Grants Search Results

MLL (Mixed Lineage Leukemia)-rearranged leukemias are one of the most prevalent childhoods leukemias and carries poor to intermediate prognosis. Current therapy is still inadequate for MLL-rearranged (MLLr) leukemias, highlighting the need to develop better therapeutics. A protein complex that helps to rearrange the packing of genomic DNA within the cell, the BAF chromatin remodeling complex, is vital for MLLr leukemia cell survival. In addition, loss of BAF complex has also been shown to boost anti-tumor immunity in previous published studies. Dr. Zhu and colleagues will target BAF complex leads to dual effects of eradicating leukemia cells, boosting anti-tumor immunity which synergizes to curb leukemia. Dr. Zhu and colleagues' research will identify a novel dual acting therapy for MLLr leukemia.

This grant is funded by and named for Emily Beazley's Kures for Kids Fund, a St. Baldrick's Hero Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

Rhabdomyosarcoma (RMS) is an aggressive childhood cancer that resembles developing muscle but cannot mature. The most dangerous form is driven by the PAX3::FOXO1 gene fusion, which forces uncontrolled growth. Better treatments are urgently needed because current therapy cures fewer than one in three children whose cancer returns. Dr. Khan and colleagues research targets FGFR4, a protein expressed at very high levels in RMS but not in normal tissues. A highly specific antibody against FGFR4 enables precise delivery of drugs into cancers. Dr. Khan and team will use this antibody in two ways: (1) to create an antibody-drug conjugate that delivers a drug blocking EP300, a key partner PAX3::FOXO1 uses to activate cancer genes: and (2) to build an antibody-PROTAC shuttle that brings a protein-destroying drug into FGFR4-positive cells to eliminate EP300. By disabling EP300 only in cancer cells, Dr. Khan and team will halt RMS growth while sparing healthy tissue and pave the way for safer, more effective treatments.

Year 1 of this grant is made possible in part, through funding from The Maddox Potter Foundation and is named in memory of Maddox, who is the inspiration for the Foundation. “Mad Dog” was a beautiful son, devoted big brother, diligent student and accomplished junior golfer. He fought alveolar rhabdomyosarcoma bravely for a year, and his final request was that someone, somewhere, would learn something from him. The Foundation is committed to honoring Maddox’s request by supporting families facing childhood cancer, funding critical research, and connecting the game he loved to hope, purpose, and philanthropy.

Dr. Ruff and colleagues will develop a targeted medical therapy for adamantinomatous craniopharyngioma, a brain tumor that affects children and causes lifelong vision loss, hormone problems, and cognitive impairment in the majority of survivors. Currently, the only treatments are surgery and radiation, which often cause irreversible damage to the developing brain, and despite this the tumor frequently comes back requiring repeated interventions. Combining two existing FDA-approved medications to shrink these tumors dramatically, Dr. Ruff and colleagues will study how likely these medications are to work in patients with this tumor. By analyzing tumor samples for the medication target and patient responses, Dr. Ruff and team will design a clinical trial that could transform care for children with this disease.

Despite advances in pediatric AML treatment, some leukemia cells can temporarily shut down and hide from therapy, later reawakening to cause relapse, the leading reason many cancers return after remission. Dr. Wang and colleagues seek to understand what allows these dormant leukemia cells to evade treatment and how they may eliminate them. Using gene-editing technology, Dr. Wang and team will work with a protein called DDX6, which acts as a key switch that keeps certain genes turned off in active leukemia cells. When DDX6 is lost, cancer cells enter a dormant, treatment-resistant state. This is a promising way to target these dormant cancer cells by blocking a signaling pathway called MEK which makes cells sensitive to chemotherapy. By uncovering how leukemia cells use dormancy to escape therapy and identify a way to target them, Dr. Wang and team's work will lay the foundation for new treatments to prevent relapse and improve long-term survival for pediatric AML patients.

Leukemia is a leading cause of death in children. Exciting new treatment strategies direct immune cells against B acute lymphoblastic leukemia (B-ALL) cells, however they are not effective for many patients, particularly those with relapsed disease. Why these therapies work in some children but not others is not understood. There is evidence that leukemia cells protect themselves by creating an environment around themselves (the immune microenvironment) that inhibits immune cells. Data indicates that B-ALL cells may impair a process called emergency myelopoiesis (EM), inhibiting normal immune cell function, if the leukemia cells express a protein called Siglec15. Dr. Porter and colleagues will determine if B-ALL impairs EM, whether that is dependent on Siglec15 and if EM can be restored to improve the immune response to leukemia cells. Dr. Porter and team will demonstrate that impaired EM plays an important role in the cell's development.

This grant is funded by and named for Emily Beazley's Kures for Kids Fund, a St. Baldrick's Hero Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

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.

Childhood leukemia happens when certain blood cells grow out of control. Dr. Wang'ondu and colleagues will focus on a protein called IKZF1, a transcription factor that helps young immune cells develop normally. In some children, IKZF1 is altered in a way that disrupts this process and makes leukemia more likely to form. Children whose leukemia has IKZF1 changes often have worse outcomes with current treatments. Dr. Wang'ondu will study how a specific change called IKZF1 N159Y disrupts normal immune cell functions and how Dr. Wang'ondu and team can target it with new types of drugs. Dr. Wang'ondu will work to understand how changes in transcription factors like IKZF1 cause leukemia and will help develop more effective treatments for children affected by these changes.

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 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. 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. 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. 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. 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. 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.