Grants Search Results

Mixed Phenotype Acute Leukemia (MPAL) is a subtype of leukemia that shares features of the 2 most common types of leukemia: acute myeloblastic leukemia and acute lymphoblastic leukemia. Unfortunately, it is really hard to cure with no consensus treatment. When cells divide, chromosomes can break and the pieces can re-attach to the wrong place resulting in a chromosomal translocation. This new abnormal chromosome can result in the expression of a new gene and a new protein, called a "fusion protein". In MPAL, a common translocation involves the ZNF384 gene that can be fused to over 20 new genes, but the consequences are not well understood. Dr Libbrecht has identified that a novel drug that inhibits BRM/BRG1, essential proteins that maintain the DNA structure, and can kill MPAL cells in vitro. Her studies aim to better understand how BRM/BRG1 inhibition affects the ZNF384 fusion proteins and MPAL cells to validate it as novel therapy for MPAL.

This grant funds a student to complete work in pediatric oncology research for the summer. Dr. Satake and colleagues are studying a rare and aggressive childhood kidney cancer called malignant rhabdoid tumor of the kidney (RTK). Children with RTK have extremely poor outcomes (survival rate 25%) despite lots of different treatments since tumors continue to grow even with treatment and tend to relapse. They believe that the investigational drug called OTS964 may be a new potential treatment. They also believe that OTS964 may be even more effective when used with navitoclax, a drug which has a different mechanism of killing cancer cells. In this project They plan to test the new treatment using these drugs in a human RTK mouse model, and to study the mechanism of actions, with the goal of finding a new treatment for RTK patients. This work is being completed under the mentorship of Dr. Noriko Satake.

Teens with leukemia go through tough treatments that make them feel tired and weak, so they spend a lot of time sitting and lying down, which can make side effects worse and put them at risk for chronic diseases like diabetes. Dr. Ivory is testing ReSeT, a program she developed for teenagers getting leukemia treatment to interrupt sitting time with short exercise breaks that will likely improve their lifestyles, heart health, and quality of life. Over 10 weeks, each teenager will use a Fitbit, health coaching, and an app-based support group to slowly increase their activity. After testing ReSeT in 30 teenagers to see if they can do it and what they think, she will fine-tune ReSeT and test it again in 10 more teenagers and compare how they do with 10 teenagers who didn't get the program to see if the program works. The goal is to use small behavior changes to help teenagers with cancer be more active during and after treatment to improve their lifelong health.

Acute myeloid leukemia (AML) is harder to cure than most other types of childhood leukemia and lymphoma. Treatments are toxic and require patients and their families to spend up to a year in the hospital. Childhood AML survivors often have serious side effects later in life from their treatment. We need new treatments for AML that are less toxic and more effective. AML is often caused by mutations in a protein called N-Ras that tell the leukemia to grow and divide much more quickly than healthy tissue. If we could shut down this abnormal N-Ras signaling, it would stop the leukemia from growing. Unfortunately, no approved drugs exist that target mutant N-Ras proteins. Dr. Decker and his colleagues are testing a new drug called ABD778 that selectively blocks the growth of AML cells with mutant N-Ras. The results of this research could move drugs like ABD778 closer to the clinic and pave the way for new treatments for childhood AML.

Dr. Lerman is studying the connection between how aggressive childhood brain tumors called diffuse midline gliomas (DMGs) look on MRI scans and the DNA of the tumors themselves. Tumors that look different from each other on MRI scans and have different changes in their DNA grow in different ways. What is not known is how the appearance of the tumor on the MRI scan is related to the changes in the tumor's DNA. By studying this connection, Dr. Lerman hopes to predict how a tumor might grow based only on an MRI scan, which would help patients and families who either cannot or choose not to have a surgical procedure called a biopsy to test the tumor's DNA. Right now, there is no treatment that cures DMG and all patients are treated the same way: with radiation. Dr. Lerman plans to identify groups of tumors that behave similarly, which will help future clinical trials test the right medicine for the right patient.

