Grants Search Results

Recently the Meshinchi lab discovered that mesothelin, a cancer-specific antigen, is highly expressed in a subset of childhood AML cases, a result that both highlights the distinct genetic differences between adult and pediatric cancers and opens the door for the development of more targeted therapies. Dr. Kolb is developing novel combinations of bispecific T-cell engaging antibodies, called SMITEs (Simultaneous Multiple Interaction T-cell Engagers) that will co-target mesothelin and the AML marker CD33. These T-cell engaging protein pairs physically link cancer cells to cytotoxic T-cells resulting in more potent and selective killing than single agents alone.

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!

Brain tumors are the most common solid tumor in children, and diagnostic imaging guides almost every step in the care of children with brain tumors. However, currently available imaging methods have limited accuracy. Dr. McConathy is using an amino acid tagged with radioactivity (FET) to detect abnormal metabolism in tumor tissue using positron emission tomography (PET) in combination with magnetic resonance imaging (MRI). He expects this new imaging technique to improve the ability to see brain tumors before and after surgery to help doctors better plan the treatment of children with brain tumors. In the long term, Dr. McConathy expects FET-PET/MRI to help select and plan the best therapies and increase the chance of achieving cures.

Glucocorticoids, which are sometimes called "steroids", are a type of drug used to treat all children, adolescents, and adults with acute lymphoblastic leukemia (ALL). In fact, there is substantial evidence that glucocorticoids are the single most effective drugs used to treat ALL, and that relapse is frequently due to the fact that they stop working. Although glucocorticoids have been used for over 50 years, we still do not fully understand how they kill ALL cells and why some ALL cells become resistant and cause relapse. Dr. Shannon has developed a novel approach for generating, transplanting, and treating ALL in models that now provides an unprecedented opportunity to uncover mechanisms of drug response and resistance. The purpose of this research project is to study ALL cells that have become resistant to glucocorticoids during treatment in order to identify the underlying reasons and to use this knowledge to develop better ways of treating them.

Neuroblastoma is one of the most common childhood cancers. There are different subtypes of Neuroblastoma; some have a very poor prognosis for the patient. Dr. Stockwell's team has identified a new aggressive subtype of Neuroblastoma, called "mesenchymal", and sought new therapies that can specifically target this subtype. Since genetic markers that can identify patients with the mesenchymal subtype are know, a selective therapy will have a greater chance of success in the clinic. They recently discovered that a common type of cholesterol-lowering drug, called statins, are potent and selective killers of mesenchymal neuroblastoma cells in the lab. There are many different statins, and now Dr. Stockwell is determining which is the most potent drug and exploring why the mesenchymal subtype is so sensitive to statins. He is also testing these drugs in models of the disease to show that statins are effective at killing mesenchymal neuroblastoma cells. Since these drugs have a documented safety profile in children and well-studied pharmacological activity, these drugs can be brought through preclinical testing relatively quickly and developed as novel therapies for this aggressive pediatric cancer.

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.

Children diagnosed with brain tumors and their parents have many challenges when there is little hope for a cure. Research shows that children who have an incurable brain tumor and their parents are stressed, less happy with their lives, and in poorer health when compared to healthy children and their parents, yet no known helpful coping strategies have been developed for this brain tumor population. Mindfulness exercises are a type of coping tool that help people pay attention to the present moment and handle difficult emotions that come up when facing very stressful life events. In particular, mindfulness exercises have been shown to improve quality of life in children and adults with terminal illness.

With the MaxLove Project Fund St. Baldrick's Supportive Care Research Grant, Dr. Allen is evaluating a new coping program using age-appropriate mindfulness activities to improve the quality of life of children diagnosed with an incurable brain tumor and their families. Coping interventions are greatly needed for this population. The MaxLove Project Fund honors the survivorship journey of Max Wilford who was diagnosed with a brain stem tumor at the age of four. Despite several surgeries and an intense treatment protocol, Max is now able to be a “regular” kid due in large part to integrative therapies he received.

Dr. Deatrick is developing family support and education materials for maternal caregivers of young adult survivors of childhood brain tumors to improve their quality of life and quality of life of the survivors. Training in Problem Solving (TIPS) for Caregivers, leverages past research, eHealth, and Bright IDEAS family problem-solving intervention (an evidence-based intervention for caregivers of children newly diagnosed with cancer) to target challenges identified by maternal caregivers to their family management. TIPS is targeted to caregivers with “condition-focused FM” (family life organized around the special needs of the survivor). Using the prototype session developed in partnership with maternal caregivers, Dr. Deatrick will work with them to design the web-based intervention. She will develop other sessions of TIPS and adapt them to technology, which will be used “live” online with a health care provider and online with interactive homework sheets, videos, and other resources. Future research will involve fathers and other caregivers, survivors, and other family members.

