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Dr. Kabanov and colleagues propose an entirely new way to treat medulloblastoma, the most common malignant pediatric brain tumor. Current treatment requires radiation followed by a year of chemotherapy, fails almost half the patients, and can leave survivors with lifelong brain injury. Tiny extracellular vesicles called exosomes produced by a type of immune cell called macrophages were discovered to travel from the bloodstream into brain tumors. Dr. Kabanov will load exosomes with an agonist of Toll-like receptor to reprogram medulloblastoma tumor associated myeloid cells and enhance their tumoricidal properties. If successful, the therapy will improve medulloblastoma treatment by replacing the current radiation and chemotherapy with the one that is less toxic and more effective.

The second year of this grant is funded by and named for the Miracles in Memory of 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 first year of this grant is funded by and named for the Strong & Courageous Hero Fund, established in honor of Jonah. It celebrates his survivorship from medulloblastoma and his goofy, loving, inclusive personality. This fund was inspired by Jonah’s desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

Genes instruct cells to do their jobs through making specific proteins. In our body, all cells store this what-to-do manual in a set of higher-order structures called chromosomes. When chromosomes break off, the broken pieces sometimes exchange their places to build new chromosomes. These errors, known as translocations, could have no effect on our bodies, but in many cases they might cause problems as severe as cancer. Dr. Su's research focuses on learning how chromosomal translocations promote tumor formation in children and young adults, as well as looking for clinically useful approaches to correct their pathogenic activities and cure these deadly diseases.

Leukemia, a cancer of the blood and bone marrow, is the most common cancer in kids. Over the last 60 years, great strides have been made in treating children with leukemia, and today, most leukemias are curable. However, certain leukemias are difficult to treat and have a poor prognosis. In order to better treat cancers, researchers seek to better understand the pathways by which cancer cells develop in order to identify medicines that target proteins in these pathways. Dr. Aumann and colleagues study the fusion protein CALM-AF10 which is found in some leukemias, and found that these leukemias have increased expression of a protein called SIX1. Dr. Aumann is studying how the SIX1 protein makes blood cells turn into leukemia cells, and is using two small molecule inhibitors in combination with other chemotherapy as potential new treatments for this and other leukemias. The hope is that the these studies will clarify the role of SIX1 in CALM-AF10 and other leukemias.

Acute Lymphoblastic Leukemia (ALL) are aggressive cancers of B- and T- immune cells. ALL is most common in children but also affects adolescents and young adults. 90% of childhood ALL is curable. However, ~10% of children and ~30% of adolescents and young adults with ALL are not cured. To combat hard-to-treat ALL, Dr. Swaminathan will harness the body’s natural anti-cancer defense mechanism: a type of immune cell called a natural killer (NK) cell. He will also find defective NK cells in children with ALL. Those with fewer defective NK cells tend to survive longer and spend more of their lives free from disease compared to patients with high levels of abnormal NK cells. These findings will inform the development of NK cells as affordable therapies to cure pediatric ALL.

Though most children with cancer are able to be cured, some children are more likely to be cured than others, even with the best available treatments. Childhood cancer treatment is a long and difficult process for children and their families, and most families need support from those around them including community support and resources. Adults with cancer living in disadvantaged communities are much more likely to die from their cancer, though much less is known about how the characteristics of the community impact outcomes for children with cancer. Dr. Hoppmann uses a large national cancer database, coupled with measures of social determinants of health (measures of poverty, healthcare access, educational attainment, social and physical environment) to determine how these community vulnerabilities impact children with cancer. Results will help ensure gains made in pediatric cancer are shared equitably among all children, including those from disadvantaged areas.

Anthracycline chemotherapies are important, lifesaving medicines given to a majority of children with cancer. However, they can injure the heart and cause heart failure in up to 10% of children years later, during cancer survivorship. Unfortunately, with the current available tools, there is not much known about which children will develop heart failure and what treatments would work best for them, and by the time the problem is identified it may be too late to help them. Dr. Narayan seeks to address this problem by using state-of-the-art, in-depth imaging techniques in adolescent and young adult survivors of childhood cancer to detect early changes in the heart. The goal is to develop new tools to provide early, personalized treatments to prevent heart failure.

This grant is named for TEAM ABBY Gives, a St. Baldrick's Hero Fund. Abby was diagnosed with Pre-B ALL when she was almost five years old. She had a successful bone marrow transplant, but battle battled graft vs. host disease (GVHD) and heart disease for years. Abby and her treatment team worked hard over many years to keep the GVHD in check. Sadly, Abby passed away on October 19, 2021. This fund unites the incredible support of family and friends in Abby's memory and inspires others to join the fight for cures and better treatments.

Diffuse intrinsic pontine glioma (DIPG) is a deadly pediatric brain cancer, and there is a dire need to develop new therapeutic strategies to improve the terrible outcomes for these patients. Looking at genes that are turned on or off in a cancer can be helpful to figure out what is causing cancer growth. While looking at genes that are turned on in DIPG, Dr. Tsai found a gene called FOXR2 that is turned on at very high levels in a subset of DIPGs. FOXR2 is usually turned off, and turning on FOXR2 makes tumors grow very quickly. FOXR2 is actually capable of turning on an entire set of genes that are called ETS transcription factors (TFs). This is surprising as these genes have never been shown to be activated in DIPGs. Others have shown that ETS TFs can turn on the MAPK signaling pathway. Dr. Tsai also has found that FOXR2 is able to activate MAPK signaling. The goal is to determine exactly how FOXR2 and ETS TFs cooperate together to turn on MAPK signaling to make DIPGs grow. This grant was awarded at Dana-Farber Cancer Institute and transferred to Children's Hospital of Los Angeles.

A portion of this grant is generously supported by Griffin's Guardians, a St. Baldrick's partner. Griffin's Guardians was created by the Engles in memory of their son, Griffin. Their mission is to provide support and financial assistance to children battling cancer in Central New York, raise awareness about pediatric cancer and provide funding for research.

Relapse continues to be the most common cause of failure after transplantation for childhood leukemia. the Pediatric Blood and Marrow Transplant Consortium (PBMTC) is conducting three trials that will identify children with leukemia undergoing transplantation that are at especially high risk and add a novel immunomodulatory or cellular therapeutic intervention to prevent relapse. Funds administered by the National Marrow Donor Program.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.