Immunotherapy researchers from across the globe are gathering in Zurich, Switzerland, on August 7-8, 2019, for a first-of-its-kind meeting on the role of immunotherapy in treating DIPG and DMG. The working meeting, sponsored by Michael Mosier Defeat DIPG Foundation and organized by the DIPG Center of Expertise Zurich (DCEz), is a gathering of researchers working together to explore and develop a path forward to apply immunotherapy treatments to DIPG and DMG.

“The invited team represents physicians, scientists, and clinical trialists. We need all three areas of expertise to experiment, validate, and translate the knowledge,” explains Javad Nazarian, PhD, MSC, head of the DIPG Research Institute of DCEz and member of the Defeat DIPG Scientific Advisory Council, “We are hoping that this meeting will be the first of such focused meetings and hope that more like-minded colleagues would join to help in making a difference.” 

Over the past two years, Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation, with their chapters and partner families, have made immunotherapy research initiatives a priority and have awarded $500,000 in Defeat DIPG ChadTough Grants to support promising immunotherapy studies.

“Immune-therapeutic approaches have achieved significant breakthroughs for specific adults cancers as well as leukemia; however, successful implementation of immunotherapy for patients with brain tumors – specifically for children with one of the deadliest tumors referred to as DIPG – remains under active investigation,” says Sabine Mueller, MD, PhD, Head of the Clinical Programme of the DCEz and pediatric neuro-oncologist at University of California – San Francisco, “Leading experts will be gathered in this Think Tank to outline a roadmap how to best move immunotherapy approaches forward in children with brain tumors.”

Dr. Nazarian adds, “The meeting would not have happened without the support of Michael Mosier Defeat DIPG Foundation.  The idea of having such a meeting was born just this Spring and the foundation immediately volunteered to support the meeting.  This is a classic example of foundations helping to push the science forward, because they know how little time these children have.”

DCEz, which is a part of the University Children’s Hospital of Zurich, focuses on finding novel ways of treating of DIPG and DMG by researching different drug delivery pathways, combining multiple drugs into a combined therapy, and marrying the best of medical and scientific knowledge bases. The center is hoping to offer new treatments and treatment options to those suffering from DIPG and DMG.

Keep up with what’s going on at the DIPG/DMG Immunotherapy Meeting on Defeat DIPG’s social media accounts (@DefeatDIPG).

Dr. Anastas, Photo by Robyn Guo.

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation, with our chapters and partner families, have partnered to fund more than $3.3 million in Diffuse Intrinsic Pontine Glioma (DIPG) research grants. Their first round of grants was announced in 2017 and included a fellowship grant awarded to Dr. Jamie Anastas, a research fellow at Harvard University and Boston Children’s Hospital.

Dr. Anastas was awarded a Defeat DIPG ChadTough fellowship grant for her study, “Targeting chromatin regulation to treat DIPG.” The study looks at how the histone mutation commonly found in DIPG affects how the tumor cells function. 

Dr. Anastas spoke with the Defeat DIPG ChadTough team to provide an update:

Q: Can you provide an overview of your project?

Dr. Jamie Anastas: “Sure! I’m currently working as a postdoc in Yang Shi’s lab at Boston Children’s Hospital where we study epigenetics, which is essentially a field where we look for factors that can lead to changes in cellular behaviors and gene expression but don’t involve changes in the DNA sequence. So one of the main things that we’re focused on are proteins called histones, which help to control which genes are turned on and off in both normal cells and tumor cells. Histones are really interesting in the context of DIPG because the majority of DIPG tumors produce a mutant version of one of these histone proteins which can then go on to disrupt gene regulation. I’m studying various pathways that regulate the ability of histones and other factors to control cell behaviors to try to figure out if any of those pathways might be targeted in DIPG. Hopefully we can develop new therapies for DIPG and understand a little bit more about the basic biology of this disease.”

Q: Your project says you screened 1,300 regulators in an effort to narrow it down to see which aided in DIPG survival. Are there any results you can share?

Dr. Jamie Anastas: “We don’t have the final answer yet, but I can speak more generally about the method we’re using to try and narrow down pathways. Like you said, we did a screen for around 1,300 different chromatin factors. To do this, we grew up a bunch of DIPG cells and used a relatively new technology called CRISPR Cas9 where we use a bacterial enzyme to induce cuts or disruptions in the sequence of these genes to block their function. Instead of inhibiting one factor at a time, we used a pooled approach where we were able to look at conditions that disrupt the function of all these genes at once in one big experiment. After getting a list of potential hits from the screen, there have been a lot of validation steps. Although we only did the screen initially in two cell lines, we’ve now expanded to many more patient cell lines through collaboration with Mariella Filbin’s and Todd Golub’s groups. 

