Grants Search Results

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.

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 is formed by mutations that activate the Hedgehog signaling pathway. Dr. Vokes is investigating how the Hedgehog pathway controls the expression of genes through specific control regions of DNA. Dr. Vokes and his team are studying those DNA control regions in medulloblastoma cells, to determine if they can control the expression of target genes, thereby providing a possible therapeutic target for medulloblastoma.

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.

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.

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.

Genetic studies have identified the molecular causes of childhood cancers such as T-cell leukemia and neuroblastoma. A recurrent theme in these cancers is abnormal activation of the MYC gene. Accordingly, researchers like Dr. Wendel have spent much time and effort in trying to identify inhibitors of MYC as they believe these could be very powerful therapies for these childhood cancers. Dr. Wendel and his colleagues recently found a new way to block the production of MYC using a natural compound. The natural product is rare and hard to come by and therefore Dr. Wendel and his colleagues are exploring ways to generate synthetic drugs based on this plant product. With support from the St. Baldrick’s Foundation they are working to bring this new strategy to the clinic. They focus especially on heavily pre-treated and relapsed childhood leukemia because affected children have few options and they hope to make a difference.

Neuroblastoma is a cancer of the cells that become nerve tissues in the body, except in the brain. Dr. Bernstein is studying the effect of a particular mutation in neuroblastoma – an event that alters the DNA sequence to promote cancer. This mutation lies in a gene called ATRX. Dr. Bernstein takes a genomics approach to understand how ATRX mutations promote neuroblastoma in order to discover new therapies for children with ATRX mutations.

The chemotherapy drugs used to treat cancer do not always work, because only a small amount of the drug ever gets to the tumor. Also, these drugs are very toxic to the patient. However, if we package the drugs into little packets called nanoparticles, we get a lot more drug into the tumor because their blood vessels are leaky. Also, the nanoparticles are too big to get into most normal tissues. Dr. Brodeur's Invictus Fund St. Baldrick’s Research Grant aims to find successful ways to give less total drug, have a much greater effect on the tumor, and have much less toxicity to the patient. This grant is funded by and named for the Invictus Fund, a St. Baldrick's Hero Fund created in memory of Holden Gilkinson and honors his unconquerable spirit in his battle with bilateral Wilms tumor by funding cures and treatments to mitigate side and late effects of childhood cancer.

Leukemia is a form of blood cancer, and is the most common cancer in children. Overall, cure rates for children with some forms of leukemia is very high (almost 90%). However, when leukemia occurs in babies, the cure rate is only 40%. Dr. Brown has discovered that these leukemias may be harder to cure because the cancer cells have abnormal ways of organizing their DNA. Dr. Brown's research aims to understand this better to develop new treatments that will reverse this abnormal DNA organization and make the leukemias easier to cure.

Graft-versus-host Disease (GvHD) is a common devastating side-effect of bone marrow transplantation. More than 50% of children suffer from moderate to life-threatening GvHD after bone marrow transplantation. GvHD results when the primary leukemia-fighting cells in the transplants become overzealous and begin to attack not only the leukemia, but also the patient’s skin, intestines, liver, and mucosa. Dr. Choi has demonstrated that modulating a gene called interferon gamma receptor in these cells preserves the potent anti-leukemia activities while inhibiting GvHD. Dr. Choi's Rays of Hope St. Baldrick’s Research Grant aims to identify the mechanism underlying the actions of this gene to develop safe and efficient therapeutic strategies. This grant is named for the Rays of Hope Hero Fund which honors the memory of Rayanna Marrero by giving hope through research funding. She is remembered for her infectious smile and energetic spirit which continue to inspire so many.

Retinoblastoma is a cancer of the eye in children that can cause blindness or death. New therapies are needed to combine with existing drugs to save vision, eyes, and lives. Dr. Corson has developed a new chemical that blocks abnormal blood vessel growth in the eye without side effects. By blocking new blood vessel formation, we could starve a growing retinoblastoma tumor of oxygen and nutrients and stop its growth. To determine this, Dr. Corson's research aims to test this new chemical in a model of retinoblastoma, both alone and in combination with an existing drug.