Children and adolescents with cancer and their families are at increased risk for psychosocial problems that can contribute to poorer health and quality of life, and it has been recommended that pediatric cancer centers develop programs to screen patients and families for psychosocial risk. The majority of pediatric cancers centers do not have practices in place to effectively and routinely screen all patients and families for psychosocial difficulties, with time and resources being acknowledged as barriers to implementation. Dr. Gilleland Marchak is developing a novel, patient-friendly technology to screen for psychosocial risk and evaluating its use at a large pediatric cancer center. Study outcomes will include data related to feasibility and acceptability of electronic screening, as well as efficacy in identifying families in distress and connecting them with family support team members to address problems in real time. By successfully leveraging technology to reduce barriers to universal psychosocial screening, we can improve communication between oncology providers and families regarding critical mental health, neurocognitive, and social issues that may negatively impact pediatric cancer treatment and health outcomes.

Cancer-related pain greatly compromises quality of life, and can increase disease morbidity, mortality, and healthcare costs by reducing children's compliance to medical procedures. The burden of cancer-related pain does not end when treatment concludes: many survivors of childhood cancer report cancer-related pain well into adulthood. Thus, there is a critical need for interventions that can reduce pain during and after children's treatments for cancer. Dr. Marusak is testing whether a martial arts therapy that centers around mindful breathing and meditative techniques can reduce pain and the underlying brain mechanisms in young cancer patients and survivors.

The survival rates of pediatric cancers have dramatically improved over the past 40 years due to aggressive treatment regimens, which have side effects. Anthracyclines are one class of chemotherapy drugs that have been used to treat more than 190,000 childhood cancer survivors but cause risk of cardiovascular disease. Connecticut Children's team of oncologists, cardiologists and endocrinologists has developed a clinical practice guidelines to prevent and recognize early cardiovascular disease in pediatric cancer survivors. Dr. Orsey is testing their scoring system among childhood cancer patients from a database and in the clinic. She anticipates that the scoring system will allow doctors to standardize the way they treat patients so that cardiovascular disease is prevented or recognized and treated early in order to decrease heart disease in childhood cancer survivors.

Children treated for leukemia often have difficulty with school and learning. These children are also known to report sleep disturbances. With the MaxLove Project Fund St. Baldrick's Supportive Care Research Grant, Dr. Ruble is measuring sleep with a home monitor, and testing survivors for specific learning difficulties. She will then examine the relationship between sleep and cognitive function in this population. Dr. Ruble hopes in the future that this will allow researchers to design treatments for sleep disturbances that will ultimately help with learning and school.

The MaxLove Project Fund honors the survivorship journey of Max Wilford who was diagnosed with a brain stem tumor at the age of four. Despite several surgeries and an intense treatment protocol, Max is now able to be a “regular” kid due in large part to integrative therapies he received.

Survivors of childhood acute lymphoblastic leukemia (ALL) may have difficulty learning because of problems with attention and working memory caused by the medications they receive during the course of their leukemia treatment. The Georgia and the Peachy Keens St. Baldrick's Supportive Care Research Grant is determining if children would be willing to complete 25 computer-based training sessions (designed as games) over an 8-week period, at home, while they are taking oral chemotherapy medications. These computer games are designed to improve attention and working memory. If this study proves that children are willing to complete the training and participate in short (10- to 15-minute) evaluations of their attention and memory, Dr. Winick will then test this intervention with a larger number of children to see how well it works and how long any effects last.

This grant is named for the Georgia and the Peachy Keens Hero Fund which was created in honor of Georgia Moore’s 5th year past her cancer diagnosis. As a leukemia survivor, she inspires others to “just keep swimming” by raising awareness, hope and research dollars.

Our immune system has a remarkable ability to eradicate a vast array of foreign invaders. With increasing knowledge of this remarkable organ system, we can now begin to manipulate our immune system to fight cancer with remarkable precision and efficacy. However; tumor cells adopt multiple ways to reduce the immunotherapy efficacy, especially for solid tumors. Dr. Huang's research program systematically studies ways by which cancer cells evade immune cell detection and his goal is to develop a comprehensive, multi-pronged approach to increase the overall effectiveness of immunotherapy, particularly in pediatric and adolescent and young adult brain tumors and solid tumors.

Based on progress to date, Dr. Mulama was awarded a new grant in 2020 to fund an additional year of this Scholar grant. Kaposi sarcoma-associated herpesvirus is a virus that causes cancer known as Kaposi sarcoma, which is very common in HIV+ children, especially in Africa and sometimes in individuals who get an organ transplant. Dr. Mulama is designing and testing a vaccine that prevents and treats the viral infection, as well as antibodies to detect infection in people. He will also test the vaccine so that one day it can be used as a treatment to prevent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma in more than 40,000 patients worldwide each year.