Dr. Dionysiou and team are studying a small molecule naturally found in the body called miR-21. This molecule could make a treatment called allogeneic hematopoietic cell transplantation (allo-HCT), which cures children with aggressive leukemia, safer and more effective. This treatment uses immune cells from a donor, but it can cause a serious problem called graft-versus-host disease (GVHD), where the donor cells attack the patient's healthy tissues. The challenge is to stop this attack without weakening the donor cells' ability to fight the cancer. By understanding how miR-21 controls the immune response, Dr. Dionysiou hopes to find ways to prevent GVHD while allowing the donor cells to attack the cancer, making this life-saving treatment safer and more effective.

In the past decade, new therapies that train the immune system to recognize and kill cancer cells have revolutionized cancer care. Unfortunately, cancers arising from connective tissue like bone have not responded to these immunotherapies. Despite almost four decades of trialing/testing progressively more intensive chemotherapy, outcomes for osteosarcoma (the most common bone tumor) remain dismal once it has spread beyond the initial site. Dr. Smith wants to understand why these immunotherapies have failed by studying a model closely resembling human osteosarcoma. Based on his findings, Dr. Smith will test novel immunotherapies to prioritize the next generation of osteosarcoma human clinical trials.

This grant funds a student to complete work in pediatric oncology research for the summer. B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, affecting over 3,000 children in the U.S. annually. A groundbreaking treatment called CAR T-cell therapy involves collecting a patient's immune cells, engineering them to recognize and kill cancer cells, and reinfusing them into the patient. While effective for many, CAR T-cell therapy often fails over time because the engineered cells can "burn out" or cancer cells change to avoid detection. To solve these problems, Dr. Pulsipher's lab is developing a smarter CAR T-cell system that uses multiple signals to activate, reducing burnout, and targets more than one cancer marker, making it harder for the cancer to hide. If successful, this approach could significantly reduce relapses in B-ALL patients, offering them a better chance at long-term remission. This work is being completed under the mentorship of Dr. Michael Pulsipher.

This grant funds a student to complete work in pediatric oncology research for the summer. Currently, developing a cancer drug in the lab and bringing it to the clinic takes years or even decades to accomplish. Although many initial drugs are promising candidates, they ultimately fail because they have no effect, off-target effects, or are simply too toxic. One exciting avenue for cancer treatment involves modifying a patient's immune cells by adding chimeric antigen receptors (CARs) to their surface. Peptide-centric CARs (PC-CARs) can recognize protein fragments called peptides on the surface of cancer cells, which originate from cancer proteins within. Dr. Yarmarkovich's laboratory has developed PC-CARs against one of the most common childhood cancers called neuroblastoma and is currently pursuing clinical trials. To rapidly develop new PC-CARs, they have used new advancements in artificial intelligence to redesign their PC-CARs to recognize another upregulated neuroblastoma peptide called CHRNA3. Eventually, their research can be expanded to treating all cancers alike. This work is being completed under the mentorship of Dr. Mark Yarmarkovich.

This grant funds a student to complete work in pediatric oncology research for the summer. The Kohanbash lab is investigating how B cells, a critical part of the immune system, function in aggressive brain tumors in children. B cells produce antibodies to fight infections or cancer and carry unique surface markers called B cell receptors, which help them recognize and respond to specific threats. However, in cancer, B cells may behave unpredictably, sometimes helping the body fight against tumors, but in other cases, supporting tumor growth. By examining the specific features of B cell receptors in pediatric high-grade gliomas, they aim to better understand how these immune cells influence tumor development and progression. The goal of this project is to learn more about how the immune system responds to brain tumors in children and how altering these responses could lead to more effective treatments. Ultimately, this research hopes to improve therapies and outcomes for children diagnosed with deadly brain tumors, offering them better chances for recovery and long-term well-being. This work is being completed under the mentorship of Dr. Gary Kohanbash.

