Grants Search Results

Dr. Kagami is developing LBSeq4Kids, a novel liquid biopsy test designed specifically for children with cancer. Traditional biopsies are invasive and only provide information from one point in time. In contrast, liquid biopsies use samples of body fluids - such as blood, spinal fluid, or fluid from the eye - to detect tumor DNA in real time. While this method is used in adult cancers, it is not widely available for children due to smaller sample volumes and the genetic variety of tumors. Dr. Kagami and colleagues are developing and clinically validating a three-part testing platform. LBSeq4Kids will help to better personalize treatment and monitor how a child's cancer responds to therapy. This project will also help determine which liquid biopsy tests and body fluids provide the most useful information for different cancers and stages of treatment. The goal is to improve diagnosis, guide more effective targeted therapies, and support better long-term outcomes for children with cancer.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Germ cell tumors can occur in children, adolescents, and young adults. Remarkably, these cancers begin in the fetus, before birth. About 10,000 new germ cell cancers are diagnosed annually in the US, and the incidence is increasing. An individual's genetic make-up, early development, and environmental exposures all affect the risk for germ cell cancer, but the underlying mechanisms are poorly understood, due in part to a lack of research models. Dr. Weiss and colleagues will use a model that accurately recapitulates germ cell cancers and will test how risk factors, including both genetic and developmental factors, promote germ cell cancers to study environmental factors like forever chemicals and pesticides that have been linked to increased germ cell cancer incidence. By testing risk factors and understanding how they act, Dr. Weiss and colleagues will identify new approaches to detect and prevent these cancers in pediatric and young adult populations.

Rhabdomyosarcoma (RMS) is a childhood cancer that affects muscle cells which attach to bones, affecting how a child moves, smiles, walks, and performs daily tasks. RMS can be very difficult to cure when it spreads. Children with metastatic or relapsed RMS have poor survival, and current treatments often cause serious long-term side effects including second cancer. New, safer therapies are urgently needed. Dr. Chen and colleagues will work with a gene called BRD1, which helps RMS cells move and invade other tissues. BRD1 controls another gene, MYOG, which is abnormally active in this cancer. When either gene is reduced, RMS cells become much less able to spread. Dr. Chen and colleagues will uncover how BRD1 and MYOG work together to drive metastasis and will identify the genes they regulate to serve as new drug targets. By revealing a new biological pathway that supports tumor spread, Dr. Chen and team will lay the foundation for more effective, less toxic treatments for children with high-risk RMS.

Neuroblastoma (NB) is a common and deadly solid tumor in children, and despite receiving the most intensive treatments available, 50% of all children with high-risk disease die from this cancer. NB is aggressive in part because it has high levels of chemicals called polyamines (which are made from arginine/ARG). A drug called difluoromethylornithine (DFMO), blocks polyamine production. Dr. Turn and colleagues combine DFMO with decreased ARG to cure 1/3 of models with NB without using chemotherapy in their research. There are however, remaining tumors that have increased macrophages. Although macrophages can eat cancer cells, many of these macrophages are hijacked to help the tumor to grow despite decreased polyamines. Dr. Turn and colleagues will learn how macrophages do this and will find ways to target them to improve this therapeutic strategy in NB.

This grant is funded by and named for 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.

Dr. Shen will develop a new immune-based approach to treat diffuse midline glioma, a deadly childhood brain tumor with very limited treatment options. Dr. Shen and colleagues' work will focus on helping the body's natural killer immune cells better recognize and destroy tumor cells while sparing healthy brain tissue. Dr. Shen will test whether standard radiation therapy can make tumor cells more visible to these immune cells, thus improving treatment effectiveness and safety. Dr Shen's research will lay the groundwork for a more precise and less toxic therapy for children with this devastating disease.

This grant is funded by and named for Luke's Army Pediatric Cancer Research Fund. This Hero Fund was created in memory of Luke Ungerer who brought smiles and sunshine wherever he went with plenty to share with everyone. He battled a brain tumor with a positive spirit and inspired others with his courage in his short life. This fund intends to carry on Luke’s legacy of positivity with the hope that it will ripple across many lives for many years to come.

This year, neuroblastoma will account for approximately 15% of cancer-related deaths in children. Despite recent advances in treating high-risk neuroblastoma, nearly half of patients will relapse with no curative treatments. Thus, safe and effective treatments are urgently needed. Using recently developed tools to find new therapy targets at a large scale, Dr. Mabe and colleagues understand that neuroblastoma tumors require polycomb repressive complex 1 (PRC1). Dr. Mabe and colleagues will identify that a new class of drugs that blocks PRC1 activity can reduce neuroblastoma tumor growth. To determine the exact mechanism by which these drugs reduce neuroblastoma growth, Dr. Mabe's lab will apply sequencing technologies to assess how PRC1 changes the neuroblastoma tumors to become less like a cancer cell and more like nerve cells.