“The first thing we were able to do was look for hits that were coming across in a majority of the cell lines. We then had to validate the hits in individual cell lines, ensuring that the tools we were using to disrupt these genes really led to the changes we expected. The gene-targeting libraries we used to do the screen were based on a bioinformatic approach, but we still had to actually look at the cells and make sure that the genes were mutated or that the protein encoded by them was lost. We’ve been able to do that for a subset of the screen hits. Another important thing was to see whether disrupting these genes can also affect the growth of normal cells. While it’s not completely essential that disrupting these genes only kills DIPG cells, it’s of course nice if they’re at least more sensitive. When thinking about eventually developing a drug to one of these pathways, we wouldn’t want it to hurt normal tissues.”

Q: What is the next step in the process after completing a project like this, in the grand scope of DIPG?

Dr. Jamie Anastas: “Ideally, once you’re really confident that a certain pathway is important for DIPG growth — including in mouse models, which is something we’re still working on — we would want to then identify a drug or some other therapeutic intervention that can either directly or indirectly affect that pathway. This might involve repurposing already existing drugs, or, in some cases, it might involve trying to generate entirely new compounds or strategies. I think in the context of DIPG, a lot of the pre-existing drugs just haven’t been effective, so I think we need to be open minded about identifying new targets and hopefully continue to work on ways to activate or inhibit them.”

Q: Can you talk about your professional background and how you got to be here doing the study?

Dr. Jamie Anastas: “I went to graduate school at the University of Washington where I was also working on cancer but not working in epigenetics. I was working on secreted molecules called WNTs that can activate various signaling pathways. Somewhere during that process I got really interested in epigenetics and gene regulation, so I went on to contact various labs so that during my postdoc work I would learn about chromatin and epigenetics and genomics and all of these sort of things. I ended up joining the Shi lab, and, at the time I was interviewing in the lab for the postdoc position, papers finding mutations in histone proteins in DIPG and other tumors had just come out. 

“I remember talking to Yang saying that this was really cool, that we should study this, and we should find a way to understand the epigenetic drivers of this disease. It’s been challenging in some ways because the lab I’m in really focuses on the basic molecular biology of chromatin. It’s not a brain tumor lab. So I’ve been really fortunate to have had lots of support from other researchers, Mariella Filbin in particular who’s a neuro oncologist is closely collaborating with us on various projects, other DIPG groups, like Michelle Monje’s, Nada Jabado’s, Keith Ligon’s and Suzanne Baker’s labs have generously given us cell lines and protocols. I think it’s pretty exciting to have a chance to take this knowledge of molecular biology and biochemistry and do our best to apply it to a really terrible disease and a really challenging problem.”

Q: Do you plan to continue focusing on DIPG once this study is complete?

Dr. Jamie Anastas:  “Long term, I’m certainly interested in exploring other mechanisms driving DIPG tumorigenesis. I have a previous background in signaling, so the obvious next steps now that I’ve screened through these different chromatin factors would be to expand to look at how different systems might regulate DIPG growth – signaling or otherwise. It’s definitely something that I’m interested in, it’s just a matter of having the time and personnel to go through those experiments. From a practical point of view — since I’m doing my postdoc in an epigenetics lab where we’ve got all of the tools and expertise in that area — it makes sense for me to focus on the lab’s strengths for now. 

It is also pretty clear that one drug or one intervention like radiation is probably not going to work in DIPG, so being able to understand how different pathways and processes might interact to drive tumorigenesis might be really key to eventually finding treatments that work. Beyond that, these tumors are, of course, not identical even though the majority of them have mutant histones. There’s a lot of heterogeneity, in terms of differences in genetic mutations and potentially in epigenetic regulation. So we may need to look at a variety of targets or pathways to find treatments that may be tailored to individual patients.”

Q: How will this fellowship allow you to advance your career?

Dr. Jamie Anastas: “This fellowship will help my career by giving me the opportunity to pursue more mechanistic lines of research to determine how chromatin regulators might drive DIPG tumorigenesis, which will allow me to learn and develop methods for studying brain tumors more generally. Hopefully, the skills and knowledge gained while supported by the ChadTough and Defeat DIPG foundations will help me prepare to lead a research group focused on understanding the molecular biology of pediatric brain tumors.”