This grant funds a student to complete work in pediatric oncology research for the summer. Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma in the United States, with approximately 400 new cases annually. Outcomes for high-risk RMS remain dismal, with three-year event-free survival rates as low as 20-30%. There is an urgent need for innovative therapeutic strategies that are more precise, have less toxicity and have significantly improved efficacy and survival benefits. A subset of RMS tumors have mutations in the RAS gene family, therefore, exploiting these mutations as therapeutic targets is an attractive and targeted therapeutic strategy. Dr. Ladanyi's research aims to test a recently developed RAS inhibitor (RMC-6236) in preclinical patient-derived disease models harboring mutations in RAS. This agent is in clinical trials for adult cancers with some RAS mutations. The St. Baldrick's Foundation Summer Fellow will help to generate the preclinical data necessary for a Phase 1 clinical trial testing RMC-6236 in children with RAS-driven RMS. This work is being completed under the mentorship of Dr. Marc Ladanyi.

This grant funds a student to complete work in pediatric oncology research for the summer. Neuroblastoma, medulloblastoma, rhabdomyosarcoma, and desmoplastic small round cell tumors overexpress human epidermal growth factor receptor II (HER2) and cluster of differentiation (CD24) on their surface. Radioimmunotherapy targets those antigens using antibodies. Radioisotopes bound to those antibodies kill the cells. Radioimmunotherapy causes toxicity to normal tissues. Two step pre-targeted radioimmunotherapy reduces this by allowing excess antibody to clear from normal tissues before radiation is delivered. This is further optimized by the self-assembling and disassembling (SADA) antibody platform. Antibodies aggregate within the tumor and disperse outside of the tumor. Therefore, antibodies bound to the tumor remain in the body longer while excess antibodies are cleared faster. This study will compare two-step pretargeted radioimmunotherapy with the SADA platform to one-step radioimmunotherapy against tumors with HER2/CD24 via laboratory testing and a model study. This work is being completed under the mentorship of Dr. Nai-Kong Cheung.

This grant funds a student to complete work in pediatric oncology research for the summer. Infant acute lymphoblastic leukemia (ALL) is a fast-growing blood cancer often caused by changes in the KMT2A gene, which helps leukemia cells survive and spread. This gene creates harmful fusion proteins that work with a partner protein called menin to keep the cancer growing. New drugs like Revumenib block menin and have shown promise in adults, and a clinical trial is testing whether they can help infants whose leukemia has returned or resisted treatment. To better understand how the drug works, Dr. Ernst and her team are developing a novel B-cell acute leukemia model to study the disease more closely. This model allows them to compare what happens when menin is completely removed versus when it is only blocked by the drug. By studying these cancer cells using advanced gene analysis, they hope to find differences that explain why some cases resist treatment. This research could help doctors use menin-blocking drugs more effectively for infants with aggressive leukemia. This work is being completed under the mentorship of Dr. Patricia Ernst.

This grant funds a student to complete work in pediatric oncology research for the summer. Children diagnosed with diffuse midline glioma (DMG), an aggressive brain tumor, face limited treatment options. A new drug called ONC201 has decreased tumor growth in some patients but not others. This research aims to understand why this difference in response occurs. Researchers have discovered that ONC201 affects how cells modify their genetic instructions (RNA), specifically through a process called m6A modification, which affects thousands of genes. When treating tumor cells with ONC201, this group observed a significant decrease in these modifications. The St. Baldrick's Foundation Summer Fellow plans to help study whether this change happens in all tumor cells or only in those that do not respond well to the drug. By analyzing these samples, they hope to identify markers that could predict which patients will benefit most from this treatment. This knowledge could lead to more effective ways to use ONC201 and help develop better treatments for children with DMG. This work is being completed under the mentorship of Dr. Jessica Foster.

