Grants Search Results

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, and the Group 3 subtype is especially aggressive because it spreads early and often returns after treatment. Dr. Hu and colleagues will study a gene called SMARCD3, which normally helps guide how young brain cells grow, mature, and move to the right places as the brain develops. Dr. Hu believes Group 3 tumors hijack this normal developmental program to help cancer cells spread, and that lowering SMARCD3 may shift this tumor toward a less aggressive state. By studying SMARCD3 in models of brain development and tumor formation, Dr. Hu and colleagues will test whether targeting this pathway will reduce tumor spread and improve outcomes for children. This work is being completed under the mentorship of Dr. Baoli Hu.

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.

The survival rates for children with cancer remains unacceptable and the treatments for childhood cancers continue to carry significant life-altering side effects as most treatments do not specifically recognize cancer cells and affect healthy cells. Dr. Guerra and colleagues are developing a therapy created from the white blood cells of a patient's own immune system, known as immunotherapy. These cells are engineered to target cancer cells by engaging a marker that is present on the surface of cancer cells but not present on healthy cells. When the engineered white blood cells engage this cancer-specific marker, the cells become activated and attack the cancer cells while sparing healthy cells. Additionally, this immunotherapy can be boosted with further engineering approaches to remain active in a patient for long periods of time, allowing for long-term killing of cancer cells which we predict will improve survival while reducing treatment-related side effects.

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

Acute myeloid leukemia (AML) is an aggressive and molecularly heterogeneous cancer. Despite recent progress in developing new agents, front-line therapeutic protocols have not changed markedly over the past two decades and are associated with substantial morbidity and mortality. Accordingly, there is a need to develop novel mechanism-based treatments. Pediatric AML patients with NUP98 (nuclear pore complex protein 98) gene rearrangements (NUP98-r) have particularly dismal outcomes, with overall survival rates of 25-35%. Dr. Tian and colleagues are studying important proteins that contribute to a cell's ability to become cancerous in one of the most common types of NUP98-r AML: NUP98::KDM5A. Dr. Tian is also optimizing a compound's ability to directly inhibit KDM5A. Identification of these targets will allow for development of new drugs in the treatment of NUP98-r pediatric AML.

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

In some children with cancer, their bodies become severely inflamed and they develop a condition known as hemophagocytic lymphohistiocytosis, or HLH, which is often deadly. It is not yet understood why some children with cancer develop HLH and others do not. Dr. Meyer is using advanced technologies to carefully study blood cells from children with cancer who develop HLH. She is also working to create the first model of this disease so that she can better study the underlying disease mechanisms. By increasing our understanding of HLH, she seeks to develop strategies that will help doctors quickly identify affected children and determine which medicines are most effective. Her overall goal is to help more children survive this devastating condition. If successful, her findings will apply not only to HLH, but also to other life-threatening immune system disorders resulting from cancer and/or its treatment.

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

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.

Diffuse midline glioma is a devastating disease with no known curative therapy. New treatments using immunotherapy approaches, like CAR T therapy, show promise; however, tumors often escape detection by hiding their target proteins and suppressing the immune response to therapy. Dr. Pomaville seeks to tackle this problem by manipulating RNA modifications in the tumor and body to improve response to CAR T therapy. She has found that drugs that mediate RNA methylation, the most common modification on protein-coding mRNA, increases protein levels of existing CAR T antigens and can induce cell death. This RNA modification mark also influences how the body's immune system responds to tumors. Dr. Pomaville will test this drug in cell-line and immunocompetent models to assess whether manipulation of RNA methylation leads to improved efficacy of CAR T therapy. Dr. Pomaville and team will develop combination strategies that enhance the response to immunotherapy in patients.

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. 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. 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. 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. 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. 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. 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.

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. 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. Osteosarcoma is the most prevalent bone cancer in children, adolescents, and young adults, and survival rates are low when the cancer spreads or returns after treatment. Standard treatment for Osteosarcoma has been exclusively chemotherapy for decades, but many tumors have become resistant, allowing the cancer to come back even more aggressively. Dr. Pavisic and colleagues will study the cancer cells that survive chemotherapy and how well they spread to other parts of the body. Dr. Pavisic will examine whether two existing drugs, gefitinib and disulfiram, can stop these resistant cells from moving and growing. This research will better understand how resistance develops and will identify new ways to target the most dangerous cancer cells to improve treatment for children with Osteosarcoma. This work is being completed under the mentorship of Dr. Jovana Pavisic.