Grants Search Results

All proteins in our bodies are made using assembly instructions contained in messenger RNAs, or mRNA. mRNA molecules themselves are constructed from building blocks called exons. When exons are joined together, or 'spliced', out of order, the resulting protein code is scrambled. This is what causes several types of leukemias in older adults. We have discovered that incorrect splicing also occurs with high frequency in childhood leukemias originating in antibody-producing B-cells. Dr. Thomas-Tikhonenko is testing two ideas. The first is that incorrect splicing is needed to sustain uncontrolled multiplication of leukemic cells. The second is that restoring proper exon assembly with specific drugs would slow down or block cancerous growth. If successful, these studies could pave the way to new clinical trials and improved survival of children with leukemia.

Diffuse intrinsic pontine gliomas (DIPG) are lethal pediatric brain tumors with no treatments. In order to develop cures we need to understand their biology. Cancers survive on fuel to generate energy to support their uncontrolled proliferation. One of the fundamental nutrients that drive the energy production is the amino acid glutamine. How glutamine is taken up and metabolized by DIPG tumor cells is not know. Further it is not known if inhibiting cancer cells from taking up and metabolizing this fuel is therapeutic. To address this significant gap in our knowledge, Dr. Venneti is studying glutamine metabolism in DIPG cancer cells and evaluating inhibition of glutamine metabolism as a potential therapeutic strategy. This grant is made with generous support from the McKenna Claire Foundation established by the Wetzel family in memory of their daughter, McKenna. Their mission is to cure pediatric brain cancer by raising awareness, increasing community involvement and funding research.

High grade gliomas (HGG) are a vicious subtype of pediatric brain tumors that remain the leading cause of death among children with cancer. New therapeutic strategies are urgently needed to combat this scourge. By mining genomic datasets from HGGs, Dr. Walensky's team has identified a unique susceptibility profile based on retention of wild-type p53 status and dual expression of the negative regulators HDM2 and HDMX. Whereas p53 can be mutated or deleted to avoid cell cycle arrest or apoptosis, a frequent alternative mode of p53 suppression relies on overexpression of HDM2 and HDMX. Small molecules have been developed to target HDM2 specifically, but co-expression of HDMX causes resistance. Only a stapled peptide modeled after the critical p53 transactivation helix is capable of blocking both HDM2 and HDMX, a feature that has prompted its advancement to Phase I/II clinical trials in adult cancers. As the recipient of the St. Baldrick’s Research Grant with generous support from the Team Campbell Foundation, Dr. Walensky is testing a novel therapeutic strategy for pediatric HGG based on a dual-targeting stapled peptide inhibitor of HDM2/HDMX. He believes that the proof-of-concept data to emerge could provide a compelling rationale for conducting a clinical trial in these otherwise rapidly fatal pediatric brain cancers. The Team Campbell Foundation was created in memory of Campbell Hoyt who passed away from Anaplastic Ependymoma. Their mission is to improve the lives of families facing a childhood cancer diagnosis through raising awareness, funding research and providing psycho-social enrichment opportunities.

Half of neuroblastomas are high-risk neuroblastoma, with poor survival. Understanding abnormalities that drive high-risk neuroblastoma (drivers) enables development of therapies against specific drivers. Until 2015, we had identified drivers for half of high-risk neuroblastomas. Recently, most remaining high-risk neuroblastomas were shown to have high levels of TERT, a protein that helps chromosomes replicate. It is still not clear how a protein that helps chromosomes replicate could drive cancer. Perhaps TERT is needed for neuroblastoma tumors to grow, but is not driving the tumor. To distinguish these possibilities, Dr. Weiss is testing whether TERT can drive neuroblastoma in human stem-cell models. In Dr. Weiss' system, stem cells generated from normal human blood or skin cells, are differentiated to form a cell type called neural crest, from which neuroblastoma is derived. He is introducing known drivers into these cells to generate a model for neuroblastoma. Some known drivers (MYCN) lead to neuroblastoma, while others (ALK) do not. Dr. Weiss is using this model to test whether TERT is a driver, or is required for neuroblastoma in the context of other drivers (ALK). Successful completion will generate a model to evaluate whether therapy directed against TERT could help children with neuroblastoma. This grant is generously supported by the Amanda Rozman Pediatric Cancer Research Fund created in memory of Amanda Rozman and honors her courageous battle with neuroblastoma by funding promising new to improve the efficacy and number of treatments available for relapsed and refractory neuroblastoma.