Dr. David Ashley

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation have partnered to fund more than $3.3 million in Diffuse Intrinsic Pontine Glioma (DIPG) research grants. Their first round of grants was announced in 2017 and included a research grant awarded to Dr. David Ashley, the Director of the Preston Robert Tisch Brain Tumor Center at Duke University.

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. In 2017, the Duke team 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, “Recombinant Attenuated Poliovirus Immunization Vectors Targeting H3.3 K27M in DIPG,” Dr. Ashley works to modify the poliovirus to effectively target the H3.3 K27M mutation in DIPG. This mutation occurs in approximately 80-percent of DIPG tumors.

“The Duke team has been doing groundbreaking work in developing the polio virus for treatment of brain tumors in adults,” said Defeat DIPG co-founder, Mark Mosier. “When we saw the stories on 60 Minutes, we knew that we needed to bring this treatment to DIPG. We are very encouraged by the initial work on this project, and we are excited about the possibility that DIPG patients will receive the polio virus treatment in the future.”

Dr. Ashley spoke with the Defeat DIPG ChadTough team to provide an update on this project:

Q: Can you provide an overview of your research project, specifically the excitement around the polio vaccine and the adjustments you’re working on to make this a possible treatment for DIPG?

Dr. Ashley: “The polio virus, in its original form, is a rapidly replicating virus. It causes a lot of inflammation it is an entero-virus, entering patients through the gastrointestinal tract. Matthias Gromier and his colleagues changed that part of the original virus that caused brain toxicity through taking part of the virus out and exchanging it for part of the common cold virus. So, we were able to maintain the inflammatory parts of it, but take away the parts of it that cause the injury to the brain and spinal cord cells.”

“The other interesting part is that the modified polio virus is able to attack cancer cells almost exclusively. Almost every human cancer cell has the entry receptor on it. This means the virus can get into the cancer cell very easily, replicates like crazy and causes inflammation, causes an immune response, and that’s the basis of the use of the polio virus. With use in adults, and with three children we’ve treated now in a pediatric study, we inject the modified virus directly into the brain tumors of the patients. That does seem to be successful in approximately a quarter to a third of patients in causing long-term responses of disease stability in glioblastoma.

“In thinking about DIPG, there’s a couple of issues. One is the delivery of something into the brain that can cause a lot of inflammation. That’s why we haven’t gone immediately to introducing this modified virus directly into the brain. The other is, DIPG does have this target that we’re hoping to exploit: the H3.3 K27M mutation. So, what we hope we are able to do is exploit the inflammation that’s caused by polio virus and add that bit of the H3.3 K27M mutation into the viral vector — into the virus itself — and use it as an immunization, not unlike the way we give original polio vaccine.

“The reason that we think this might be more effective than just using peptides, that under investigation for this illness, is that the virus is much more inflammatory than peptides by getting into the immune cells and it activating the immune cells. We think it’s really a clever way of administering a vaccine against the H3.3 K27M target in DIPG. That is the basis of this study.”

Q: Will you be injecting this vaccine directly into the tumor?

Dr. Ashley: Rather than using the polio virus for a direct injection into the brain tumor, we’re going to be using the polio virus construct in a vaccination schedule. Ultimately, the patient would get a vaccine just like they would get a polio vaccine — just an injection into the muscle. Then we think there will be immune responses to the virus and in turn to the mutant H3.3 K27M.”

Q: Is this particular mutation present in all DIPGs or only certain mutations of DIPG?

Dr. Ashley: “This is a mutation that’s in the vast majority of DIPG – approximately 80 percent. In fact, outside DIPG, this particular mutation is carried in other high grade tumors in childhood as well. So we would hope that this could be something that could be helpful for the majority of patients with DIPG. So, where to from here? The next step will be to go to the FDA to understand what other evidence or studies they’d like to see before we move toward clinical trial.”

Q: You recently submitted your manuscript for publication – what does that paper include?

Dr. Ashley: “We’ve created the construct, done the work rebuilding the virus, and then we’ve been able to do parallel experiments in mice and in human cells. We used a model system with a protein that we know works to immunize mice against tumors, so we showed that we could use the virus in that situation and get immune effects. Then, in addition to that, we’re able to take human cells and infect them with the human virus and show that we’re able to derive a very robust immune response in human cells … in a dish, if you like. So, we have two levels of evidence that this is going to work. One is in animals and the other is in a dish with human cells.”

Q: Can you articulate how important foundation funding is for research of this type of disease?

