Funded Projects

Data Project Investigating HGG Immune Microenvironment During Tumorigenesis and Treatment in Primary Mouse Models

The funding for this project will generate ideal preliminary data to show that the project team has single nucleus and spatial RNA-seq data on their mouse models. This will provide “anchor data” to compare these models with human tumors, and identify gene signatures to test in the larger proposal when the mice are exposed to different therapies. Such preliminary data will greatly enhance the proposed NCI grant submission by showing feasibility and characterization of the models.

• Award $52,000 over 1 year (2022-2023)
• Principal Investigator Dr. Zachary Reitman, Duke Medical Center

DIPG National Brain Tumor Board

The National DIPG Tumor Board serves children and AYA patients diagnosed with a diffuse midline glioma including diffuse intrinsic pontine gliomas (DMG / DIPG). Significant advancements have been achieved over the past few years in understanding the underlying biology of this tumor type that have yet to be translated into better therapies. However, we now understand that despite a fairly homogenous clinical course, the molecular make-up of these tumors varies widely. Therefore, a tailored approach for each individual patient, with options constructed for their specific mutations and biomarkers identified by biopsy will be necessary to improve outcomes for these high-risk patients. Comprised of 30 experts from across the country, the board was formed as part of an FDA diagnostic trial and is intended to improve patient outcomes by providing collaborative direction from multiple consortiums with the availability of international collaboration. By offering an open access, collaborative tumor board for any child or young adult diagnosed with diffuse midline glioma, we will coordinate entry into precision clinical trials or compassionate care options early to: (i) improve care, (ii) increase progression-free survival time, (iii) increase outside survival outcomes, and (iv) significantly improve the quality of life of the affected patient and their families by guiding patients into coordinated trials. By coordinating weekly in our tumor board setting with our DMG specialists, we will have better information in real time concerning the progress of patients within the recommended trials in hopes of further coordinating trial and compassionate care options. Further, by allowing other medical professionals in the field to review the cases simultaneously with the tumor board, additional medical professionals will be mentored in diagnosis and treatment thereby increasing the likelihood that any child or young adult diagnosed with DMG will have improved care.

• Award $10,000 over 1 year (2022-2023)
• Principal Investigators Dr. Sabine Mueller, University of California San Francisco
• Funding Partners DIPG DMG Research Funding Alliance (DDRFA)

My DIPG Nurse Navigator Program

 When a child is diagnosed with brain cancer, parents and caregivers must quickly make critical decisions while navigating the shock of this devastating diagnosis. Getting up-to-date information about treatment options and side effects can be difficult, and families often find themselves alone in navigating immense physical, emotional, and financial challenges. Additionally, racial and socioeconomic factors make it harder to access resources like the clinical trials that are many families’ only hope. The new My DIPG Navigator (www.mydipgnavigator.org), is a free nurse navigator program designed to give families individualized, reliable guidance for the deadliest childhood brain cancer, DIPG (diffuse intrinsic pontine glioma)/DMG (diffuse midline glioma).

• Award $10,000 over 1 year (2022-2023)
• Project Lead Leslie Jared, RN, Chad Tough Foundation
• Funding Partners Funded in partnership with DIPG DMG Research Funding Alliance (DDRFA)

Low-Cost and Accurate Testing of High-Grade Brain Tumors

Pediatric high-grade gliomas and diffuse midline gliomas are devastating childhood brain tumors. Tumor sequencing can provide a more accurate diagnosis and prognosis for these tumors and has become increasingly important for proper disease management, clinical trial enrollment, and treatment response monitoring. Unfortunately, tumor sequencing takes too long (2-4 weeks) to immediately inform clinicians/patients and repeated tumor biopsy to adjust treatment strategy isn’t safe or feasible. This project addresses these issues with an interdisciplinary approach leveraging expertise in computer science and pediatric neuro-oncology. The first aim of this project is to use low-cost DNA sequencers and pHGG-focused assays to offer patients a more rapid molecular diagnosis. The second aim of this project is to reduce the need for lumbar punctures for serial tracking of tumor response in the clinic by using blood plasma samples instead of CSF. The samples will then leverage novel bioinformation error correction techniques to enable rapid, low-cost, accurate detection of tumor response directly from patient plasma.

