In the three years of the ChadTough and Defeat DIPG partnership, we have joined together to fund more than $6.7 million for DIPG research projects.
We are committed to building the most comprehensive grant program for funding DIPG research. To achieve this goal, we offer three types of grants:
- Research: supporting the work of existing DIPG researchers by providing funding for hypothesis-driven research projects. The proposed research must represent an innovative approach to a major challenge in DIPG research. The funded projects must have the potential to lead to groundbreaking discoveries in the field, and transform our understanding of the tumorigenesis process or our ability to treat or detect DIPG.
- New Investigator: funding newly independent DIPG researchers in establishing new DIPG research labs – OR – funding established researchers (who have not previously conducted brain tumor research) to encourage them to start DIPG research.
- Fellowship: designed to encourage outstanding scientists to choose a career involving DIPG research.
CHADTOUGH DEFEAT DIPG RESEARCH GRANTS
“Recombinant Attenuated Poliovirus Immunization Vectors Targeting H3.3(K27M) in DIPG.” In recent years, the Duke University team has developed an immunotherapy treatment that uses a modified form of the poliovirus to treat brain tumors. This treatment has received significant attention, including two segments on 60 Minutes. The Duke team recently began a clinical trial using the poliovirus vaccine in children with high-grade gliomas, but DIPG patients were excluded due to a risk of inflammation. In this study, Dr. Ashley is modifying the poliovirus vaccine so that it can be used to treat DIPG patients.
“Enhancing efficacy of adoptive immunotherapy against DIPG using hematopoietic cells.” This immunotherapy project uses adoptive cell therapy, which involves removing cancer cells from the patient, creating a large number of T cells that can identify and attack the cancer cells, and then infusing those cells back into the body. Dr. Flores is developing an adoptive cell therapy treatment for DIPG that uses both the DIPG cells obtained from a biopsy and also cells from the patient’s bone marrow. She will also administer the blood stem cells with the T cells, which can enhance the T cells’ ability to infiltrate the tumor.
“Targeting Cancer Stem Cells in DIPG.” Dr. Galban’s research has identified a small sub-population of DIPG cancer cells known as stem cells, which contain specific genes to protect them from radiation treatment, which permits them to grow and cause tumor recurrence. These cells exhibit high levels of AKT and are especially sensitive to a drug which targets AKT and MAPK, a pathway often upregulated in resistant tumor cells. In this project, Dr. Galban is targeting the signaling axes in cancer stem cells responsible for protecting them from radiation treatment as a new therapeutic strategy for DIPG. She will use a combination of drugs to inhibit these key targets to sensitize them to radiation therapy and to improve patient time to
“Use of a Long Non-coding RNA (lncRNA) as a Therapeutic Target in DIPG.” Recent research has shown that targeting a new class of molecules called long noncoding RNAs (lncRNAs) may provide a unique opportunity to develop effective treatments for DIPG. Drs. Gupta and Lim have identified several lncRNAs that can be targeted to kill DIPG cells without causing harm to normal brain cells, and that can enhance the efficacy of radiation. In this project, Drs. Gupta and Lim are studying these lncRNAs and expect to obtain the data necessary to advance lncRNA therapy to clinical trials in children with DIPG. They also expect that their results will provide new, fundamental insights into why cancer forms and how we might cure this disease.
“The Tumor Microtube Network in DIPG: Targeting a Possible ‘Achilles Heel’ Required to Defeat DIPG.” A recent study of adult brain tumors showed that the cancer cells connect to each other through thin extensions called “tumor microtubes,” and that these connections help the tumor cells survive and resist treatment. Dr. Monje believes she has uncovered similar microtubes within DIPG tumors. She is investigating the microtubes to determine whether targeting them will make DIPG tumor cells more susceptible to treatment.
