Other Research Funding

Award: $60,000 over 1 year (2022-2023)
Principal Investigators:  Dr. Anahita Fathi Kazerooni, Instructor Center for Data Driven Discovery in Biomedicine at Children’s Hospital of Philadelphia
Funding Partners: Tough2Gether for DIPG/DMG and Elle’s Angels Foundation as part of the DIPG DMG Research Funding Alliance

This project seeks to predict tumor response to treatment and progression in patients with DMG/DIPG by using volumetric measurements obtained via automatic deep learning brain tumor segmentation.  This method intends to create a 3D model to replace the current 2D methods of measurement by using AI methods and widely available MRIs. This project is using AI (an algorithm that Dr. Kazerooni has created) and machine learning for diagnostics, prognosis, and out come, response to treatments. This will run automatically on any scan to give the RAPNO (Response Assessment in Pediatric Neuro-Oncology) info to the clinicians.

Award: $130,000 over 1 year (2022-2023)
Principal Investigators: Dr. Carl Koschmann/Dr. Jack Wadden, University of Michigan Medical Center

This project will optimize a number of wet-lab and computational aspects of an electronic sequencing pipeline which was recently established. By using low-cost DNA sequencers and pHGG focused assays, we will offer patients a more rapid molecular diagnosis (<1 day) to allow prompt enrollment in the most relevant clinical trials and enable practical CSF-based treatment response monitoring over the course of treatment. The project will also reduce the need for lumbar puncture for serial tracking of tumor response in clinic using blood (plasma) samples. Based on the lab’s recently completed prior work showing that tumor DNA shed into spinal fluid can be used for diagnosis and prediction of long-term treatment response. The team will leverage a highly-sensitive amplification technique—LAMP [2]—currently being used in rapid COVID-19 diagnostics (LAMP) along with a novel bioinformatic error correction technique to enable rapid, low-cost, accurate detection of tumor response directly from patient plasma.

Award: $105,000 over 1 year (2022-2023)
Principal Investigators: Dr. Annie Huang, Sick Kids of Toronto
Funding Partners: Blake Vince Payne Star Fund

This project combines CRISPRi technology with a Zebra Fish brain tumor model to uncover key druggable pathways for RB1/MYC driven infant Pineoblastoma.

Award: $100,000 over 1 year (2022-2023)
Principal Investigators: Dr. Paul Northcott, St. Jude Medical Center
Funding Partners: Blake Vince Payne Star Fund

This project is developing preclinical models of high-risk pineoblastoma subgroups and using them to identify therapies designed for the specific biology of these brain tumors.

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

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:$64,000 over 1 year (2022)
Principal Investigators: Dr. Quinn Ostrom, Duke Medical Center; Carol Krutchko. Central Brain Tumor Registry of the United States (CBTRUS)

Brain tumors are the most commonly diagnosed and deadliest form of childhood cancer in children and adolescents 0-19. Yet little is reported on these types of cancer.  The Pediatric Brain Tumor Foundation funded a first-of-its-kind report to provide a statistically relevant and more accurate depiction of the incidence and impact of brain tumors in children and adolescents in the United States. The Central Brain Tumor Registry (CBTRUS) is the largest aggregator of cancer registry data on brain and other CNS tumors in the US and provides the most complete picture of population-based data for children and adolescents diagnosed with a brain tumor. Read the results of this report here.

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

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)
Project Lead: Leslie Jared, RN, Chad Tough Foundation
Funding Partners: Funded in partnership with DIPG DMG Research Funding Alliance (DDRFA)

 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: $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

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.

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.

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
Funding Partner: Samson Research Fund with funds raised through Hope for Kids

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: $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

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: $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
Funding Partner: PLGA Fund at PBTF

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: Adam Resnick, PhD, Children’s Hospital of Philadelphia (CHOP), Javad Nazarian, PhD, Children’s National Health System, Benjamin Garcia, PhD, University of Pennsylvania
Funding Partners: CJR Memorial Foundation, PLGA Fund at PBTF

This multi-institutional Project Open DIPG study uses state-of-the-art technology to determine the potency of candidate drugs belonging to the novel class of molecules called HDAC inhibitors.

This grant enables researchers to:

• Compare the treatments’ effects on its own versus in combination with other types of treatments
• Study the cancer cells’ molecular functionality at the DNA and protein levels
• Determine animal model survival rates and duration

Project Open DIPG is a joint venture by the Pacific Pediatric Neuro-Oncology Consortium, a previous PBTF Opportunity Grant awardee, and the Children’s Brain Tumor Tissue Consortium.

The research builds on PNOC’s clinical trial portfolio through biospecimen collection, genomic sequencing, and an experimental animal model systems approach supported by CBTTC. The tissue samples will be added to CBTTC’s biorepository, and data from preclinical drug testing in DIPG tumor samples will be deposited into the CAVATICA platform.