• Award $130,000 over 1 year
• Principal Investigators Carl Koschmann, MD and Jack Wadden, PhD, University of Michigan
• Funding Partners Catching Up With Jack, Hope for Kids, and the Bradley Zankel Foundation

Brain Tumor Funders Collaborative's $3 Million Immunotherapy Initiative 

The Brain Tumor Funders Collaborative is comprised of leading nonprofits and private foundations united to improve survival and quality of life for brain tumor patients. The BTFC funds multi-disciplinary teams and encourages proposals that span childhood through adult age groups. The BTFC has pooled resources from six funders, including the PBTF, to invest in four immunotherapy projects that will help bridge the translational gap in brain cancer research. Each of these three-year projects will receive $750,000 grants from the BTFC. The PBTF’s participation in this highly collaborative funding endeavor further solidifies the group’s dedication to advancing immunotherapy research for the benefit of children and adolescents diagnosed with a brain tumor – ensuring that pediatric brain tumors are a research priority and fostering productive collaborations between researchers studying brain tumors in adults and children. It also presents the PBTF a remarkable and rare opportunity to multiply the impact of our $450,000 contribution to this large, strategic investment.

Novel Immune Mediated-Gene Therapy for Pediatric High-Grade Glioma

Pediatric high-grade glioma (pHGG) is a common form of highly aggressive pediatric brain cancer that accounts for the leading cause of death by disease among children in the United States. The University of Michigan Medical School’s Departments of Pediatrics and Neurosurgery have pioneered a treatment approach that uses gene therapy-mediated delivery of therapeutic genes into the tumor — utilizing a combination of viral vectors that express: (1) a gene that induces tumor cells’ death and (2) another gene that trains the patient’s immune system to recognize and kill any remaining tumor cells. The viral vectors are delivered into the tumor cavity or the remaining tumor mass post-surgery to trigger an effective anti-tumor immune response. This treatment strategy has been approved by the FDA for adult patients with glioblastoma multiforme, the most aggressive form of brain cancer, and a Phase I clinical trial has recently completed patient enrollment at the University of Michigan. The Pediatric Brain Tumor Foundation’s grant will fund the needed experimental work in pre-clinical models to study the impact of the H3G34R mutation in reprogramming the glioma immune microenvironment and get FDA approval to implement this therapy in children.

• Award $519,530 over three years
• Principal Investigators Maria G. Castro, PhD, R. C. Schneider Collegiate Professor of Neurosurgery, Professor of Cell & Developmental Biology at University of Michigan Medical School and Pedro R. Lowenstein, MD, PhD, Richard C. Schneider Collegiate Professor of Neurosurgery, Professor of Cell & Developmental Biology at University of Michigan Medical School
• Co-Investigator Karin Muraszko, MD, Chair and Julian T. Hoff, MD Professor, Neurological Surgery

Critical Mechanisms of Gene Regulation in Medulloblastoma

Medulloblastoma is a complex form of pediatric brain cancer, with recent research uncovering an entire series of previously unknown subtypes. This grant awarded by A Kids’ Brain Tumor Cure, now part of the PBTF, will use pioneering technology to reveal innovative treatment approaches critically needed for children with medulloblastoma. The studies conducted over this project’s two-year period will reveal the connection between and function of gene regulatory elements previously identified by Dr. Rivera’s lab as drivers of Group 3 medulloblastoma. This tumor subtype comprises 30% of all medulloblastoma cases and is associated with the poorest prognosis. Researchers will accomplish this by using new genomic and gene editing technologies to build 3D conformation maps of chromosomes/genomes from Group 3 medulloblastoma cells and directly test the function of key regulators of gene expression and their associated target genes.

