Grants Search Results

This institution is a member of a research consortium which is being funded by St. Baldrick's: Consortium for Childhood Cancer Predisposition. For a description of this project, see the consortium grant made to the lead institution: Emory University, Atlanta, GA.

Based on progress to date, Dr. Hoang-Minh was awarded a new grant in 2022 to fund an additional year of this Scholar grant. Brain tumors are the most common cause of cancer-related deaths in children. The current treatments are often associated with lifelong mental and motor deficits, and the tumors often recur. Therapies that specifically and efficiently target the tumors and minimize toxicity to the body are critical to improve clinical outcomes for children affected by these deadly diseases. As the Pray for Dominic St. Baldrick's Scholar, Dr. Hoang-Minh's research is exploring a powerful method that uses the children's own immune system to destroy their brain tumors, known as immune cell therapy. This therapy has emerged as a very effective and safe treatment for blood cancers and several types of solid tumors. It uses powerful immune cells, called T cells, to specifically kill the brain cancer cells and has already shown promising results in preclinical and clinical studies conducted at our institution. This project investigates novel approaches to make this immune therapy even more effective and safer. Dr. Hoang-Minh will also follow the fate of therapeutic T cells using a new, non-invasive imaging technology called magnetic particle imaging. The results of these studies are important as they could improve clinical protocols using immune cell therapies for childhood brain tumors and extend or save the lives of children afflicted with those very aggressive cancers.

This grant is named for the Pray for Dominic Hero Fund. The fund was established in honor of Dominic Liples who lived with joy. He is remembered for compassion and determination while he faced his own difficult battle with a rare and aggressive brain cancer. The Pray for Dominic fund carries on Dominic's legacy of joy and hope by funding research for high-grade gliomas.

Neuroblastoma is a pediatric cancer that originates from mistakes in nerve cell development. Limitations in our mechanistic understanding of disease onset and progression have led to inaccurate patient risk predictions and over-treatment of infants, with long-term side effects. Recently, Dr. Kulesa and colleagues developed a computational model to predict neuroblastoma disease outcome based on a network of six development genes of receptor tyrosine kinase signaling that is more accurate at early disease stages than any current gene list algorithm. What remains to be determined is whether this model can be refined to increase its predictive value and tested to simulate hypothetical treatment strategies with individual patient data. To address these questions, he will include MYCN into the network model, a proto-oncogene gene that is correlated with poor prognosis, and compare model and experiment results of network perturbations that simulate targeted treatments. Dr. Kulesa will take advantage of acquired human neuroblastoma cell lines and our ability to modulate these genes in culture, and patient data from large-scale neuroblastoma genomic databases and published studies. At the conclusion of our study, he will have a better understanding of the mechanistic basis of neuroblastoma disease progression and a refined computational model to more rapidly and accurately predict individual patient disease outcome.

The human immune system is astonishing in its ability to eliminate cells and organisms that give rise to disease. This process of immune surveillance is one of the last lines of defense that protect both adults and children from cancer; however, researchers have found that dysfunctional immune responses can permit cancerous leukemia cells to grow uncontrollably in the body. In this work, Dr. Dreaden will improve upon a drug that attempts to restore immune elimination to leukemia by redirecting a subset of immune cells, so-called T cells, to bind with and kill cancerous cells. By tethering such drugs with molecules that stimulate T cells to multiply, and possibly enable these cells to recognize leukemia cells again at a much later date, he aims to further improve both the strength and durability of responses to this promising class of immuno-therapy. Already, Dr. Dreaden and colleagues have made and screened more than 45 of these unique, multi-functional therapies and aim here to study the precise mechanics by these drugs act on immune cells, as well as their ability to impart memory-like immune responses to leukemia. Given the modular nature of this treatment approach, it could be rapidly extended to a range of other cancer cells, immune cells, and immune stimulating factors in the future.