CHADTOUGH DEFEAT DIPG NEW INVESTIGATOR GRANTS
“Therapeutic Targeting of Metabolic Vulnerabilities in DIPG” Dr. Agnihotri’s research has identified that DIPG cells have an altered metabolism compared to normal cells, and he has determined that DIPG cells are addicted to specific amino acids, which are the building blocks of protein and required for cells to rapidly grow. In this project, Dr. Agnihotri is testing the effects of restricting a particular amino acid, methionine, in his DIPG models, and he will test novel emerging therapies targeting key proteins overexpressed in DIPG in search of novel and innovative ways of targeting DIPG.
“Characterizing long non-coding RNAs as therapeutic targets in Diffuse Intrinsic Pontine Glioma” Recent research has shown that long non-coding RNAs (lncRNAs) can participate in tumor formation and progression, thus representing a novel target for cancer therapy. Dr. Bandopadhayay has performed whole-genome DNA sequencing of DIPG tumors and discovered that almost 10% of tumors carry a rearrangement involving a specific lncRNA that was previously implicated in cancers. In this project, Dr. Bandopadhayay is examining the role this lncRNA plays to control DIPG growth, and she will use genome-editing technology to identify other lncRNAs that are required for DIPG cells to grow.
“MIC2 inhibition mediated apoptosis in DIPG” Most DIPG patients have mutations in histone genes. Dr. Venkataraman’s research has shown that the histone mutations upregulate the MIC2 gene, which codes for a cell surface protein called CD99. In this project, Dr. Venkataraman is comprehensively evaluating the action of CD99 in DIPG and will establish preclinical data to support the rationale for targeting MIC2 for DIPG therapy.
“Optimal combinatorial targeting of HDAC inhibition and radiation in DIPG” Developing effective treatments for DIPG requires good preclinical models that will allow researchers to test potential treatments in the laboratory. Most of the existing preclinical models were developed from DIPG cells that had already been exposed to radiation and chemotherapy, and therefore are not an ideal model of the disease. In this project, Dr. Vitanza is using DIPG cells obtained through biopsies to establish “treatment-naïve” DIPG models. He will also use these models to test the effectiveness of a new drug before, during, and after radiation to identify the most effective possible combination sequence of the drug and radiation.
CHADTOUGH DEFEAT DIPG FELLOWSHIP GRANTS
“Targeting chromatin regulation to treat DIPG” Dr. Anastas studies how the histone mutation commonly found in DIPG affects how the tumor cells function. After screening 1,300 chromatin regulators, she has identified multiple proteins that are necessary for DIPG cells to proliferate and survive, but are dispensable for normal cell growth. Her research is determining the roles of these proteins in DIPG development. Dr. Anastas’s mentor for this project is Yang Shi.
“Therapeutic Targeting of the Disrupted Metabolic State in DIPG to Induce Ferroptotic Cell Death” Dr. Mbah studies how DIPG cells are sensitive to ferroptosis, an iron-dependent form of cell death. Dr. Mbah is testing whether the disrupted metabolic/redox state sensitizes DIPG to ferroptosis, and she is evaluating the anti-tumor activity of ferroptosis in human patient-derived DIPG tumor models. Dr. Mbah’s mentors for this project are Costas Lyssiotis and Sriram Venneti.
“Prioritizing PPM1D mutations as a target for new DIPG therapies” Dr. Reitman studies the role the PPM1D mutation plays in helping DIPG tumors grow. In this project, he is testing whether targeting the PPM1D gene slows DIPG cell growth to determine whether a PPM1D inhibitor should be developed as a potential treatment for DIPG. Dr. Reitman’s mentors for this project are Rameen Beroukhim and Pratiti Bandopadhayay.
“Dissection of ATRX in Diffuse Intrinsic Pontine Glioma” Dr. Shen is focusing on the ATRX protein and its role in driving DIPG tumor growth. Her hypothesis is that the loss of ATRX works with the histone mutation to promote DIPG growth. She is investigating whether the loss of ATRX impacts the DIPG tumor’s response to radiation. Dr. Shen’s mentor for this project is Oren Becher.