Grants Search Results

Based on progress to date, Dr. Dallas was awarded a new grant in 2013 to fund an additional year of this Scholar award. Hematopoietic cell transplantation is a potential cure for various pediatric cancers. Approximately one-third of patients who require a transplant do not have a suitable matched donor, and umbilical cord blood transplants are an increasingly utilized alternative, with over 20,000 performed since 1988. One of the major complications is the increased risk for serious infection due to the prolonged period of time the patient's immune system is suppressed after transplantation. Dr. Dallas and her team have developed a novel method to generate cells that will hasten the time to recovery. Their goal is to translate these findings to pediatric patients and improve their survival.

Based on progress to date, Dr. De Oliveira was awarded a new grant in 2014 to fund an additional year of this Scholar award. New therapeutic approaches are needed for pediatric leukemia and lymphoma, because patients with refractory or relapsed disease still have a survival rate of less than 50% with current therapies. This research involves a novel cancer immunotherapy protocol, transferring a gene into the patient's own blood stem cells, giving rise to immune cells able to directly and specifically target a surface molecule that is present in more than 95% of leukemias and lymphomas. This project evaluates the cancer cell destruction by the modified immune cells, setting a basis for future clinical trials.

Based on progress to date, Dr. Diede was awarded a new grant in 2013 to fund an additional two years of this Scholar award. DNA methylation is a normal process used by cells to allow information to be passed on to successive generations of cells. Cancer cells can exploit this to silence genes that help prevent tumor formation. This has been extensively studied in adult cancers, but not in pediatrics. Given the relatively short time frame in which pediatric cancers develop, aberrant DNA methylation may play a very important role. This research is to better understand how it promotes the formation of pediatric rhabdomyosarcoma, and may open an exciting new area for treatment and provide valuable biomarkers for cancer detection, diagnosis, and risk assessment.

Based on progress to date, Dr. Gamper was awarded a new grant in 2014 to fund an additional year of this Scholar award with generous support from the McKenna Claire Foundation. Chemotherapy and radiation destroy both cancer cells and normal cells, with toxic effects on growing children during treatment and afterwards. Immunotherapy has the potential to destroy only cancer cells, but it has not lived up to its full potential because cancer cells can promote inappropriate immune responses or simply turn immune cells off. This research examines the function of T cells that lack the ability to methylate DNA; such cells may be better at killing tumors. This may help more patients with high-risk pediatric tumors, and decrease the risk of late-effects by reducing the need for more chemotherapy and radiation.

Based on progress to date, Dr. Rabin was awarded a new grant in 2014 to fund an additional year of this Scholar award. Children with Down Syndrome have a 20-fold increased risk of developing acute lymphoblastic leukemia (ALL), and suffer significantly more frequent and severe complications associated with chemotherapy, including life-threatening infections. This research involves abnormal activity of genes called JAK2 and CRLF2 and new drugs. It will also investigate whether gene variants that are associated with severe infection in the general population occur more frequently in those with Down Syndrome and ALL who suffer severe infectious complications. If so, patients identified as high-risk for infection could be identified ahead of time, to receive enhanced supportive care to prevent severe toxicity.

This grant is made with generous support from the “Daniel the Brave Fund" created in memory of Daniel Gomez to honor his bravery and provide hope for those still in the fight.

Based on progress to date, Dr. Singh was awarded a new grant in 2013 to fund an additional two years of this Scholar award. Diamond Blackfan anemia (DBA) is an inherited condition that leads to anemia, birth defects and cancer. Over-expression of the p53 protein, which protects against tumor formation, may actually lead to DBA. One of p53's functions is to cause cell death in damaged or stressed cells. Chronic over-expression of p53 may lead to an environment that leads to cancer transformation and survival. Understanding the conditions that promote the formation and survival of cancer cells is vital to improve early diagnosis and treatment of childhood cancer.

Leukemia is cancer of white blood cells and accounts for about 25% of all childhood cancers. Human chromosomes are normally subjected to various environmental and developmental challenges that might cause breaks, called translocations. While almost all of those breaks are efficiently repaired by the DNA repair machinery, translocations do arise from very rare events when mistakes occur during the repair, increasing the risk for leukemia in children. This study involves basic questions about the cause and process of translocation to better understand the underlying causes of leukemia, potentially leading to the discovery of targets for new therapeutic strategies.

Most cancer therapies have significant toxicity, thus new treatment strategies are needed. Pediatric patients with cancer are excellent candidates for immunotherapy because their immune system is more robust compared to adults. Due to our lack of understanding of how to best activate these specialized anti-cancer cells, progress in pediatric immunotherapy has lagged behind. This research focuses on how we can best activate specific T cells to defend the immune system against tumors, specifically gliomas (brain tumors) and advances the field of immunotherapy as a promising form of treatment for these children.

Rhabdomyosarcoma is the most common cancer that originates in the soft tissue of the body in children. There are two subtypes, embryonal (ERMS) and alveolar (ARMS), and children with ARMS have poorer response to conventional chemotherapy and radiation therapy, and much lower survival rates than those with ERMS. This research aims to discover chemical inhibitors of a gene called PAX3-FKHR and how "knocking down" that gene may help patients respond better to chemotherapy.The goal of this project is to establish a new approach for developing drugs to effectively treat ARMS.