Dr. Ashley: “The answer is twofold. One, it’s a very rare disease. Although it’s horrible for families and the patients, obviously, it’s difficult to get funding for these sort of rare diseases, because public health institutions and large organizations tend to focus on the ‘big-ticket items,’ the big public health scourges. Second, it’s really hard to get initial startup funding to do this type of research, because it is pretty innovative and high risk. We didn’t know that this would work. We thought it would, we had hypothesised it would, but before you’ve got preliminary data to support your hypotheses, it’s really hard to get national peer-reviewed funding for this type of work. The funds that the Defeat DIPG and ChadTough Foundations provide allows us to do early, innovative work like this in rare diseases that otherwise would never get done.”

Zach Reitman
Zach Reitman, MD, PhD

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation have partnered to fund more than $3.3 million in Diffuse Intrinsic Pontine Glioma (DIPG) grants. Their first round of grants were announced in 2017 and included a fellowship awarded to Zach Reitman, MD, PhD (Harvard University, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center).

Reitman spoke with Defeat DIPG ChadTough team to provide an update on his project, “Prioritizing PPM1D mutations as a target for new DIPG therapies,” for foundation supporters:

Q: Can you provide an overview of your research project?

A: “Happy to do so. In both the lab I’m working in and around the world, much has recently been learned about the biology of DIPGs through genomic sequencing. This work has revealed what we think drives these tumors to grow inappropriately. I’m focusing on one of the findings of this research, which is that one particular gene called PPM1D is likely to be a key driver of DIPG.

“My project is to find out more about how and why this PPM1D gene drives DIPG tumor growth. We’re growing DIPG tumor cells in a petri dish, and in mice, as laboratory models of DIPG. We’re then using genetic techniques to experiment with the PPM1D gene to find out how PPM1D is driving these model DIPG tumors to grow.

“This is really important because it will give us some clues as to why these deadly brain tumors are forming. I think it will also give us some important information on what the best way is to treat these tumors. For instance, we are finding out whether treatments that affect what the PPM1D gene is doing are likely to be effective treatments for DIPG.”

Q: How did you come across this idea?

A: “It’s really an amazing story. A lot of researchers became interested in looking at the genetics of DIPGs over the past 10 years. One of the reasons this was done is because the technology to sequence the genome and look at the genetics of tumors has dramatically improved over the past several years .

“This inspired several groups to carefully collect tumor tissue from patients with DIPG, and then to apply some of these new genomics technologies to uncover what really makes these DIPGs tick. At the time, I was working in a lab at Duke University. We carried out some genomic analyses of DIPGs, and we found this fascinating change in the PPM1D gene that I’m studying now.

“So this idea all dates back to that finding. One of the neat parts of the story is that several other groups were also looking at the genomics of DIPG patients and found that this same PPM1D gene is mutated in up to a quarter of DIPG patients worldwide. That really built up our confidence that this is really an important piece of the biology of DIPG, and not just something that was unique to the handful of DIPG tumors we had studied. It’s really a remarkable story where new technology came around, led researchers around the world to conduct some bold investigations with the permission of the patients and their families, and it led to paradigm-shifting discoveries.

“I’m now following up one of those discoveries and I’m hopeful this will help identify effective treatments for this deadly tumor.”

Q: One important thing you mentioned is collaboration across different labs and different researchers. Chad Carr’s tumor was sequenced at Michigan and they found PTEN as a key driver. What are your thoughts are around the different mutations of DIPG and the different people studying DIPG across a number of institutions?

A: “It’s so important for different researchers to study DIPG for a few reasons:

“First, I think studying diverse key drivers in DIPG is really important. This is because what we’ve found is that genetically, each DIPG is a little bit different – each patient’s tumor can have a different key driver or drivers. Some tumors, like Chad’s tumor, have PTEN as a key driver. Other tumors might have PPM1D, the gene I’m working on, as a key driver. Some tumors might have both. Others might have neither, or something else. This is why we need different groups to study the different key drivers in DIPG. We need to identify treatments that could work on tumors that have PTEN as a key driver. And we need to identify treatments that could work on patients with PPM1D as a key driver. The same goes for a number of other important drivers in DIPG. That way, when a child is diagnosed with a DIPG, there is going to be a high likelihood that research is being done that could be important for that child’s tumor.