Cancer cells are hard to defeat because they are so similar to normal cells. Most current methods that kill cancer cells impose collateral damage on normal cells that lead to immune suppression, hair loss, and gastro-intestinal damage. Dr. Whitehurst's research focuses on identifying therapies that will only kill tumor cells but leave normal cells unharmed. Here, she is focused on a tumor type that impacts adolescents: Ewing Sarcoma. She has identified a pathway, called TNFa, which is “mis-wired” in these cancer cells. Instead of dying when this pathway is activated, the cancer cells keep growing. Importantly, she has identified inhibitors of the pathway that can kill these tumor cells. Dr. Whitehurst is working to understand how this pathway is mis-wired in cancer cells and the consequences of its inhibition. The end goal would be the identification of chemical inhibitors that could be used in the clinic as a less toxic and more effective treatment option.

Cancer is a genetic disease in which a cell learns to take advantage of certain processes that allow that cell to grow and survive unchecked. Bone cancer is an aggressive disease in both children and pet dogs that can be painful and often leads to death of the patient even with aggressive surgery and chemotherapy. Most often these patients die because the tumor has spread to other areas of the body, not from the original bone tumor, which is often removed with surgery. Therefore, in order to better battle this disease, new therapies that target the cells that spread are needed. Preliminary work with a new drug that targets this process has shown promise as just such a therapy. The goal of The Ben's Green Drakkoman St. Baldrick's Research Grant is to more thoroughly investigate this drug for its ability to prevent or delay spread of the tumor cells using both human and dog bone tumor cells. This grant is named for the Ben's Green Drakkoman Fund, a St. Baldrick's Hero Fund created to honor the memory of Ben Stowell who battled osteosarcoma with an inspiring determination to live life fully. The fund is named after a super hero Ben created named the Green Drakkoman who defeats his enemy, the Evil Alien.

Rhabdomyosarcoma is a deadly cancer when spread through the body. With the Aiden's Army Fund St. Baldrick's Research Grant, Dr. Li is combining drugs already FDA approved for adult cancers in a way that stops rhabdomyosarcoma tumor cells from creating new tumors elsewhere in the body. This approach is unique because Dr. Li not only aims to stop the tumor cells from growing, but will try to convert what is left to non-cancerous cells similar to what is found in normal muscle. This grant is funded by and named for the Aiden's Army Fund, a St. Baldrick's Hero Fund. Aiden Binkley who was diagnosed with Stage IV rhabdomyosarcoma at age 8. This bright, funny and courageous little boy believed he got cancer so he could grow up to find a cure for it. His vision is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

Osteosarcoma is the most common bone cancer in children. Typical treatment includes cancer-killing drugs for several weeks followed by surgery. These drugs work for some patients but not for others. Doctors need a way to identify which patients respond to treatment and which don’t. Dr. Roblyer is studying the efficacy of a new light-based technology to determine when and if patients respond to treatment. This technology is low-cost, fast, and measurements are taken with a hand-held or wearable probe, like a Fitbit for cancer. If successful, this research will provide doctors with a new and simple method to personalize and improve treatment for each child with osteosarcoma.

Ewing sarcoma is a cancer of bone and soft tissue in children and young adults, which is fatal if untreated. While often successful, therapies for Ewing sarcoma have severe long-term side effects for survivors. Dr. Lombard is testing a new means of treating Ewing sarcoma, by targeting the mitochondrion, the metabolic hub of the cell. Dr. Lombard and his team have early results to suggest that this new approach may provide a way to efficiently kill Ewing sarcoma cells, with little impact on normal cells and organs. This grant is named for Love Your Melon, an apparel brand dedicated to giving a hat to every child battling cancer in America as well as supporting nonprofit organizations who lead the fight against pediatric cancer.

Progress in improving therapy for Acute myeloid leukemia (AML) has been slow and survival rates for patients remain quite low. Thus, there is a great need for more effective and less toxic therapies for AML. Dr. DeGregori has identified a new molecule called MCJ, the loss of which is associated with the resistance of cancers to therapies. Dr. DeGregori has developed novel drugs that can restore MCJ function in cancer cells, and is investigating whether these MCJ activating drugs can be used improve therapies for AML.

Genes instruct cells to do their jobs through making specific proteins. In the human body, all cells store these "instructions" in the chromosomes. When chromosomes break off, the broken pieces sometimes change places and create new chromosomes. These changes are called chromosomal translocations. Dr. Su is studying how chromosomal translocations cause deadly diseases in children and young adults, and more importantly, is investigating possible clinical options to correct these abnormal conditions.

Childhood brain tumors are frequently quite different than those of adults. Dr. Eck's For the Love of Jack St. Baldrick'’s Research Grant aims to find new “targeted” therapies for low-grade astrocytomas (a type of brain tumor) in children that are caused by a mutation in a protein called BRAF. BRAF mutations are common in cancer, and drugs have been developed that are effective in some tumors caused by one type of BRAF mutation. Unfortunately, these drugs do not work on the BRAF mutation found most often in pediatric brain tumors. Dr. Eck is using detailed information about the molecular structure of the BRAF mutation found in pediatric brain tumors to discover new drugs that specifically target this cause of brain tumors in children. Jack Tweedy was diagnosed with brain and spinal cancer when he was two. Since then he has endured multiple surgeries and 270 weeks of chemotherapy but never fails to uplift those around him. Together with his family, he inspires others to help fund the best research to ensure that all cancer warriors have better treatment options.