Medulloblastoma is the most common malignant brain cancer in children. Dr. Erdeich-Epstein's research aims to improve medulloblastoma treatment based on its biology. Dr. Erdeich-Epstein and colleagues have identified PID1 as a candidate tumor suppressor after finding that higher PID1 killed medulloblastoma cells and slowed medulloblastoma growth in models. This research is to examine PID1 further to help develop drugs to improve response of medulloblastoma to treatment.

Over the last decades the introduction of multi-agent chemotherapy protocols have resulted in major advances in the treatment of pediatric acute lymphoblastic leukemia (ALL). However the prognosis of patients whose leukemia relapses after an initial transient response to therapy remains highly unsatisfactory with cure rates of less than 40% despite intensive treatment. Dr. Ferrando's research aims to address fundamental questions on the role and mechanisms of genetic mutations associated with chemotherapy resistance to pave the way for the development of improved therapies for the treatment of relapsed ALL patients.

Dr. French's research focuses on a deadly cancer of children and young adults called NUT midline carcinoma. A while back Dr. French discovered the cancer protein that causes this disease, called BRD4-NUT. This discovery led to the development of inhibitors to BRD4 that are now being used to treat NUT midline carcinoma and this has expanded to the treatment of more common cancers in clinical trials. However, NUT midline carcinoma remains incurable. Recently, Dr. French discovered an additional and completely new protein that associates with BRD4-NUT, called a ZNF532, that helps BRD4-NUT cause this cancer. This research aims to understand how this new cancer protein contributes to the malignancy in this disease.

Alveolar rhabdomyosarcoma (aRMS) is a cancer of the soft tissues. This disease often responds to chemotherapy, but in many patients available treatments fail. Dr. Keller's lab identified how a cancer-causing gene called Pax3:Foxo1 leads to treatment failure. Remarkably, Pax3:Foxo1 can be silenced by entinostat, a drug recently granted FDA breakthrough designation for breast cancer. Dr. Keller has found that entinostat dramatically improves sensitivity to chemotherapy, but efficacy in relapsed disease is unknown. This research aims to identify whether entinostat makes relapsed aRMS sensitive to chemotherapy, paving the way for an evidence-based clinical trial that could save lives.

Rhabdomyosarcoma (RMS) is a devastating childhood cancer of muscle. Using models, Dr. Langenau recently identified NOTCH as a critical driver of RMS growth. This research aims to examine NOTCH inhitors for anti-tumor effects in RMS, providing rationale for moving these drugs into phase I clinical trials.

T-lymphoblastic leukemia is a blood cancer with a higher rate of chemo-resistance and central nervous system involvement than B cell leukemia. Dr. Letterio's research utilizes models and molecular biology techniques to test how a novel molecular target controls the development of acute T-lymphoblastic leukemia in the bone marrow and the central nervous system. Success in this new area of research will offer new hope in the development of novel therapies against T-cell leukemia.

The causes of relapse of acute lymphocytic leukemia (ALL) remain unknown and there are limited therapies for such children. Dr. Licht characterized a mutation of a gene present in 10-20% of children with relapsed ALL. A mutation in this gene that may cause relapse by reprograming cells to grow more rapidly and become chemotherapy-resistant. Using a new technique Dr. Licht's Do It for Dominic St. Baldrick’s Research Grant aims to determine how the mutation increases growth and causes drug resistance in order to devise new therapies for relapsed ALL. The grant is named for the Do It for Dominic Hero Fund created in memory of Dominic Cairo. His family and friends continue to raise funds and support St. Baldrick’s to find cures for childhood cancers so no child ever has to go through what Dominic had to endure.

Rhabdomyosarcoma is an aggressive childhood cancer that often arises in muscle. Because of the poor survival, researchers are searching for genes underlying this cancer, with the hope of blocking them. A research scientist who studies how normal muscle forms found that a gene called MEST helps in defining muscle cell precursor identity. Dr. Linardic's lab had noticed that in rhabdomyosarcoma, MEST was highly expressed, suggesting that maybe MEST tricks cells into constantly growing. This project focuses on learning how MEST contributes to rhabdomyosarcoma, and how to block it.