This grant funds a medical student to complete work in pediatric oncology research for the summer. JMML is a rare type of childhood cancer that is really hard to cure. Right now, even our best treatments only stop this cancer for a year or so before it starts to come back. Cancers can be studied in specific models, which allow researchers to try out different drugs and treatments to see what works. The goal of this project is to use these models to find new treatments for JMML.

Leukemia is the most common form of childhood cancer. While most children with leukemia can be cured, patients whose leukemia comes back after an initial response to therapy are very difficult to treat and often die of their disease. As the Ty Louis Campbell Foundation St. Baldrick's Fellow, Dr. Levinson studies one of the classes of medicines used to treat leukemia called "glucocorticoids" (a type of steroid), in a type of leukemia called T-cell ALL. Though glucocorticoids are usually very good at killing leukemia cells, some patients have been found to not respond (or be "resistant") to glucocorticoids, while others develop resistance over time, making their disease far more difficult to treat. Dr. Levinson's research is focused on understanding how and why such resistance develops in an effort to identify ways to overcome it and, ultimately, increase the percentage of children with T-cell ALL who can survive their disease. This grant is named for the Ty Louis Campbell Foundation, created in memory of Ty Louis Campbell who lost his battle with brain cancer at the age of five. The Foundation seeks less toxic, more effective treatments that are specifically designed for children fighting cancer. Their ultimate mission is to help fund the intelligence and technology that will uncover new ways to cure children with cancer.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Raman spectroscopy (RS) is used to characterize different types of cancer tissue. Usually RS fingerprints are obtained when a slice of cancer tissue is examined under a microscope. With a new design as a portable hand-held RS probe, the St. Baldrick's Foundation Summer Fellow will use the probe to determine RS fingerprints in cancer cell cultures. If successful, the project results could be used to design uses of the probe in the clinic setting to detect cancer cells in blood or other fluids.

Over-expression of HOXA9 protein in acute leukemias, which are cancers of the blood, is associated with worse outcomes. This over-expression occurs in more than 50% of acute myeloid leukemia (AML) cases and in approximately 75% of infant acute lymphoblastic leukemia (ALL) cases. In the laboratory setting, decreasing the level of HOXA9 in AML cells has been shown to reduce their growth. This project aims to develop a way to target HOXA9 in AML and infant ALL using short segments of DNA called oligonucleotides designed to decrease HOXA9 protein or prevent its function. The use of oligonucleotides as drugs has recently been successful in the treatment of various disorders. The goal of these studies is to eventually lead to the use of oligonucleotides as novel therapeutic agents in a clinical trial setting for treatment of AML and infant ALL.

Brainstem gliomas are deadly brain tumors that affect children. The only effective treatment is radiation therapy, but despite this treatment all children with this disease eventually experience growth of the tumor and eventually death. This research will test if treatments that enhance the efficacy of radiation therapy can improve survival in the laboratory. his could lead to new clinical trials aimed at helping children with brainstem gliomas to survive longer.

Bone marrow transplantation is a highly effective treatment for relapsed and difficult to treat forms of pediatric leukemia, but unfortunately has a high risk for dangerous side effects. Viral infections are a major problem in the weeks and months after bone marrow transplant while children's immune systems are still immature. These infections can be debilitating and even deadly while also being very difficult to treat since available antiviral medications frequently do not work. Over the last few years, researchers have had great success in combating these viral infections by taking T-cells (a type of infection fighting cell that is part of the immune system) donated by children's personalized stem cell donors and engineering them to attack and kill certain viruses. Additionally, the rates of side effects using this therapy have been incredibly low. Dr. Rubinstein now intends to offer this therapy as a preventative measure, with the hope that this strategy will decrease the number of patients suffering from dangerous viral infections after bone marrow transplant. This clinical trial has the potential to decrease the number of pediatric cancer survivors who die from infection while also shortening hospitalizations and decreasing the need for other anti-viral medications.

There are new cancer therapies in which a patient's own immune system is retrained to fight against their cancer. In one of these therapies, known as CAR-T cells, a patient's immune cells are removed from the bloodstream and reprogrammed to target and attack their cancer when the cells are returned to the body. While this therapy has shown great promise, there are still situations, especially with very high-risk cancers, where it does not work. One significant issue that exists with this treatment is that the retrained immune cells do not always stick around after being given back to the patient, which allows the cancer to outlast the therapy and come back. We know that once cancers have resisted a treatment once, it is difficult to use the same treatment again. This projects aims to find ways to alter tumor-targeting immune cells to make them last longer when they are given back to patients, ultimately allowing for a long-term cure for their cancer without the need for further treatment.