The interaction between two important cancer-related proteins called MDM4 and TOP2A may cause cancer and contribute to disease progression. Dr. Zhou is studying the regulation of MDM4 and TOP2A to identify small-molecule inhibitors (agents) that can block the MDM4-TOP2A interaction, leading to inhibition of these two proteins. The results of these studies will provide important clues to help scientists develop novel methods and drugs to specifically and simultaneously target TOP2A and MDM4 for treatment of pediatric cancer patients.

Treatment of childhood acute lymphoblastic leukemia (ALL) using chemoradiation can be successful, but it is difficult to manage treatment-associated side events and secondary cancers. Furthermore, in relapsed/refractory patients, the overall prognosis remains dismal. Direct inhibition of the main proteins promoting cancer (the “oncogenes”) is not successful in ALL. Dr. Ntziachristos's "Just Do It…...and be done with it" St. Baldrick'’s Research Grant will study certain oncogene-supporting mechanisms that might be specific to a diseased state, and not to a healthy state. Dr. Ntziachristos has selected one of these mechanisms to target in ALL models, and is assessing the anti-cancer activity that results. Such experiments could pave the way for clinical trials for high-risk disease. This grant is named for the “"Just Do It...…and be done with it"” Hero Fund created in honor of Sara Martorano who doesn'’t let anything dim her sparkle and has a compassionate heart and smile. It also celebrates the courage of all cancer kids through treatment and the support of their family and friends.

Targeted therapy works by attacking an abnormal gene product that is specific to the cancer type. Only a minority of neuroblastoma types show genetic drivers, which makes it difficult to develop targeted therapy. Most neuroblastomas show too many or too few copies of large chromosomal regions, called CNAs. Dr. Weiss is studying the connection between CNAs and neuroblastoma, to determine if it CNA is a possible candidate for targeted therapy. Dr. Weiss is engineering CNAs to create CNA-driven models of neuroblastoma, which he will then use to identify CNA-specific therapies to treat neuroblastoma.

Dr. Wechsler and his team study how normal white blood cells turn into leukemia cells. They have discovered that a protein called CRM1 is directly involved in turning on specific genes that cause leukemia to develop. Dr. Wechsler is studying this previously unrecognized function of CRM1 by identifying other proteins that are required for CRM1 to turn on. This research aims to allow Dr. Wechsler to design new drugs that can selectively target leukemia cells and increase cure rates.

Neuroblastoma is the second most common solid tumor in children, and is a cancer that frequently metastasizes to the bone marrow. Dr. DeClerck is studying how neuroblastoma cells "teach" bone marrow cells to promote tumor growth.

Drug resistance remains a major obstacle in acute lymphoblastic leukemia (ALL). Instead of targeting only the leukemia cells, Dr. Kim is studying the protective non-leukemia cells that are located in the bone marrow, creating a safe haven for drug-resistant ALL cells. Dr. Kim's team has identified a molecule in leukemia cells that allows leukemia cells to remain in the bone marrow and shelters them from the otherwise toxic effects of chemotherapy. Dr. Kim's Johnny Crisstopher Children’s Charitable Foundation St. Baldrick’s Research Grant is testing a novel inhibitor of this molecule to overcome drug resistance. The mission of the Johnny Crisstopher Children's Charitable Foundation is to raise awareness of pediatric cancer and provide funds for research, treatment, and - ultimately - a cure. Famed illusionist Criss Angel founded the foundation in 2008 for charitable causes but it has now become his life's mission since his son, Johnny Crisstopher was diagnosed with leukemia in 2015 at 20 months old.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, yet currently has no optimal treatment options. Medulloblastoma has been classified into 4 major subgroups, and Dr. Chen is targeting methylation mutations to develop improved therapeutics for two highly-aggressive subgroups of medulloblastoma. To facilitate this, Dr. Chen is establishing precision models of this disease to screen and test for therapeutics. To systematically identify protein targets required for survival of MB cells, Dr. Chen and colleagues are performing a genome screen to look for possible targets, in order to enhance understanding of this disease and lead to novel therapeutic routes.

Medulloblastoma (MB) is a highly aggressive pediatric brain tumor for which safer and more effective therapies are needed. Recent studies have identified four major forms of MB that differ in terms of molecular characteristics and patient outcomes. Dr. Wechsler-Reya is working to identify genes that drive Group 4 MB tumor formation, the most prevalent form of MB, to develop new strategies for treatment of this devastating disease.