For the past 15 years, Dr. Northcott has devoted his entire scientific training and early independent career to studying the biological basis of medulloblastoma in large collections of patient tumors. From these efforts, his research has demonstrated that medulloblastoma is not a single disease, but rather a collection of different diseases referred to as subgroups, each of which is associated with distinct genetics, distinct age of onset, and distinct survival patterns. These findings have begun to directly impact how children afflicted with medulloblastoma are diagnosed and treated in the clinic. Currently, his lab consists of a team of basic scientists, computational biologists, and support staff that work collaboratively to understand fundamental questions related to the biological and clinical aspects of the different medulloblastoma subgroups. Leading a scientific program focused on medulloblastoma at St. Jude, Dr. Northcott has the privilege of being part of a collaborative research environment that facilitates working alongside pediatric neuro-oncologist’s leading world class clinical trials, allowing them to combine their expertise to determine why some children survive medulloblastoma and others do not. This group is currently pioneering and implementing innovative technical approaches to study extensive collections of medulloblastoma patient samples at the level of individual genes in single cancer cells. Information gained from these studies enables researchers to accurately model the different medulloblastoma subgroups in the lab and test new therapies before they are evaluated in clinical trials. Overall, his goal is to continue to make transformative discoveries related to the molecular, biological, and clinical characteristics of medulloblastoma subgroups that will improve treatments and outcomes for affected children and their families. The St. Baldrick's Robert J. Arceci Innovation Award is given in honor of the late Dr. Robert Arceci. A pioneer in the field, this award reflects Dr. Arceci's values including creativity, collaboration, and commitment to early- to mid-career scientists.

We know that mental health and physical health are closely connected. For example, teenage cancer patients who receive bone marrow transplants have high rates of anxiety, depression and other mental health issues, which have in turn been associated with relapse and even death rates. Researchers have recently discovered that the immune system may be an important link between the mind and the body -- psychological stress can create a specific pattern of molecular responses in immune cells, which causes inflammation and may produce poor outcomes in cancer. To see if the molecular response pattern indeed associates with altered immune cell function and with mental health symptoms, Dr. Taylor will study blood samples and quality-of-life surveys that are collected from teenage patients undergoing bone marrow transplant. If we can understand the biology of how a teen's mental state affects the cancer in their body, we can develop better ways to improve both psychological and medical outcomes in these vulnerable patients.

Rhabdomyosarcoma is a common cancer in kids. It can be a very aggressive disease, especially a type that is caused by a genetic change that creates an abnormal cancer-driving protein in the cell, called "P3F". P3F-driven rhabdomyosarcoma shows a strong tendency to spread to other parts of the body, which is what typically leads to death from the disease. P3F is a very hard drug target. However, P3F works together with other machinery in the cell to cause rhabdomyosarcoma. Such machinery could be targeted to interfere with P3F effects, but is not well understood. Dr. Jedlicka and colleagues have recently found new parts of this machinery that help P3F cause rhabdomyosarcoma to spread to other parts of the body. In this project he will better understand how this new machinery works and how it could be targeted to interfere with rhabdomyosarcoma spread. This work could identify new ways to inhibit the aggressive nature of this disease and improve patient outcomes.

This grant is generously supported by Marlee’s Smile, a St. Baldrick's partner, founded in honor of 12-year-old, Marlee Pack. Diagnosed with alveolar rhabdomyosarcoma; she relapsed three times in four years. After the final relapse, Marlee had to make a decision no child should have to: continue painful, toxic treatments or enter hospice care. She passed away on February 23, 2019. Our mission at Marlee’s Smile is to change the lives of kids with cancer, one smile at a time in two ways. We give a custom Build-A-Bear to every child fighting cancer, as well as their siblings to honor Marlee’s giving heart as she knew the comfort of a furry friend. We fund targeted research of pediatric cancers, specifically sarcomas to honor Marlee’s dying wish that no child should have to suffer the pain and hopelessness of current cancer treatments.

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.