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

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: $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

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:$234,000
Project leaders: Bob Carter, MD, PhD, University of California, San Diego; Stephen Albert Johnston, PhD, Arizona State University; and Robert Wechsler-Reya, PhD, Sanford Burnham Prebys Medical Discovery Institute
Cofunder: ABC2 (Accelerate Brain Cancer Cure)

Antibody-based profiling shows promise as a general approach to diagnosis and as an indicator/biomarker of response to treatment. Researchers have developed a novel technology platform to detect patterns of tumor-recognizing antibodies, or immunosignatures, that differ by tumor type and disease state.

Using this platform, researchers will assay human tumor and blood samples to define signatures that correlate with each of the four molecular subtypes of medulloblastoma. Simple blood tests analyzing these immunosignatures patterns have already been shown by Dr. Johnston’s lab to recognize different types of adult brain cancer.

In specialized laboratory models of medulloblastoma, researchers will test the utility of the immunosignatures as dynamic biomarkers for early detection of tumor growth/relapse and of tumor responsiveness to drugs. The tumor-associated proteins that elicit the immunosignatures will also be identified, thereby uncovering candidate targets for novel therapies for medulloblastoma.

Project leader: Peter Adamson, MD, Chair, Children’s Oncology Group, Alan R. Cohen Endowed Chair in Pediatrics at the Children’s Hospital of Philadelphia
Award: $100,000

The Children’s Oncology Group (COG) unites more than 9,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities and cancer centers across North America and other continents in the fight against childhood cancer.

The COG’s Project:EveryChild is an initiative that will create a fundamental platform for translational research. The initiative involves taking extra tissue available from children who must undergo a diagnostic procedure and then storing samples in COG’s state-of-the-art biorepository which serves as a worldwide resource. Laboratories studying these tumor tissue samples can then link clinical data from each child, such as the treatment the child received and how effective it was, as their research moves forward. Project:EveryChild will result in a well annotated childhood cancer biobank to enable robust discovery research and a platform for personalized medicine.

The study is open to all children diagnosed with cancer. Funding from the PBTF specifically supports the acquisition of follow-up clinical information and central nervous system (CNS) tumor biospecimens. The costs of obtaining the biospecimens and corresponding clinical follow-up data obtained at diagnosis or relapse from children with brain tumors are often not covered by grants from the National Cancer Institute.

Award: $150,000
Project leader: Rameen Beroukhim, MD, PhD, Dana-Farber Cancer Institute
Funding Partner: Christopher Brandle Joy of Life Foundation

In approximately 25 percent of medulloblastoma cases, tumor growth is driven by the amplification of a gene called MYC. The majority of children with MYC-amplified medulloblastoma die of their disease. Other pediatric cancers that harbor amplifications of MYC family members, notably neuroblastoma, are also similarly associated with devastating outcomes. Novel therapeutic strategies are desperately needed in the clinic for children with these cancers. Experience with novel agents, however, has shown that cancers frequently evolve to become resistant. A promising therapeutic approach is to develop combination treatments that include drugs to overcome or circumvent the development of resistance. In laboratory studies, Dr. Beroukhim has shown that MYC- amplified medulloblastomas are sensitive to a class of chromatin modifiers called BET-bromodomain inhibitors. The specific aims of his proposal are to fully elucidate the mechanism of action of this family of inhibitors and thereby gain insight into the genes and proteins that confer resistance. His results will guide strategies to optimize the efficacy of BET-bromodomain inhibitors for children with MYC-amplified medulloblastoma and provide a framework to study cancer’s evolution in response to this novel class of cancer drugs.

Award: $1,000,000 over three years
Principal investigators: James T. Rutka, MD, PhD, FRCSC and Michael D. Taylor, MD, PhD
Institution: The Hospital for Sick Children, Toronto, Canada
Funding partner: Meagan’s Walk Foundation

The principal investigators started a worldwide consortium, GENE (Global Ependymoma Network of Excellence) consisting of scientists, pathologists and clinicians from more than 30 centers around the world. Cumulatively, the members have contributed more than 400 PF-ependymomas with matched clinical data to the tumor bank in Toronto.

With funding from the PBTF, the PIs will continue to grow the tumor bank and develop biomarkers to discern PFA (poor prognosis) from PFB (better prognosis) ependymoma in a CLIA-certified manner. They will also develop additional human PFA xenograft models to study epigenetic agents for therapy and to study biology and response to novel agents in the relapse setting.