“Second, I think having multiple researchers focusing on DIPG gives us more “shots on goal.” In cancer research, it’s very hard predict which research projects are going to ultimately result in an improvement in the standard of care for patients. In fact, most lines of research don’t ultimately lead to an improvement in how patients do. I think this speaks to the magnitude of the challenge we are up against. But there have been some amazing success stories in other types of cancer. Some types of cancer that were incurable in the past are now curable due to successful research efforts. I think by supporting many diverse ideas on how to improve care for DIPG patients, you maximize the chances that at least one of them will result in a success story for DIPG.

“Third, DIPG is a rare tumor. If only one institution studied it, you’d only have a few patients to glean information from, and you wouldn’t get a very complete picture of the biology of the disease or what treatments are going to work on the majority of DIPG patients. It’s so important to have many different institutions working together on this problem so we can combine our knowledge.”

Q: Can you go over your method and what you’re looking to produce out of your project? The answers you’re hoping to generate?

A: “One of the key methods we’re using is called CRISPR. This is a technique that’s emerged in the past few years in the molecular biology community that lets us edit the genome. A little bit of background: every cell in our body — or every cell in a DIPG tumor — contains approximately three billion pieces of DNA, or letters of DNA. CRISPR lets us very precisely edit a specific letter of that DNA. It’s a game changer.

“The CRISPR technology lets us ask some therapeutically imporatant questions. For instance, it lets us ask if a particular letter of DNA is important for DIPG cells to grow. One of the central aims of my work is to test whether a few important letters in the PPM1D gene are important for the growth of DIPG tumors using CRISPR. We’re using CRISPR to edit this gene and see if that causes the tumor to stop growing. Our hope is to produce a publication describing this, describing what we see, and we think that this will be valuable to determine whether treatments that affect this particular gene are worth pursuing.”

Q: Can you explain what happens after you publish a paper? How does that work in the grand scheme of DIPG?

A: “While our ultimate goal is to identify new treatments for DIPG, publications are an important milestone because they allow us to disseminate new research findings. This benefits the DIPG research community, because it gives other scientists a chance to build on our results. This also gives other groups a chance to validate our work and make sure its reproducible. An important part of the publication process is that the research is peer reviewed by other scientists, who make sure the work is rigorous and provide some feedback that can be very helpful to future work. And we continue to get feedback from the research community after the publication, which can be helpful for ongoing work and could even result in fruitful research collaborations.

“In some cases, publications can provide information for folks in the pharmaceutical industry in order to help them develop the best new cancer therapies. An important piece of background for this project is that pharmaceutical companies have already been developing chemicals that specifically target PPM1D, which is the gene we’re studying. This could eventually lead the way to a drug that targets PPM1D in the clinic. But there’s still a long way to go to get a drug that’s ready for clinical trials in kids. Developing a drug to that point is costly and takes years. A pharmaceutical company has to have a information that indicates that their drug likely to be helpful in order to make the investment to continue to pursue drug development.

“With our project, we hope that we can figure out if a drug that targets PPM1D is likely to be useful in kids with DIPG. If it is, it will provide a rationale that it might be worth the investment to develop a drug further. If we find out this isn’t likely to be a good strategy, it might help guide resources to be allocated towards more promising projects.

“Another interesting finding is that PPM1D also seems to be important in other types of cancers like breast cancer and some gynecologic cancers. So if we can show in our lab that it’s also important in DIPG, we can say, ‘Hey, look, this is a really important drug target. If a drug is developed that hits this target, it might be helpful for kids with DIPG in addition to these other tumor types. We’re hoping to provide a really fundamental biological insight that could prioritize whether this way of treating these tumors should be pursued further.”

Q: How will the Defeat DIPG ChadTough Fellowship impact your career?

A: “As I carry out this research project, the Defeat DIPG ChadTough Fellowship is providing me with research training that will help me in my career goal of establishing a laboratory aimed at identifying new treatment strategies for tumors like DIPG. As I mentioned above, I think work by multiple independent research groups is critical for the overall success of DIPG research. Training the next generation of research leaders is important to maintain this research community, and make sure that the very best people are going into DIPG research.

“A diverse set of skills is needed to lead a team that can tackle a terrible disease like DIPG. These skills do include a deep understanding of experimental laboratory techniques. But they also include skills to manage a team of researchers, to plan out long-term research projects, to understand how findings in the laboratory are translated to the clinic, and to effectively communicate results. And one needs experience in managing a budget to make sure funds are spent appropriately and effectively.