This grant funds a student to complete work in pediatric oncology research for the summer. This project aims to discover new therapies for an aggressive childhood blood cancer (leukemia). They will focus on KMT2A-r leukemia, which is caused by an abnormal fusion protein involving KMT2A and another protein. This fusion protein activates genes that cause leukemia. Unfortunately, KMT2A-r leukemia is refractory to therapy and therefore highly lethal in infants and children. Prior work identified drugs to block proteins that "partner" with the KMT2A-r fusion proteins, including a protein called menin. While this groundbreaking work led to the recent FDA-approval of a new drug, called revumenib, the leukemic cells often develop the capacity to resist the effects of this drug. This projects therefore proposes a novel approach by focusing on HMGA1 proteins as "molecular keys" required by KMT2A-r fusions to "unlock" the genome and activate genes that allow leukemic cells to resist therapy. The St. Baldrick's Foundation Summer Fellow will help test drugs to block HMGA1 function as new therapies for childhood KMT2A-r leukemia. This work is being completed under the mentorship of Dr. Linda Resar.

This grant funds a student to complete work in pediatric oncology research for the summer. Children with aggressive neuroblastoma tumors have poor cure rates despite intensive treatment, and new therapies are needed. Kinases are proteins that control signals in cancer cells leading to cancer cell growth and spread, and we have developed a new drug, getretinib, that inhibits the RET kinase that is important for neuroblastoma tumor growth. This project will test getretinib to determine its effectiveness against neuroblastoma cells and tumors, and evaluate cells before and after treatment with getretinib to determine how getretinib kills neuroblastoma cells and to identify specific genes and proteins that are important for neuroblastoma cell responses and resistance. The results of these studies will determine whether and why getretinib is effective against neuroblastoma, leading to clinical trials using new drugs directed against RET for treatment of children with neuroblastoma. This work is being completed under the mentorship of Dr. Pete Zage.

This grant funds a student to complete work in pediatric oncology research for the summer. The Min and Koschmann groups are developing a new blood test to help doctors track how well treatments are working for children with DIPG, a deadly brain tumor with no cure. Currently, doctors rely on MRI scans, which don't provide enough detail about whether a treatment is effective. This new test will use tiny particles released by tumors, called extracellular vesicles, to offer a simple, non-invasive way to monitor treatment response in real time. If successful, this approach could improve treatment decisions and be adapted for other childhood cancers. This work is being completed under the mentorship of Dr. Jouha Min.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The St. Baldrick's Foundation Summer Fellow in the Goldsmith Laboratory at Emory University is working to develop new cell-based immunotherapies for neuroblastoma. They work alongside a team of researchers seeking to apply the unique properties of gamma delta T cells as an effective, off-the-shelf adoptive cell therapy for children with neuroblastoma. During the summer fellowship with St. Baldrick's Foundation, the student will investigate the expansion and anti-neuroblastoma activity of a specific type of gamma delta T cell called the VD1 subset. This work is being completed under the mentorship of Dr. Kelly Goldsmith.

This grant funds a student to complete work in pediatric oncology research for the summer. Childhood brain tumors like Diffuse Intrinsic Pontine Glioma (DIPG) are difficult to treat, especially when they have mutations in a gene called TP53. These mutations make cancer cells resistant to radiation, which is the main treatment for DIPG. With support from the St. Baldrick's Foundation, the summer student researcher is working with Dr. Blackburn's team to study whether existing drugs can help radiation work better in TP53-mutant tumors. Using zebrafish, they have identified several promising drugs and will now investigate how they make cancer cells more vulnerable to treatment. This research could help lead to better therapies for children with DIPG. This work is being completed under the mentorship of Dr. Jessica Blackburn.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Osteosarcoma is a rare and aggressive bone cancer that affects mostly children and older adults. For decades, effective therapies to treat this disease have been lacking, including novel immunotherapy treatments used for other cancers. To understand this failure, it is necessary to study the interaction between the immune system and the tumor itself. As such, the St. Baldrick's Foundation Summer Fellow has developed a tool to measure the activity of the immune system as the tumor progresses. In this system, cancer cells targeted by the immune system will turn green when visualized under a fluorescent microscopic. This tool will help us understand the behavior of effector T lymphocytes, a key cell population in the human body responsible to kill cancer cells and other foreign cells. As such, this summer project will help us understand unique characteristics of this tumor and accelerate the cause for more effective therapies. This work is being completed under the mentorship of Dr. Tyler Jacks.