This grant is generously supported by the TeamConnor Childhood Cancer Foundation. TeamConnor Childhood Cancer Foundation's mission is to raise funds for national childhood cancer research programs, to build awareness that only a fraction of the NIH’s annual funding supports childhood cancer research, and to support inpatient programs. Founded in 2008 in honor and memory of Connor Cruse, TeamConnor has funded over $4M in pediatric cancer research grants across the United States.

The proto-oncogene MYCN is amplified in approximately half of patients with high-risk neuroblastoma. At relapse, tumors from high-risk patients typically activate a pathway called "MAP kinase signaling" through genetic mutations including loss of NF1, which normally dampens MAP kinase function. Since relapsed neuroblastoma is generally therapy resistant, these data suggest that MAP-kinase activation contributes to therapy resistance. Does MAP kinase signaling contribute to therapy resistance in MYCN-amplified neuroblastoma at diagnosis? Dr. Weiss proposes that dependence on increased MAP kinase signaling in MYCN-amplified neuroblastoma enables rare cells within this heterogeneous tumor to evade chemotherapy. This therapy-resistant population then undergoes selection for further activation of MAP-kinase signaling, reinforcing therapy resistance. How does MYCN drive MAP kinase? The NF1 tumor suppressor blocks MAP kinase signaling. Mis-splicing of the NF1 messenger RNA in neuroblastoma cells results in NF1-23a, a protein with decreased ability to block RAS. Inclusion of NF1 exon 23a is regulated by the RNA splicing proteins "T-cell intracellular antigen 1" (TIA1) and "TIA1 Like gene" TIAL1, both of which are MYCN target genes. If activation of TIAL and TIAL1 (TIA/L1) in MYCN-amplified neuroblastoma activates MAP-kinase signaling in primary tumors at diagnosis, does traditional treatment of these tumors select for further flux through MAP-kinase signaling, to enhance resistance at relapse? This is the issue that Dr. Weiss' proposal addresses. Successful completion clarifies the importance of MYCN-TIA/L1 axis as a driver of resistance in neuroblastoma, and suggests a a translational path to improve outcomes in neuroblastoma.

Dr. Weiss' grant is generously supported by the Arden Quinn Bucher Memorial Fund, a St. Baldrick's Hero Fund. Arden’s intelligence, empathy, and dynamic personality charmed everyone and is now her legacy. Before her neuroblastoma diagnosis on October 11, 2007 at age two, she happily played with boundless energy and imagination. Even throughout her difficult months of treatment, Arden bravely managed to keep smiling and learning. This fund supports St. Baldrick’s mission: funding the most promising research, wherever it takes place to provide kids fighting cancers less toxic, more effective treatments allowing them to live longer, healthier lives.

Based on progress to date, Dr. Conneely was awarded a new grant in 2022 to fund an additional year of this Fellow award. 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 is generously supported by Double Deckers Destroy AML, a St. Baldrick's Hero Fund. Joel and Seth were not only identical twins but best friends. In an ironic twist of fate, both boys were diagnosed with Acute Myeloid Leukemia just three months apart. With the overlapping diagnoses and treatments, the family was separated for months at a time and looked forward to days when they could be together at home. Joel and Seth both received bone marrow transplants and endured complications from the procedures. Sadly, both boys relapsed. Surrounded by their loving family, Joel died in November 2017 at the age of three, followed by Seth in May, 2019 when he was four years old. The twins were named as 2020 Ambassadors for St. Baldrick's so their story can continue to inspire many. The Double Deckers Destroy AML Hero Fund was established because the Decker family strongly believes more research is needed for AML, especially when the disease has relapsed. They want to support research so other families won’t have to say goodbye too soon.

