provide the rationale for the design of future clinical trials using CDK9 inhibition as a new way of treating this intractable disease.

The Kids Shouldn’t Have Cancer Foundation, a St. Baldrick's partner, was founded after Jon and Kimberly Wade lost their son, Jonny and twin to brother, Jacky to medulloblastoma. He endured countless surgeries and procedures, pain and fatigue yet maintained unshakable faith and grace through it all. As a result, he told his mother, “I don’t want any other kid to have cancer.” Their mission is to honor Jonny’s wish by conquering pediatric brain cancer through research and political action with an emphasis on responsible spending.