Principal investigators: John Sampson, MD, PhD, MBA, Oren Becher, MD and Kendra Congdon, PhD
Institution: Duke University
Award: $400,000 over three years

Immunotherapy promises an exquisitely precise approach to treatment. However, it is limited in this role due to a lack of consistently expressed and tumor-specific antigens. Recently, a point mutation was discovered that provides a highly conserved and tumor-specific mutation, H3.3K27M, in 60 percent of DIPGs. Research objectives are to maximize immunogenicity of an H3.3K27M-containing peptide, to optimize vaccination timing in combination with radiation therapy in a murine model of H3.3K27M positive DIPG, and to perform IND-enabling studies.

Award: $200,000 over two years
Principal investigators: Eric Thompson, MD
Institution: Duke University
Funding Partner: Catching up with Jack

Recent findings have shown that cytomegalovirus (CMV) antigens are expressed in 92% of medulloblastoma cases. Targeting CMV antigens through peptide vaccination is therefore a candidate treatment strategy for this type of brain tumor. This novel strategy will be tested in a pilot clinical trial of a rationally-designed vaccine formulation containing multiple CMV peptides. The trial will enroll children with recurrent medulloblastoma and the primary goals are to determine safety and immunogenicity.

Award: $300,000 over three years
Principal investigators: Arturo Alvarez-Buylla, PhD and David Rowitch, MD, PhD
Institute: University of California, San Francisco

To better understand pediatric glioma origins, it is important to determine the precise stages of oligodendrocyte progenitor cell (OPC) development targeted by oncogenic mutations. The broad objective of this proposal is to use the methylome as a new index of oligodendrocyte developmental character and use this data to interrogate OPC-like character across different subtypes of human pediatric gliomas from brain stem and forebrain.

Award: $300,000 over three years
Principal investigators: Sabine Mueller, MD, PhD, Nalin Gupta, MD, PhD and Joseph Costello, PhD
Institution: University of California, San Francisco

Mutations in the gene encoding for histone H3.3 (K27M and G34V/R) have been reported as molecular drivers in pediatric HGGs. Moreover, the presence of K27M mutation correlates with worse clinical outcome. PIs will perform whole exome sequencing and gene expression profiling of tumor tissue from children newly diagnosed with DIPG to explore the genomic heterogeneity and to identify key alterations associated with treatment resistance and progression. This clinical feasibility study is being conducted through the Pacific Pediatric Neuro-Oncology Consortium.

Award: $150,000 over three years
Principal investigators: Nalin Gupta, MD, PhD and Susanna Rosi, PhD
Institution: University of California, San Francisco

Radiotherapy can cause late effects including progressive cognitive dysfunction. The activation of inflammatory pathways that occur along with tumor recurrence and after cranial irradiation produce many adverse effects, and no treatment is effective. The experiments proposed in this project will help provide a detailed understanding of macrophage accumulation in a rodent brain tumor model, and how modulating this response may affect cognitive performance.

Award: $150,000 over three years
Principal investigators: David Rowitch, MD, PhD and William Weiss, MD, PhD
Institution: University of California, San Francisco
Funding partner: Bryan’s Dream Foundation

The Rowitch laboratory has shown that oligodendrocytes maintain a Wnt-activated program of angiogenesis at postnatal stages (Yuen et al., 2014, Cell in press). Moreover, many laboratories have shown conservation of oligodendrocyte-like features in human glioma. Therefore, PIs will test the hypothesis that gliomas have co-opted a mechanism for angiogenesis that is normally required during CNS development. This study may identify a novel target for anti-angiogenic therapy.

Award: $300,000 over three years
Principal investigators: Roger McLendon, MD and Stephen Keir, DrPH
Institution: Duke University
Funding partner: The Kyrie Foundation

Funding from the PBTF to the Biorepository Core provides for light microscopic and molecular analysis on all banked specimens in order that researchers have access to histologically and genotypically characterized tumor samples for diagnostic assessments in preclinical and clinical studies. In addition, funding supports ongoing development of pediatric brain tumor cell lines and patient-derived xenografts at Duke that enable the study of phenotypic and functional heterogeneity, the characterization of tumor subtypes, and preclinical drug testing. The resources of the core facilities are made available to researchers at Duke and other institutions.

Award: $100,000 over three years
Principal investigators: Joanna Phillips, MD, PhD and Theodore Nicolaides, MD
Institution: University of California, San Francisco

Biospecimens obtained directly from the operating room during pediatric brain tumor resections are acquired, molecularly characterized and used to establish tumor cell lines and intracranial xenografts. These core resources, developed and maintained on an ongoing basis, are invaluable to help detect new therapeutic targets and to test novel therapies in animal models of the disease, guiding and improving future clinical therapies in pediatric brain tumor patients. The resources of the UCSF core facility are an essential component of the UCSF Brain Tumor Research Center. They are also made available to researchers at other institutions.