ChadTough Defeat DIPG Foundation’s Latest Grants

ChadTough Defeat DIPG Foundation funds the most promising childhood brain cancer research across the globe. To date, the foundation, along with their partners and donors, has funded over 65 researchers, across 35 institutions, totaling $27 million.

Sneha Ramakrishna
2023 New Investigator Grant Recipient
Stanford University

Immune Determinants of GD2 CAR T-Cell Activity in Patients with DIPG

Co-funded by the Violet Foundation for Pediatric Brain Cancer and Tough2gether Against DIPG/DMG

CAR T-cell therapy has shown success in treating certain types of cancer in children. This therapy trains the immune system’s T cells to locate and eliminate cancer cells. However, until recently, CAR T-cell therapy was not available for children with brain tumors like DIPG. In 2021, Stanford doctors, including Dr. Ramakrishna, initiated a clinical trial to use CAR T-cells for treating DIPG in children and young adults. Encouragingly, 10 out of 12 patients who received these CAR T-cells experienced tumor shrinkage and improvement in symptoms. This project aims to gain insights from patients to understand why CAR T-cell therapy succeeded or failed, with the aim of enhancing and optimizing the treatment.

John Prensner
2023 New Investigator Grant Recipient
University of Michigan

Targeting Aberrant RNA Translation in DIPG

Co-funded by the Violet Foundation for Pediatric Brain Cancer

In all cancers, certain genes become overactive to fuel their growth and aggressiveness. To function properly, genes need to convert their DNA code into a temporary form called RNA, which serves as a template for producing proteins that carry out cellular functions. In DIPG, many of the genes responsible for cell growth disrupt the normal process of RNA translation, leading to the production of unintended protein products. Through this project, Dr. Prensner proposes that targeting this abnormal RNA processing could be a vulnerability in DIPG that can be exploited for treatment. This research will be the first systematic exploration of this abnormal RNA translation in DIPG and will link it to different known genes involved in driving the disease.

SandroMatosevic (1)
Sandro Matosevic
2023 New Investigator Grant Recipient
Purdue University

Reprogramming the Tumor Microenvironment in DIPG with Engineered iPSC-NK Cells to Improve Immunotherapy

Co-funded by the Violet Foundation for Pediatric Brain Cancer

This project aims to develop a powerful and innovative immunotherapy using induced pluripotent stem cell (iPSC)-derived NK cells. These engineered NK cells aim to eliminate DIPG and enhance the activity of other immune cells against the tumor. Dr. Matosevic intends to demonstrate that combining iPSC-engineered NK cells with strategies to disrupt the DIPG TME will challenge current treatment approaches and revolutionize the way we treat DIPG.

JohnLigon (1)
John Ligon
2023 New Investigator Grant Recipient
University of Florida

Defining the Tumor Intrinsic and Regional Landscape of Therapeutic RNA-Nanoparticle Transduction and Immune Activation Following Intravenous Administration in DIPG

Dr. Ligon and his team have developed a new treatment called RNA nanoparticle vaccines (RNA-NPs) to combat DIPG and other cancers. These personalized vaccines stimulate the body’s immune system to recognize and eliminate cancer cells. The treatment has shown promise in clinical trials for adult brain cancer patients, and now they plan to extend the trials to children with a different type of brain cancer, as well as patients with melanoma (skin cancer) and osteosarcoma (bone cancer). Encouraging initial results suggest that RNA-NPs could also be effective against DIPG. This project aims to further investigate the potential of RNA-NPs for treating children with DIPG and gain a better understanding of their effectiveness across various cancer types.

Lily Keane
2023 New Investigator Grant Recipient
University Cork College

Identifying and Targeting Developmental Vulnerabilities of Diffuse Midline Gliomas

DMG is characterized by a specific mutation called H3K27M. This mutation affects a group of proteins known as polycomb repressive complexes 2 (PRC2), which play a vital role in determining cell development. The goal of this project is to gain a deeper understanding of PRC2’s role in the normal development of the pons, a critical part of the brain. Specifically, Dr. Keane will study cells with increased PRC2 activity and examine their DNA to identify any changes that occur when PRC2 activity is heightened. Additionally, she will investigate the presence and role of immune cells in the pons during this crucial time, examining how they contribute to the growth and expansion of this vulnerable region.

Sabine Mueller & Pavithra Viswanath
2023 Game Changer Grant Recipient
University of California, San Francisco

In Vivo Imaging of Diffuse Midline Gliomas

Co-funded by the Violet Foundation for Pediatric Brain Cancer

DMGs are brain tumors that often spread diffusely, making it challenging to track their progression. Current methods rely heavily on MRI scans, which do not always provide accurate information about treatment response. Dr. Viswanath and Dr. Mueller have discovered that changes in deuterated glucose metabolism can be observed within five days of radiotherapy in mice with DMGs, even when MRI scans show no visible alterations. In this study, they aim to investigate whether deuterated glucose can be used to visualize active tumor tissue and serve as an early indicator of therapy response in DMG-bearing mice.