Although rates of cure for childhood cancer have greatly improved in recent years, thousands of children continue to suffer from advanced, incurable cancer. Healthcare professionals bear a responsibility to ensure that the care of children with advanced cancer meets the goals and wishes of patients and their families. However, we do not know whether we fulfill this aim in pediatric cancer care. Dr. Ananth's prior research reveals intensive healthcare use near the end of life for children with advanced, incurable cancer. This includes lengthy stays in the intensive care unit and common use of interventions like breathing tubes. Yet, healthcare professionals worry that intense care toward the end of life for children with cancer may increase child and family suffering. In adults with cancer, quality measures have been developed to evaluate where care is most intense, or poor quality. This has consequently allowed researchers to develop interventions to improve the quality of care for adults with incurable cancer. Unfortunately, there are no comparable measures or standards for what constitutes good, or high quality, end-of-life care for children with cancer. Dr. Ananth seeks to address this problem. The overall objectives of this research are to (1) refine a list of potential measures of high quality end of life for children with cancer, and (2) develop an innovative questionnaire to systematically evaluate whether patients are receiving high quality end-of-life care. She hopes that, through this work that is distinctly family-centered, she can develop interventions to enable healthcare teams to provide optimal, compassionate care for children who have incurable cancer.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Consortium for Childhood Cancer Predisposition. For a description of this project, see the consortium grant made to the lead institution: Emory University, Atlanta, GA.

Pediatric cancers are often comprised of mixtures of cells with different characteristics. Some of the most important differences relate to chromosomal changes, with some cells having a normal or nearly normal chromosome profile, others having altered numbers of intact chromosomes, and yet others having extra or missing copies of one or more chromosome segments. Prior studies have shown that cancers with more segmental changes are usually more aggressive and therapy-resistant, but the specific effects associated with the different chromosomal changes are unknown. Here Dr. Cobrinik and colleagues will define the effects of such changes in two pediatric cancers -- retinoblastoma and neuroblastoma -- by isolating individual cells within the tumors that either have or lack specific chromosome changes, comparing their overall gene expression and cell signaling profiles, and identifying the critical changes that increase malignancy. The study involves three investigators with expertise in neuroblastoma, retinoblastoma, and a novel single cell sequencing approach that enables us to distinguish and characterize the chromosomally distinct cells within individual tumors in unmatched detail. This study is expected to reveal the most central features that distinguish more versus less aggressive cancers, as a critical step towards targeting and subduing the more aggressive and lethal cells within individual tumors.

Pain is one of the most common and distressing symptoms that children with cancer face. Pain can persist between clinic visits but may not be reported unless the child is specifically asked. Dr. Linder's team co-designed a game-based symptom reporting app, Color Me Healthy, with elementary school-age children with cancer. In the initial test of the app among children receiving chemotherapy, more than half of children's symptom reports included a report of pain. Parents reported that the app helped them better understand their child's symptoms. Children and parents also gave important feedback to improve the app. During the first phase of the study, Dr. Linder will use feedback from children and parents to make important changes to the app to enhance how children report pain using the app and how children's data can be understood by parents and clinicians. In the second phase of the study, she will ask children to use the newly enhanced pain assessment feature and ask how parents and clinicians used children's data to help relieve their pain. Completing this study will allow Dr. Linder to use the app in a larger study to improve pain management and quality of life among children receiving cancer treatment.

Pediatric high-grade gliomas (pHGGs) are a fatal childhood cancer of the brain. Deregulation of specific histone modifications, both with and without a direct link to specific mutations, have been identified in these tumors. This project will investigate histone H3 post-translational modifications (PTMs) in pHGGs to advance our understanding of tumor development and understanding of biologic characteristics, and to promote the identification of effective therapies for improving the outcomes for patients with these tumors.

This grant is generously supported by The Benicio Martinez Fund for Pediatric Cancer Research, a St. Baldrick's Hero Fund created in honor of Benny's fight with cancer and supports cures and better treatments for kids like him. Weeks after being the top fundraiser in his 6th grade class and shaving his head at his school’s event, Benny was diagnosed with medulloblastoma. Since then he has had brain surgery, radiation and chemotherapy. Despite complications from treatment and setbacks, Benny has an amazing can-do attitude and is battling the cancer with courageous determination.