“Mastering these skills doesn’t happen overnight. For me, it started with my MD and PhD degrees at Duke University, which I followed with clinical residency training in the Harvard Radiation Oncology Program. The Defeat DIPG ChadTough fellowship is now giving me a chance to further master laboratory skills, to supervise a small group of researchers, and to start managing research funds. This is all being done under the supervision of my research mentors, Dr. Pratiti Bandopadhayay and Dr. Rameen Beroukhim, who both have a successful track record of leading research teams at the Dana-Farber Cancer Institute. By enabling me to gain this experience and to successfully complete meaningful projects, the fellowship is helping me towards my goal of one day leading a research group and identifying new treatment strategies for DIPG.”

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation are excited to have Zach Reitman engaged in this research project, uncovering important data for DIPG research. Both foundations look forward to what he will do in the field in the future.

Zach Reitman with members of his lab, Adam Boynton and Prasidda Khadka.

Mark and Jenny Mosier and Tammi and Jason Carr

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation are funding seven new Diffuse Intrinsic Pontine Glioma (DIPG)-specific research projects totaling more than $2.2 million over the next three years (2019-21). To date, the Defeat DIPG ChadTough partnership has committed $3.3 million to 13 DIPG research projects, ranging in focus from immunotherapy to fundamental biology of DIPG to epigenetics.

“To see that number – that we’ve come together to give $3.3 million to DIPG-specific research – is incredible,” said Tammi Carr, co-founder of The ChadTough Foundation. “Family foundations are the driving force behind finding a cure for this monster, so to be able to award this much over the past two years is an amazing feeling.”

The seven projects to be funded include: two research grants ($600,000 over three years), one fellowship ($150,000 over two years), and four new investigator grants ($250,000 over two years), which are new to this year’s Defeat DIPG ChadTough grantmaking cycle.

“A big part of our funding strategy is to increase the number of researchers dedicating their focus to DIPG,” said Defeat DIPG co-founder Mark Mosier. “New investigator grants are directed toward individuals in their first independent faculty position or those who have never researched brain tumors, which means we’re reaching a new group of scientists.”

Another important part of their strategy was to make longer-term commitments to funding the researchers awarded grants. All of the Defeat DIPG ChadTough grants are multi-year grants, allowing researchers to spend more of their time in the lab and less seeking additional funding for future years.

“As families that have been through the devastation of this disease, we recognize the urgency for answers,” said Jason Carr, co-founder of The ChadTough Foundation. “We put our grant application in front of as many talented researchers as we could, and structured our grants to set them up for success.”

All projects are reviewed by the Defeat DIPG Scientific Advisory Council made up of Darell Bigner (Duke University School of Medicine), Suzanne Baker (St. Jude Children’s Research Hospital), Oren Becher (Northwestern University’s Feinberg School of Medicine), Cynthia Hawkins (Hospital for Sick Children), Duane Mitchell (University of Florida College of Medicine), Michelle Monje (Stanford University), and Javad Nazarian (Children’s National Medical Center).

The Defeat DIPG ChadTough partnership was announced in 2017 with the funding of six projects (three research grants, three fellowships), totaling over $1 million over two years (2018-19). The Carr and Mosier families originally connected in the months following their sons being diagnosed with DIPG in September 2014. They quickly uncovered their shared passion for honoring their sons through raising research dollars.

Defeat DIPG ChadTough Partnership

(Top, L-R): Chad, Michael, Connor; (Middle, L-R): Tommy, Vivian, Avery; (Bottom, L-R): Julian, Anthony, Addison

Defeat DIPG and ChadTough bring together nine families with children who have fought or are fighting DIPG that are actively raising research dollars:

The ChadTough Foundation is led by co-founders Jason and Tammi Carr (Chad), and includes partner families Brad and Nettie Boivin (Team Julian), and Tom and Amanda Ruddy (Team Tommy).

Michael Mosier Defeat DIPG Foundation is led by co-founders Mark and Jenny Mosier, and includes their Defeat DIPG Network chapters: Addison Grace Defeat DIPG Foundation (PA), Anthony’s Avengers Defeat DIPG Foundation (IL), Avery Huffman Defeat DIPG Foundation (WA), Connor Man Defeat DIPG Foundation (TX), and Vivian Rose Weaver Defeat DIPG Foundation (WA).

“Each family has channeled their grief into raising money for research,” said Jenny Mosier, Executive Director of Michael Mosier Defeat DIPG Foundation. “While nothing will erase the loss we feel, standing together to make tangible progress in this fight is one thing that keeps us going.”