Bilal Omer
2023 Game Changer Grant Recipient
Baylor College of Medicine

C7R-GD2 CAR T-Cells for DMG: Clinical Trial of Dual Route Strategy

Co-funded by the Violet Foundation for Pediatric Brain Cancer

New research has shown that 80% of DMG cases exhibit high levels of a protein called GD2. To target GD2, scientists are utilizing immunotherapy to destroy cancer cells. Dr. Omer and his team have improved the effectiveness of the GD2-targeting CAR T-cells by incorporating an additional gene, C7R, which enhances their anti-tumor capabilities and extends their lifespan. So far, they have treated 12 patients, with two experiencing tumor reduction exceeding 50%. To further enhance the therapy’s effectiveness, they plan to attack the tumor from multiple angles by administering CAR T-cells intravenously and directly into the spinal fluid surrounding the brain and spine.

RobbieMajzner (1)
Robbie Majzner
2023 Game Changer Grant Recipient
Stanford University

Engineering Enhanced GD2 CAR T-Cells to Overcome DIPG Immune Resistance

Co-funded by the Violet Foundation for Pediatric Brain Cancer and the SoSo Strong Pediatric Brain Tumor Foundation

This project will build on Dr. Majzner’s experience treating children with DIPG with CAR T-cells. Several patients have developed significant responses,  however, some showed only temporary improvement or did not respond at all. Through this project, Dr. Majzner and his team aim to test and validate a new type of GD2 CAR T cell that is capable of enhanced persistence and anti-tumor efficacy, providing a more effective strategy for treating patients with DIPG/DMG.

Akash Deogharkar
Akash Deogharkar
2023 Fellowship Grant Recipient
University of Michigan

Targeting Combined Metabolic and Epigenetic Pathways H3K27M DIPG

Mentor: Sriram Venneti

Ryan Duchatel
2023 Fellowship Grant Recipient
University of Newcastle

Integrating Systemic and Local Therapeutic Vulnerabilities to Improve the Treatment of Diffuse Midline Glioma

Mentor: Matt Dun

Pruthvi Gowda
Pruthvi Gowda
2023 Fellowship Grant Recipient
Dana-Farber Cancer Institute

Remodeling Lipid Metabolism for Therapeutic Differentiation of H3K27M DIPG

Mentor: Nika Danial

Joana
Joana Graca Marques
2023 Fellowship Grant Recipient
Dana-Farber Cancer Institute

Exploring H3K27ac Deregulation as Therapeutically Actionable in Histone Mutant Pediatric DIPG

Mentor: Mariella Filbin

ErikPeterson
Erik Peterson
2023 Fellowship Grant Recipient
Regents of the University of Michigan

Determining the Effect of ONC201 on DIPG Cellular Metabolism and Targeting Mechanisms of Resistance

Mentor: Daniel Wahl

David Spencer Rogawski
David Rogawski
2023 Fellowship Grant Recipient
Stanford University

Neurophysiological Small Molecule Screen for Inhibitors of Neuron-to-DIPG Communication

Mentor: Michelle Monje

Stefanie-Grace Sbergio 2
Stefanie-Grace Sbergio
2023 Fellowship Grant Recipient
The Hospital for Sick Children

Tumor-Targeted pan-RAS Inhibition as a Novel Therapy for Diffuse Intrinsic Pontine Glioma (DIPG)

Montor: Cynthia Hawkins

Theophilos Tzaridis USE
Theophilos Tzaridis
2023 Fellowship Grant Recipient
Sanford Burnham Prebys Medical Discovery Institute

CD155 as a Novel Regulator of Cell Growth and Immune Evasion in DIPG

Mentor: Robert Wechsler-Reya

Group from DMG Act
DMG-ACT
3rd Year Funding

DMG-ACT Trial

Co-funded by Elle’s Angels Foundation
In addition to the grants made through the structured program, the foundation is excited to continue to support the promising Diffuse Midline Glioma – Adaptive Combinatorial Therapy (DMG-ACT) trial.  The DMG-ACT, a collaboration through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and the DIPG Centre of Expertise in Zurich, is a biology-informed, adaptive, and progressive trial, designed to deliver more rapid progress for children suffering from DMG. Learn more about our funding for the DMG-ACT visit our story HERE.
john_prensner headshot
John Prensner
DDRFA Collaboration Grant Recipient
University of Michigan

Deciphering Aberrant RNA Translation in DIPG

This grant enables the purchase a Beckman-Coulter Optima MAX-XP Tabletop Ultracentrifuge. It is required for the optimized protocol for ribosome profiling for DIPG samples. 