Dr. Boelens and colleagues will study how the immune system recovers after a bone marrow transplant in children with leukemia. These transplants can cure cancer, but some children relapse or develop a serious complication called chronic graft-versus-host disease, where the donor immune system attacks the child's tissues. Dr. Boelens and team will focus on the thymus, an organ that trains new immune cells but is easily damaged by chemotherapy and radiation. Dr. Boelens and colleagues will measure how well the thymus works and how immune cells grow during the first year after transplant. Dr. Boelens will confirm their findings by working with many hospitals through a large pediatric transplant network. By finding early warning signs of poor recovery, Dr. Boelens and colleagues will help doctors identify children at high risk and guide more personalized care so that more children survive transplant and grow up healthy, with fewer long-term complications.

Relapsed/refractory pediatric acute myeloid leukemia (AML) is a challenging disease with poor survival. Combining two classes of drugs--thalidomide analogs (TAs) and menin inhibitors- may improve outcomes for patients with a particular genetic subtype of AML. Dr. Li has shown that TAs can affect the numbers and activity of a type of immune cell called regulatory T cells (Treg), which can prevent the immune system from recognizing and attacking leukemia cells. Treating pediatric AML patients with TAs and menin inhibitor, which is being tested in an upcoming clinical trial, may impair Treg activity and improve immune recognition and targeting of AML, potentially contributing to responses. Dr. Li will study the effects of combination therapy on models. Dr. Li's study will improve the efficacy and safety of new pediatric AML therapies by defining their effects on immune responses.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

This grant funds a student to complete work in pediatric oncology research for the summer. In African-Americans, an evolutionary mechanism that protects against malaria parasites also causes lower infection-fighting white blood cells (WBC) compared to the general population. This low WBC is called the "duffy null phenotype" (DNP). However, this has been associated with practices that disadvantage certain groups in healthcare, including unnecessary referrals for low WBC, obstacles to enrolling on clinical trials, and unneeded and invasive tests. Treatment for childhood leukemia includes medicines that can slow down the bone marrow, and prevent too many toxicities from treatment. Dr. Wolfson and colleagues plan to carry out a study to see if African-American children with DNP get less chemotherapy due to low WBC compared to children without DNP. This work is being completed under the mentorship of Dr. Julie Wolfson.

This grant funds a student to complete work in pediatric oncology research for the summer. Atypical teratoid rhabdoid tumors (ATRT) are extremely aggressive brain tumors that most often affect children under age 3. Current ATRT treatment involves medications that can lead to bad side effects. There is a need to understand more about ATRT biology to improve the outcomes for these patients. Dr. Tsai and colleagues have found that blocking a nuclear export protein leads to ATRT cell death. A nuclear export protein carries other proteins and RNA cargo from the nucleus out to the cytoplasm of the cell. It is known that blocking this process results in cargo getting stuck in the nucleus, however, the identity of these cargo proteins and RNA is not known. Dr. Tsai and team will utilize methods to separate proteins and RNA from the nuclear and cytoplasmic compartments of ATRT cells. Identifying these cargo will allow for understanding of why blocking nuclear export kills ATRT cells, and will give insight into other strategies for targeting these tumors. This work is being completed under the mentorship of Dr. Jessica Tsai.

This grant funds a student to complete work in pediatric oncology research for the summer. Dr. Flatt treats and studies acute lymphoblastic leukemia (ALL), the most common childhood cancer, in a clinic that is dedicated to Hispanic children. Most children with ALL have a protein called TdT, which helps doctors diagnose the disease. When TdT is missing, leukemia is often harder to treat. Dr. Flatt's team has found that children in Mexico have TdT-negative leukemia more often than other groups, and many families work or live near farms where pesticides (chemicals used to kill insects/weeds) are used. Dr. Flatt and colleagues will test whether common pesticides can cause leukemia cells to lose TdT and make them more resistant to chemotherapy. This work is being completed under the mentorship of Dr. Terrie Flatt.

This grant funds a student to complete work in pediatric oncology research for the summer. Acute Myeloid Leukemia (AML) is a cancer in which harmful blood cells grow out of control and crowd out healthy cells that the body needs. The immune system is usually able to remove unhealthy cells, but these harmful blood cells are especially good at hiding and continuing to grow. Natural killer cells are an important part of the immune system and act like security guards that clear away dangerous cells. Dr. Wiita and colleagues will modify and improve natural killer cells so that they are better at finding and destroying harmful blood cells in AML. Dr. Wiita and colleagues will provide safer, stronger, and longer lasting treatments for AML patients. This work is being completed under the mentorship of Dr. Arun Wiita.

This grant funds a student to complete work in pediatric oncology research for the summer. Neuroblastoma is an aggressive cancer that often spreads quickly and contributes to 15% of cancer-associated deaths in children. Dr. Feng and colleagues will use models of neuroblastoma to study how a metabolic enzyme called DLST changes the way tumors grow and communicate with immune cells. Dr. feng's team will increase the DLST amount in tumor cells and use fluorescent imaging to track immune cells and measure tumor size over time. By understanding how tumor metabolism shapes immune responses, the team will identify new strategies to help treat children with neuroblastoma. This work is being completed under the mentorship of Dr. Hui Feng.