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.

This grant is generously supported by the Rally for Ryan Fund, a St. Baldrick's Hero Fund. Ryan was diagnosed with ALL when he was 7 years old and began treatment immediately. Initially labeled “high risk” due to a poor response, he completed 3½ years of a difficult treatment protocol before relapsing 11 months later. After his third relapse and an unsuccessful immunotherapy trial, Ryan had a bone marrow transplant in December 2020. He is currently fighting graft vs. host disease but is doing well and is optimistic for a good response. The Campanaros created this Hero Fund to celebrate Ryan’s courageous spirit and knowing firsthand the importance of research, to raise funds to find better treatments for kids with cancer.

Acute myeloid leukemia (AML) is an aggressive pediatric cancer associated with poor outcomes. Current therapies are toxic and result in a high incidence of late effects; including infertility, heart failure, and second cancers. Therefore, distinguishing who will be cured with chemotherapy alone from those who require more intensive therapies is critical to improving cure rates in AML while limiting treatment related late effects. The presence of small numbers of persisting leukemia cells after chemotherapy has become an important predictor of leukemia relapse. However, current assays used to detect residual leukemia have limited sensitivity and many patients with "no detectable leukemia" still go on to relapse. This underscores the need to identify and develop more accurate and sensitive leukemia detection assays for AML. This project aims to develop a novel assay that harnesses "best in class" technologies to enable detection of one leukemia cell for every one million normal cells -- a sensitivity that eclipses the current standard of care by more than one hundred-fold. Additionally, unlike many other novel methods for detecting leukemia, this assay will be universally applicable to every patient diagnosed with AML. Finally, this assay will reveal not simply whether or not leukemia cells are present, but the exact genetic code comprising the remaining leukemia cells. Successful validation of Dr. Huang's assay will therefore fill a critical unmet need in the field of AML, and the resulting product will be an optimized test ready for clinical use.

A portion of this grant is generously supported by RowOn 4 A Cure, a St. Baldrick's Hero Fund. Rowan was a happy, spunky, funny, smart, and smiley little girl. With that same tenacity, she faced her cancer diagnosis of a rare form of acute myeloid leukemia when she was three. Despite intense chemotherapy and radiation and a successful cord blood transfusion, Rowan relapsed after a brief remission. The family relocated in search of another treatment option but before one could be found, Rowan sadly passed away. RowOn 4 A Cure was established to honor Rowan and continue her fight against AML by raising awareness and funds for research to find better options for treatment of relapsed AML and ultimately, a cure for the disease. Her family remembers Rowan’s perseverance during tough treatment days and intend to make an impact as they “Row On” to find a cure.

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.

Based on progress to date, Dr. Bertrand was awarded a new grant in 2022, 2023, and 2024 to fund an additional year of this Scholar grant. Ependymoma is an aggressive pediatric brain tumor that is treated with surgery and radiation, but is resistant to chemotherapy. Ependymoma can be divided into different groups by location and biology. One type of ependymoma is driven by a fusion cancer-causing protein RELA-fusion. There are currently zero available drug therapies that target this protein, and we have a poor understanding of its function in cancer. Dr. Bertrand's research seeks to understand how this protein induces cancer in cells and models so that we can devise new treatments.

The 2024 portion of this grant is funded by and named for Hannah’s Heroes, a St. Baldrick's Hero Fund established to honor Hannah Meeson. At age six she was diagnosed with anaplastic medulloblastoma. After a relapse and several additional months of treatment, Hannah currently shows no evidence of disease. Throughout her treatments, Hannah never complained and remained positive and happy. This fund pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

Awarded at Baylor College of Medicine and transferred to St. Jude Children's Research Hospital.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Consortium for Childhood Cancer Predisposition. For a description of this project, see the consortium grant made to the lead institution: Emory University, Atlanta, GA.