Most DIPGs are triggered by a specific genetic event that impacts the way brain cells regulate DNA activity. In effect, DIPG cells begin to awaken parts of the genome that are generally kept quiescent. Some of these genomic regions may produce retroviral elements. Under normal circumstances, these retroviral elements can be toxic when highly active, but DIPG cells appear to utilize, or at least tolerate, the presence of retroviral elements. Understanding which of these genomic elements are specifically activated in DIPG, and which produce proteins, may provide unique insights into how DIPG cells function, leading to opportunities for novel therapeutic approaches in this deadly childhood brain cancer.

Richard Lu, Cincinnati Children's Hospital Medical Center
Richard Lu
2022 Game Changer Grant
Cincinnati Children's Hospital Medical Center

Targeting Diffuse Midline Gliomas with Rational Combination Therapy

Dr. Lu discovered that chaetocin, a substance produced naturally by a fungus, when combined with radiation, has an impressive killing effect on DMG/DIPG cells. This project will test this combination in conjunction with the oral drug ONC201 to discover why they work so well together and what may be needed to make them even more effective in the future.

Mark Souweidane, Weill Medical College of Cornell University
Mark Souweidane
2022 Game Changer Grant
Weill Medical College of Cornell University

Development of a Comprehensive Direct Drug Delivery Platform for the Treatment of Diffuse Midline Glioma

The objective of Dr. Souweidane’s project is to develop more effective drug delivery methods for DIPG/DMG patients. To accomplish this, he will test various drug combinations and drug delivery techniques to more effectively target DIPG/DMG tumors, while avoiding the toxicities associated with the conventional administration of drug therapies. Dr. Souweidane expects the establishment of this drug-delivery platform will support many cutting-edge therapies and early-stage trials in the fight against DIPG/DMG tumors.

Praveen Raju and Oren Becher
Praveen Raju and Oren Becher
2022 Game Changer Grant
Icahn School of Medicine at Mount Sinai

A clinically translatable nanotherapeutic approach to enhance BBB drug delivery in DIPG

Delivering therapeutics directly to brain tumors safely and effectively has been one of the main limitations for the treatment of DIPG/DMG tumors. Drs. Raju and Becher have recently developed an innovative drug delivery technology that crosses the blood-brain barrier, delivering the drug safely to the site of the tumor. In this study, they will optimize the use of this technology in an effort to improve outcomes for DIPG/DMG patients.

Zachary Reitman
Zachary Reitman
2022 New Investigator Grant
Duke University

Dissecting mechanisms of radio resistance associated with p53 mutations in DIPG

A potential new treatment approach in the fight against DIPG/DMG tumors is to combine radiation therapy with targeted treatments against a specific molecule found in the tumor. However, some subtypes of DIPG appear to be resistant to this method. In this project, Dr. Reitman will carry out experiments to determine why that is so and identify combinations of treatments that could be used to overcome this resistance.

Humsa Venkatesh
Humsa Venkatesh
2022 New Investigator Grant
Brigham and Women's Hospital

Targeting the electrical vulnerabilities of DIPG by modulating the neuronal microenvironment

While the nature of mutations in DIPG/DIPG progression is still not fully understood, nerve cell activity is emerging as a critical cause of tumor growth. In this study, Dr. Venkatesh will use molecular biology and neuroscience techniques to better understand the dynamics between neurons and DIPG cells, along with combination treatment strategies to potentially change the way DIPG/DMG tumors are treated.

Jamie Anastas
Jamie Anastas
2022 New Investigator Grant
Baylor College of Medicine

Combinatorial targeting of Cyclin-Dependent Kinases in DIPG

The objective of this study will be to evaluate the use of drugs that target signaling molecules called CDK. These findings will establish a basis for future clinical trials using these inhibitors as therapies for DIPG/DMG tumors in combination with other drugs. The approach of combining multiple drugs under investigation in clinical trials for DIPG treatment will challenge existing paradigms and provide a basis for the development of drug combinations aimed at achieving complete tumor control.

Orazio Vittorio
Orazio Vittorio
2022 New Investigator Grant
University of New South Wales

Exploring copper chelation as a novel epigenetic therapeutic strategy for DIPG

Dr. Vittorio works with copper chelating agents, which already have wide use in other cancers, to demonstrate the effectiveness of treating brain tumors. This grant will allow his research team to exhibit their expertise in copper biology as they uncover effective drug combinations to reduce copper in DIPG/DMG cancer cells, killing them and improving the survival rate in DIPG/DMG patients.

Michelle Monje
Michelle Monje
2022 Special Project Grant
Stanford University

Car T-cell Trial

Co-funded by Storm the Heavens Fund, the SoSo Strong Pediatric Brain Tumor Foundation & the Elle’s Angels Foundation

In addition to the grants made through the structured program, the foundation is excited to continue to support the promising Car T-cell trial led by Dr. Michelle Monje of Stanford University with our new co-funders, Storm the Heavens Fund, the SoSo Strong Pediatric Brain Tumor Foundation and the Elle’s Angels Foundation.  The trial has shown great promise and, after decades, could finally offer patients with DIPG/DMG a new treatment option for a disease that has historically proven resistant to other therapies.