The human body has an ability to detect and eliminate cancer through the immune system, but cancer cells can escape detection. Dr. Curran's research attempts to overcome this tumor escape via gene therapy mediated treatments. Pediatric leukemia is the most common childhood cancer, and patients with recurrent or resistant leukemia have limited options for treatment. Redirecting the immune system to eradicate resistant leukemia cells will provide a new possibility for a cure. Also, by specifically targeting cancer cells, we eliminate the long term complications associated with the conventional treatments of surgery, chemotherapy, and radiation. Dr. Curran was a St. Baldrick's Fellow and now has a faculty position.

Current therapies for neuroblastoma include the use of powerful chemotherapy, which weakens the immune system and can lead to life- threatening infections. As a result, these immune-compromised patients frequently require medication such as granulocyte colony-stimulating factor (GCSF), which helps the body produce white blood cells to help fight infection. In many adult cancers, GCSF has been found to increase the growth of cancer cells in a laboratory setting. Dr. Kim is studying how GCSF and GCSF-R enhance tumor growth, to clarify the appropriate use of GCSF in patients and determine whether GCSF- receptor may be a new therapeutic target in neuroblastoma.

Neuroblastoma is a solid tumor cancer of very young children, originating in the nerve tissue of the neck, chest, abdomen, or pelvis, but most commonly in the adrenal gland. About 45% of children diagnosed have advanced "high risk" disease, for which the survival rate is less than 40%. This project tests the new hypothesis that specific ceramide types and/or expression of sphingolipid enzymes control the growth and invasion of neuroblastoma. The role of a particular family of enzymes called ceramide synthases will also be examined. The goal is to develop new therapeutic strategies for the treatment of neuroblastoma.

Hodgkin lymphoma is a cancer of the immune system and is the most common cancer for children ages 15-19. It arises from Reed-Sternberg (RS) cells, which have two or more nuclei and often have gained or lost chromosomes. This research explores the workings of a protein called KLHDC8B, which is expressed during cell division and is altered in cases of familial Hodgkin lymphoma. Dr. Krem also uses blood and tissue samples from patients to find changes in proteins that are related to KLHDC9B. Those other proteins may be important for preventing onset of Hodgkin lymphoma.

Precursor B-lymphoblastic leukemia is a type of blood cancer in which too many immature white blood cells are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia (ALL). This project studies how specific B-precursor ALL cells are wired and how to disrupt this wiring by treating patients with specific and novel medications. The research improves our understanding of the biochemical mechanisms critical for the development of targeted therapies.

In 2009, the St. Baldrick's Foundation awarded a grant to the Pediatric Blood and Marrow Transplant Consortium (PBMTC) to construct a clinical trials infrastructure that would allow high-quality, appropriately monitored, multi-center pediatric trials. This grant,awarded in 2010, moves that project further towards its goals of: 1) increasing safety for pediatric patients after transplant by using a new medicine that has been shown in adults to treat leukemia with lower toxicity, 2) reducing relapse by giving immune therapy before and after transplant to leukemia patients, and 3) exploring the feasibility of new cellular therapy approaches aimed at preventing relapse.

Rhabdomyosarcoma, the most common soft tissue cancer in children, has two main forms; each behaves differently, so recognition is important for proper treatment. This research builds on previous studies that identified unique genes associated with one form. The proteins from these genes can be used to create special stains that are both affordable and accessible to hospitals that don't perform gene studies. This enhances our understanding of the biology of rhabdomyosarcoma, allow rapid identification of high risk patients who may benefit from specific therapies, and prevent overtreatment of patients with low risk tumors.

Pediatric patients who have bone marrow transplants have an impaired immune system, and the resulting infections can cause bacterial, viral and fungal infections and even death. Unfortunately, medicines to treat these infections are not adequate in many cases; an intact immune system is needed to achieve appropriate responses to infectious agents. The goal of this research is to expedite the immune recovery after transplant. This would result in better responses to infections and improvement in the lives and survival of patients. Dr. Stefanski was a St. Baldrick's Fellow and now has a faculty position.

A type of brain tumor called diffuse intrinsic pontine glioma (DIPG) has no known cure. Radiation therapy offers some temporary relief, but nearly all children die from this cancer within 1 year. A promising form of drug delivery, convection-enhanced delivery (CED), offers many benefits including allowing high concentration of drugs to reach the brain tumor. This study focuses on drug distribution following this new form of drug delivery. By relating drug distribution and radiation dose to tumor response, a better treatment can be designed. Resulting clinical trials for a new therapy may eventually cure DIPG.

Ewing sarcoma (ES) is one of the most common sarcomas in children, caused by a genetic abnormality called a "chromosomal translocation." This study has two goals. First, to understand the normal function of the protein EWS, to learn about what goes wrong in Ewings tumors. Second, to understand what other genetic events are required to turn normal human cells into Ewing sarcomas. Our approach is to try to combine EWS/FLI-1 expression with other genetic events in the type of human cell that we know gives rise to ES.

This grant is to the New Approaches to Neuroblastoma Therapy (NANT) consortium, to develop and test new therapies with high potential for improving survival. NANT links laboratory and clinical investigators to develop therapies that are tested at 15 North American neuroblastoma centers, supported by the NANT Operations Center at Children's Hospital Los Angeles. The strategy includes accurately evaluating response with "biomarkers" for tumor cells in blood and bone marrow combined with sophisticated imaging of tumors, essential for "personalized treatment" to predict if the treatment will benefit the patient. NANT studies enable definitive testing later in larger patient numbers. Funds Administered by the Children's Hospital Los Angeles.