This grant funds a student to complete work in pediatric oncology research for the summer. Many children who survive cancer later develop serious heart and blood vessel problems caused by the treatments that saved their lives. Dr. Sarosiek and colleagues will study why heart and blood vessel cells in children are more sensitive to radiation and chemotherapy than those in adults. Dr. Sarosiek and team will examine proteins inside these cells that control whether a cell lives or dies and determine why younger cells are more likely to be pushed toward cell death during treatment. By understanding this difference, Dr. Sarosiek will find ways to protect healthy vascular and heart tissues in children while still allowing cancer therapies to effectively destroy tumors. This work is being completed under the mentorship of Dr. Kristopher Sarosiek.

This grant funds a student to complete work in pediatric oncology research for the summer. The overall goal of this project is to assess the ability of small molecule inhibitors of the EYA proteins, XPO1, and Menin to slow the growth of leukemia cells in the petri dish. Dr. Aumann and colleagues will assess the ability of these inhibitors to work by themselves and in combination with each other. Dr. Aumann and team will work to see a "better together" effect –-i.e where two agents used in combination cause more cell death than either would alone -a phenomenon known as synergy. This work is being completed under the mentorship of Dr. Waitman Aumann.

This grant funds a student to complete work in pediatric oncology research for the summer. Medulloblastoma is the most common malignant brain tumor in children, often recurring due to treatment resistance. The MYC oncogene is central to tumor growth and response by regulating gene expression, but how therapy resistance affects MYC's function in medulloblastoma remains unclear. Dr. Prensner and team will conduct research aimed at studying MYC by mapping MYC's genomic binding sites. The team will measure changes in gene programs controlled by MYC by using cell models that are sensitive and resistant to therapy. Key techniques will include chromatin immunoprecipitation (ChIP) and RNA sequencing to identify genes MYC activates in resistant cells. Understanding how MYC reprograms gene expression to drive resistance will help identify new targets to improve therapy and outcomes for affected children. This work is being completed under the mentorship of Dr. John Prensner.

This grant funds a student to complete work in pediatric oncology research for the summer. Metastatic disease is the primary cause of death in neuroblastoma (NB) patients, yet our understanding of mechanisms controlling it remain poorly understood. Half of all NB patients are metastatic at diagnosis and commonly metastasize to the bone marrow. Recent transcriptional analysis suggests that several types of immune cells are critical for metastasis formation in the bone marrow. The MYCN_TT model efficiently metastasizes to the kidney marrow, making it an effective model to study the bone marrow metastatic microenvironment. Dihydrolipoamide S-succinyl transferase (DLST) has been shown to increases metastatic disease in MYCN_TT. Dr. Anderson and colleagues will define how metastatic infiltrate influences the kidney marrow and how DLST alters the kinetics of the metastatic cascade to promote metastasis in NB. This work is being completed under the mentorship of Dr. Nicole Andersen.

This grant funds a student to complete work in pediatric oncology research for the summer. Ewing sarcoma is driven by an abnormal "fusion" protein called EWS-FLI1 that turns many genes on and off incorrectly. Dr. Leggas and colleagues are developing therapies that disrupt EWS-FLI1, makeing these treatments safer and more effective by identifying new weaknesses that appear when EWS-FLI1 is turned off. Dr. Leggas and team will measure how Ewing sarcoma cells change their metabolism, meaning how they make energy and key building blocks, after EWS-FLI1 is blocked or degraded resulting in guiding future combination therapies that will improve tumor control while reducing toxicity. This work is being completed under the mentorship of Dr. Markos Leggas.

This grant funds a student to complete work in pediatric oncology research for the summer. Pediatric kidney tumors make up almost a tenth of all childhood cancers and represent a range of diseases that require different treatments. Surgical biopsy or resections are currently necessary to diagnose these cancers but can inadvertently cause disease spread and are invasive procedures. Dr. Crompton and colleagues will work to detect and profile tumor DNA in the blood from children with renal tumors using less invasive methods for detection and diagnosis to improve the upfront management of patients with newly discovered kidney masses. This work is being completed under the mentorship of Dr. Brian Crompton.

This grant funds a student to complete work in pediatric oncology research for the summer. Children with aggressive neuroblastoma tumors have poor cure rates despite intensive treatment, and new therapies are needed. Seriniquinone is a new chemical compound isolated from bacteria collected from the bottom of the Pacific Ocean that has been found to be effective against adult cancer cells. Dr. Zage and colleagues will test seriniquinone to determine its effectiveness against neuroblastoma cells and tumors, and will evaluate cells before and after treatment with seriniquinone to determine how it kills neuroblastoma cells identifying specific genes and proteins that are important for neuroblastoma cell responses and resistance. This will determine whether and why seriniquinone is effective against neuroblastoma, leading to clinical trials using new drugs isolated from previously untested sources for treatment of children with neuroblastoma. This work is being completed under the mentorship of Dr. Pete Zage.