Learn more about The ChadTough Foundation at and Michael Mosier Defeat DIPG Foundation at

Research Grants

  • Stefanie Galban, University of Michigan, “Targeting Cancer Stem cells in Diffuse Intrinsic Pontine Glioma (DIPG).
  • Nalin Gupta and Daniel Lim, University of California San Francisco, “Use of Long Non-coding RNA (IncRNA) as a Therapeutic Target in DIPG”

New Investigator Grants

  • Sameer Agnihotri, University of Pittsburgh, “Therapeutic Targeting of Metabolic Vulnerabilities in DIPG”
  • Pratiti Bandopadhayay, Dana-Farber Cancer Institute, “Characterizing long non-coding RNAs as therapeutic targets in DIPG”
  • Sujatha Venkataraman, University of Colorado-Denver, “MIC2 inhibition mediated apoptosis in DIPG”
  • Nicholas Vitanza, Fred Hutchinson Cancer Research Center, “Optimal combinatorial targeting of HDAC inhibition and radiation in DIPG”


  • Nneka Mbah, University of Michigan, “Therapeutic Targeting of the Disrupted Metabolic State in DIPG to Induce Ferroptotic Cell Death”

Vivian Rose Weaver Defeat DIPG Foundation, in Husum, WA, is excited to announce that a generous anonymous supporter has donated $1 million that will be used towards DIPG-specific research funding in 2018. Vivian Rose Weaver Defeat DIPG Foundation was inspired by, and established in honor of, Vivian Rose Weaver, who is a smart, articulate, funny, sweet, thoughtful, imaginative, precocious, 3.5-year-old little girl who was diagnosed in February 2018 with a brainstem tumor called diffuse intrinsic pontine glioma (DIPG). DIPG is the deadliest form of pediatric brain cancer.  Vivian Rose Weaver Defeat DIPG Foundation is a chapter of Michael Mosier Defeat DIPG Foundation and part of Defeat DIPG Network.

Co-Founders Katie and Simon Weaver are focusing on Vivian’s care, and her little sister Lucie, as their top priority.  But they are also already making a substantial impact on the field of DIPG research by raising crucial funds to find a cure.

And the Weavers are not stopping with $1 million.

Vivian Rose Defeat DIPG Foundation would like to raise an additional $1 million this year, with an overall 2018 goal of $2 million raised for research.  To put these numbers in perspective, the overall funding for DIPG research in any given year has typically been – at most – $2-5 million in a year.  This is .0005% of the total funding for cancer research.

The funds raised will support the most promising DIPG research initiatives through the Defeat DIPG grantmaking process.  All grant applications go through a rigorous review by a preeminent group of brain tumor experts that serve on the Defeat DIPG Scientific Advisory Council to ensure funds are used efficiently for initiatives with high scientific merit.

We call on everyone to join this effort.  And, it couldn’t be easier.

An initiative called the #LemonFaceChallenge, started by a little girl named Aubreigh who is also fighting DIPG, has triggered worldwide attention to DIPG brain tumors.  It has been heartening to see professional sports teams and coaches, members of the media, and so many others participate. The challenge is in the mold of the Ice Bucket Challenge, which raised $115 million in the summer of 2014 for ALS (amyotrophic lateral sclerosis or Lou Gehrig’s disease), dramatically increasing available funds for research for that disease.

Vivian Weaver, who inspired the $1 million donation to DIPG research, along with her parents Simon and Katie, are asking you to help us generate even more funds to find a cure.  Vivian and the Weaver family are taking #LemonFaceChallenge and calling on you to keep the challenge going.

Here’s what you do:

  1. Take a video of yourself, your kids, your friends, your co-workers – anyone you can who will participate in the #LemonFaceChallenge, which means you take a big bite out of a lemon wedge!
  2. Tell them you are donating to Defeat DIPG and doing the video to find a cure for children facing DIPG, the deadliest form of pediatric brain cancer.
  3. Share the video and tag as many friends as you can and ask them to take the challenge.
  4. Donate to Vivian Rose Defeat DIPG Foundation through the Facebook fundraiser pinned to the top of their Facebook page (which has no processing fees), through their website, or through any member of Defeat DIPG Network.

DIPG is the deadliest form of pediatric brain cancer, with a median survival from diagnosis of 9 months and a near 0% survival overall. DIPG typically strikes children between ages four and eleven. Because of its location in the brainstem where all motor activity is controlled, DIPG is inoperable. The disease progresses by taking over a child’s motor functions one-by-one, typically starting with vision and balance problems, before moving to partial paralysis, followed by the inability to chew, speak, swallow, move and eventually breathe – all of this while the child remains mentally intact.