Most children diagnosed with cancer today will survive but will develop late complications of their cancer treatment. Childhood cancer survivors have almost twice the risk of diabetes compared to other adults. Diabetes is known to increase the risk of heart disease among survivors, and heart disease is the leading cause of non-cancer death among survivors. Prediabetes is easily diagnosed and begins months to years before diabetes. However, little is known about prediabetes risk-factors and prevention in survivors, despite reports that up to 1 in 3 survivors have prediabetes. Using treatment information and recent assessment of over 3,500 adult survivors of childhood cancer, this research will identify the extent of prediabetes among survivors, characterize what cancer-treatments increase risk, and determine how quickly these survivors develop diabetes. Research will then establish if a medication and lifestyle intervention to prevent diabetes in prediabetic survivors is safe and achievable. This will inform a future diabetes intervention trial with the goal of improving long-term survival and quality of life for childhood cancer survivors.

Acute myeloid leukemia (AML) is the second most common blood cancer in children and is difficult to cure. About one quarter of children with AML have a form of the disease called core binding factor (CBF) AML. Despite intense therapy, cancer will come back in one out of three children with CBF-AML. We want to find new ways to treat this common form of AML by learning how the specific combination of mutations in the cancer cells affect their ability to grow and survive. Some patients with CBF-AML have unique mutations that can stop cells from correctly fixing damage, allowing them to grow too quickly. The project will study how these mutations contribute to CBF-AML cells' development, growth, and survival, affecting the cancer cells' ability to grow using cancer cells with these unique mutations. This will help in understanding how this type of AML develops, and may lead to new ways to treat children with this disease.

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 with aggressive neuroblastoma have poor cure rates despite intensive treatment, and new therapies are needed. Treatments that inhibit important proteins and pathways in neuroblastoma tumors are likely to be more effective with fewer side effects. Kinases are proteins that control signals in cancer cells, leading to cancer cell growth and spread. This study proposes to test a certain inhibitor to determine its effectiveness against neuroblastoma cells and tumors. The results of these studies will determine whether BLU-667 is effective against neuroblastoma, potentially leading to clinical trials using BLU-667 for treatment of children with neuroblastoma.

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 funds an undergraduate student and medical student to complete work in pediatric oncology research for the summer. T-cell acute lymphoblastic leukemia is a deadly childhood cancer that affects blood cells. The current treatment uses highly toxic medications. The goal of the proposed project is to test the efficacy of a novel, less toxic, targeted treatment for T-cell acute lymphoblastic leukemia. This award will train the student to perform experiments to test the efficacy of the novel treatment in T-cell leukemia and to determine the mechanisms of drug action against leukemia cells.

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 a student to complete work in pediatric oncology research for the summer. This lab specializes in harnessing the power of a particular type of immune cells called macrophages and microglia which are the body's scavengers. This is done by blocking a "don't eat me" signal called CD47. The CD47 protein acts as a "don't eat me" signal to macrophages which normally engulf and devour cancer cells and other diseased and dying cells. It turns out that nearly every kind of cancer uses CD47 to evade these macrophages. Covering up the CD47 a "don't eat me" protein allows the immune cells to find and swallow cancer cells. Here we will test whether the ability of macrophages to eat tumor cells can be increased by blocking another immune dampening molecule called adenosine which is rapidly increased by tumor cells as they grow.

This grant funds a student to complete work in pediatric oncology research for the summer. Osteosarcoma (OS) is the most common and highly lethal bone cancer affecting children and adolescent populations. New therapies are desperately needed for this highly aggressive disease, as outcome for metastatic OS has not improved over the past few decades despite the utilization of aggressive combination chemotherapy. The summer fellow will focus on testing a novel CA-IX small molecule inhibitor using syngeneic OS tumors in vitro and in vivo. Activities generated through this Summer Fellowship grant will lay the foundation for pre-clinical data for the use of CA-IX inhibitor in future clinical trials.

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 funds a medical student to complete work in pediatric oncology research for the summer. Pediatric glioblastoma (p-GBM) is a lethal brain tumor that can affect children. This cancer is difficult to treat due to several factors, including the tumor's resistance to conventional therapies as well as the sensitivity of the surrounding healthy brain tissue. Children who undergo surgery to remove the brain tumor live an additional three to six years on average, though the quality of life may be low. Phosphoinositide 3-kinase (PI3K) is a protein family that normally regulates cell replication and survival. However, when it functions incorrectly, cells can experience unchecked growth and cause cancer. Inhibiting this protein family is a viable treatment option for cancer but blocking the whole PI3K family has severe side effects. It is imperative to understand each member of the PI3K family to better develop treatments that involve them.