• Award $300,000 over two years
• Principal Investigators Miguel N. Rivera, MD, Assistant Professor of Pathology, Massachusetts General Hospital
• Funding Partner Christopher Brandle Joy of Life Foundation

Project "DIPG All In"

When clinical testing of a drug begins, there can be significant gaps in knowledge or conflicting information about its basic biological performance. Securing additional funds to fill in these gaps is often challenging for labs; however, these gaps are important factors contributing to high drug failure rates in patients. Project “All In” for DIPG is a novel public-private partnership led by the National Cancer Institute to coordinate DIPG studies and better qualify drug candidates for clinical trials in children by facilitating more thorough evaluation. The project’s mission is two-fold: Establish and maintain a major effort to coordinate DIPG studies that will more efficiently and successfully advance DIPG therapies Establish a critical pipeline of therapeutic trials for all stages of the DIPG disease process. The PBTF’s Opportunity grant supports All In’s “intramural project fund” at NCI. This precedent-setting grant is specifically designed to distribute funding as project requests are received and reviewed. The fluidity in available funding will greatly reduce researchers’ grant-writing time – shifting the concern from “What grant can I get?” to “What work needs to be done?” This partnership also enables the PBTF to sit on the project’s Oversight Committee for evaluating funding requests. Being a part of it strengthens our expertise and insight into the research landscape at the national level.

• Award $100,000 over one year with the possibility of renewal
• Principal Investigators Kathy Warren, MD, Clinical Director of Pediatric Neuro-Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and Michelle Monje, MD, PhD, Stanford

Rapid Molecular Testing of High-Risk Pediatric Brain Tumors

Pediatric high-grade glioma (pHGG) and Diffuse Intrinsic Pontine Glioma (DIPG) are devastating childhood brain tumors with few patients surviving greater than 2 years. Over the last 2 decades the field has made great strides in uncovering the recurrent genetic drivers of these tumors through increasing use of molecular diagnostics (eg, DNA sequencing of tumor tissue). Sequencing can provide a more accurate diagnosis and prognosis and has become increasingly important for proper disease management and clinical trial enrollment for targeted therapies. Unfortunately, however, sequencing is far from optimized for clinical utility as turnaround time for tumor sequencing is typically 2 – 4 weeks and rarely available prior to radiotherapy or trial enrollment for agents given concurrently with radiotherapy. Furthermore, due to the risk of morbidity/mortality from repeat biopsy to track tumor mutations, it is not safe or feasible. To address these issues, this study takes an interdisciplinary approach to leverage a highly sensitive amplification technique currently being used in rapid COVID-19 diagnostics (LAMP) to enable rapid, low cost and low complexity detection of tumor mutations directly from the patient CSF and plasma. The outcome, if successful, will enable clinicians to more accurately and rapidly diagnose specific tumor mutations in order to recommend customized treatment options for the child’s specific tumor at the time of diagnosis and throughout the patient’s tumor journey, with little or no increased risk from complications due to invasive biopsies.

• Award $70,000 over one year
• Principal Investigators Jack Wadden, PhD, Carl Koschmann, MD, University of Michigan
• Funding Partner  Catching Up With Jack

Pacific Pediatric Neuro-Oncology Consortium, Operations Center

The Pacific Pediatric Neuro-Oncology Consortium, or PNOC, is a network of children’s hospitals formed to provide children with brain tumors access to clinical trials of innovative treatments. The mission of the PNOC is to pursue clinical strategies that capitalize on each patient’s tumor-specific molecular and genetic make-up. Each institution in the network has dedicated pediatric neuro-oncology research laboratories that lay the necessary groundwork to move quickly towards implementation of novel clinical trial concepts based on preclinical research. Each of the 15 participating hospitals also has the requisite multidisciplinary team of brain tumor specialists for optimal patient care and in-depth understanding of the needs of families and children suffering from this disease. The Operations Center coordinates the activities of the PNOC across all participating centers and clinical trial protocols and is an essential component for the overall success of PNOC.

• Award $500,000 over two years with the possibility of renewal for a third year
• Project leaders Michael Prados, MD, and Sabine Mueller, MD, PhD, University of California, San Francisco