Raising $2 million through this initiative is a lofty goal.  But, if kids like Vivian can fight hard every single day to beat this brain tumor, we can fight just as hard to make sure there are effective treatments for kids like her.

By supporting Defeat DIPG Network, you have the opportunity to move the needle and help us save lives of our precious children.  Together, we will substantially increase research funding while also greatly increasing awareness of this devastating disease.

Michael Mosier Defeat DIPG® Foundation, a nonprofit whose mission is finding a cure for the deadliest pediatric brain cancer, DIPG (diffuse intrinsic pontine glioma), announced today the addition of a second chapter in Washington State, to its Defeat DIPG® Network:  Vivian Rose Weaver Defeat DIPG® Foundation.  Vivian Rose Weaver Defeat DIPG Foundation is founded in honor of Vivian Rose Weaver, a 3.5-year-old girl from Husum, Washington, who has been battling a DIPG brain tumor for nearly 3 months.

The new chapter adds to Defeat DIPG Network’s existing presence across the United States, in Maryland, Washington, D.C., and Kansas as Michael Mosier Defeat DIPG Foundation, in Illinois as Anthony’s Avengers Defeat DIPG® Foundation, in Pennsylvania as Addison Grace Defeat DIPG® Foundation, in Texas as Connor Man Defeat DIPG® Foundation and in Washington as Avery Huffman Defeat DIPG® Foundation. The Defeat DIPG Network has raised over $2 million for DIPG research in 2.5 years.

Vivian Rose Weaver was diagnosed with a brainstem tumor on February 1, 2018. With great bravery, 3-year-oldVivian has faced a number of difficult medical procedures over the past few months, including a biopsy and 30 rounds of radiation treatment that required daily sedation. Vivian’s family describes her as a smart, articulate, funny, sweet, thoughtful imaginative, and precocious little girl who is full of love for life and people.  Fortunately, Vivian has been doing well and is virtually symptom free.

“Learning that our little girl has DIPG was devastating – a worst case scenario,” says Vivian’s mother Katie Weaver, who will serve as the Director of Vivian Rose Weaver Defeat DIPG Foundation. “We are launching a multi-pronged attack on this disease, through our prayers for God’s healing, by finding the most promising treatments we can for Vivian, and now through our efforts to raise fund for essential research for a cure.”

Jenny and Mark Mosier created Michael Mosier Defeat DIPG Foundation in June 2015 to fund DIPG research and promote awareness of the disease, after the passing of their 6-year-old son Michael. With its geographic expansion and growth of existing initiatives, the Foundation expects to continue to increase its capacity to fund essential childhood cancer research.

In December 2017, the Foundation announced over $1 million in DIPG-specific research funding, in partnership with The ChadTough Foundation. Michael Mosier Defeat DIPG Foundation works with a preeminent Scientific Advisory Council of brain tumor experts that advises its Board of Directors on how to maximize its resources to fund research for a cure for DIPG. The Foundation will soon begin accepting grant applications for 2018, and expects to announce another round of funding before the end of 2018.

The Mosier, Gaskin, Holl, Huffman, Olympia, and Weaver families will work to grow the already powerful base of support in each of their communities, and to honor and unite all children and families who have had to confront this disease.

“Joining together with the Weaver family – who are in the midst of the difficult fight against this disease with their precious daughter Vivian – even further motivates our efforts and our urgency to find a cure for DIPG,” says Jenny Mosier, Executive Director of Michael Mosier Defeat DIPG Foundation. “After experiencing firsthand the cruel impact DIPG inflicted on our own children, we are laser focused on our mission to eradicate this disease.”

DIPG is the deadliest form of pediatric brain cancer, with a median survival from diagnosis of 9 months and a near 0% survival overall. DIPG typically strikes children between ages four and eleven. Because of its location in the brainstem where all motor activity is controlled, DIPG is inoperable. The disease progresses by taking over a child’s motor functions one-by-one, typically starting with vision and balance problems, before moving to partial paralysis, followed by the inability to chew, speak, swallow, move and eventually breathe – all of this while the child remains mentally intact.

For decades, treatment for DIPG has remained the same and has been ineffective. The entire amount spent annually on DIPG research – approximately $3 – 5 million – is less than 0.0005% of the total funding for cancer research.  In just the past few years, due to better medical technology and increased access to tumor tissue, researchers have made real advances in their understanding of this disease.  There is finally hope for progress in finding a cure.

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