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. The first round of grants was announced in 2017 and included a fellowship grant awarded to Dr. Chen Shen, a research fellow at Northwestern University. Her study is entitled “Dissection of ATRX in Diffuse Intrinsic Pontine Glioma.”
Defeat DIPG ChadTough Fellowship grants are designed to encourage outstanding scientists to choose a career involving DIPG research.
“This fellowship provides me an opportunity to work on an area that few people focus on, and the passion of the families like the Carrs and Mosiers keeps me motivated every day to try to find a cure,” shares Dr. Shen.
Under the direction of Dr. Oren Becher at Northwestern University Feinberg School of Medicine, Dr. Shen’s project focuses on the ATRX protein and its role in driving DIPG tumor growth. Dr. Becher’s laboratory is unique because they study DIPG exclusively and do so through genetically engineered mouse models. Because DIPG is a heterogeneous disease, they can develop mouse models to control for specific mutations to understand how each mutation may contribute to DIPG.
The first step of Dr. Shen’s project was to develop a new mouse model that also deleted ATRX in addition to the histone mutation to study how ATRX contributes to DIPG formation. While the histone mutation is commonly seen in human DIPG tumors, ATRX has been found to be deleted in a subset of only 10-30% of human DIPG tumors. When ATRX deletions do occur in human DIPG tumors, they co-occur with the more commonly seen histone mutations. This model will be used to look at what happens when you add the deletion of ATRX on top of the histone mutation.
Dr. Becher reports that the new mouse model has been developed and work is ongoing to evaluate how ATRX deletion changes genes that are turned on in tumor cells. Final results are expected at the end of this year.
Interestingly, they were also able to obtain additional information on some other genes that appear to be regulated by ATRX loss with this model, and are currently validating these genes that are differentially expressed between the tumors with and without ATRX. “Once we validate these genes that appear to be regulated by ATRX, this will be important knowledge for the field because it has not been well described what genes are regulated by ATRX in DIPG cells specifically with the histone mutation,” said Dr. Becher.
Additionally, Dr. Shen will test some of the ATRX mutant mouse cell lines with and without ATRX loss to see how ATRX affects response to radiation. Radiation is the current standard of treatment for DIPG used to temporarily improve clinical symptoms, and can increase survival by about 3-6 months. Dr. Becher notes that not all children with DIPG respond to radiation in the same way. “There are some kids that we treat with radiation and they don’t benefit at all and some that have a dramatic response,” said Dr. Becher. Because of these differences in response, they would like to explore if this response can be linked to ATRX loss.
Dr. Becher’s lab will continue this project after the fellowship grant work ends as they have some new angles to explore once the target genes that appear to be regulated by ATRX have been validated. This work is planned to begin soon.
–Written by Ellen Klepack, a ChadTough Volunteer Writer
https://www.defeatdipg.org/wp-content/uploads/2019/10/image0.jpeg18001200Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-10-31 15:45:032019-10-31 15:51:46Northwestern University’s Dr. Chen Shen Studies How ATRX Mutation Affects DIPG
The 3rd Annual Defeat DIPG Dream Big Gala, presented by DARCARS Automotive Group was held on Saturday, October 26. Thanks to our sponsors, attendees and other supporters, we are thrilled to report that we raised over $470,000! We are deeply grateful to all of our sponsors who stand with us in this fight and supported this important event.
This year’s Michael Mosier Big Hero Award honoree and keynote speaker was world-renowned author Mitch Albom. Mitch gave a riveting speech about Chika Jeune, the beautiful little girl who he and his wife Janine brought into their home and family from an orphanage in Haiti, during Chika’s battle with DIPG. It was a privilege to get to know more about Chika through Mitch’s loving words. Through the stories he shared and videos of Chika, her incredible spirit shines through and touched all of our hearts. Mitch’s new book, Finding Chika, will be released on November 5.
Each year, we present the Michael Mosier Big Hero Award to a recipient who has made an extraordinary commitment to Defeat DIPG. The care and compassion that Mitch and Janine showed to their beloved Chika is a beautiful act in and of itself. And the gift of sharing her story with the world through Finding Chika will not only ensure that Chika is always remembered, but also educate millions about the impact of DIPG and the devastating struggle that all children with this disease have endured.
Dreaming Big is dreaming of a cure for DIPG brain tumors. These funds will be put into action to make sure we are pushing forward our mission to Defeat DIPG.
It was our biggest gala yet, with over 500 tickets sold, and you could feel the strength and determination of our crowd. Progress will happen because we work together. Strides will be made because so many who haven’t been personally touched by DIPG decide to take up the cause as their own.
For those families who unfortunately are part of the DIPG club, we thank you for standing with us and allowing us to honor your children. It was especially meaningful to have so many of you there in person, especially when we know that the emotions of the night are so hard on your hearts.
To each person who joined us, sponsored DIPG family tickets, donated or bought auction items, and otherwise contributed to our mission, THANK YOU.
This year’s gala ended up on Game 4 of the World Series, with a game at home for Michael’s beloved Nationals. Michael dreamed of becoming a professional baseball player, and it was somehow fitting that the gala overlapped with D.C.’s first World Series since 1933. We continue this fight so that kids like Michael can carry out their dreams.
We Dream Big. And, these kids deserve nothing less. Together, we will Defeat DIPG.
https://www.defeatdipg.org/wp-content/uploads/2019/10/MHC_0457.jpg40006000Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-10-29 13:33:132019-10-31 15:23:073rd Annual Defeat DIPG Dream Big Gala Raises Over $470,000
Immunotherapy researchers from across the globe gathered 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), was a gathering of researchers working together to explore and develop a path forward to apply immunotherapy treatments to DIPG and DMG.
“The invited team represented 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, “This meeting was the first of such focused meetings and we hope that more like-minded colleagues will 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 and supported with funds by the Eliminate Cancer Initiative, 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).
https://www.defeatdipg.org/wp-content/uploads/2019/07/skyline-over-zurich-switzerland_800.jpg533800Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-07-31 11:16:452019-08-26 10:57:47Immunotherapy Experts Gather to Tackle DIPG
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 […]
https://www.defeatdipg.org/wp-content/uploads/2019/06/image002.jpg37355309Chrissie Wywrothttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngChrissie Wywrot2019-06-28 09:18:182019-06-29 10:27:11Harvard's Dr. Anastas: Applying Epigenetics to Unlock the Mystery of DIPG Growth
On June 20, 2019, Jenny Mosier, Executive Director of Michael Mosier Defeat DIPG Foundation, gave a presentation to the Food and Drug Administration (FDA) regarding development of ONC201 as a potential therapy for DIPG patients. In her remarks, Mosier urged the FDA (1) to include DIPG patients in the development of ONC201, (2) to utilize all tools available to expedite development and approval of ONC201 for DIPG, and (3) while ONC201 continues to be studied, to take steps within the trial or through expanded access to enable as many patients as possible to gain access to the drug.
The public hearing was held by the FDA’s Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee, to gauge investigator interest in exploring potential pediatric development plans for ONC201, including discussion of diseases to be studied, patient populations to be included, and possible study designs in the development of this product for pediatric use.
Oncoceutics, Inc., the company developing ONC201 presented its early findings and plans for development of ONC201. Two current DIPG families gave passionate and moving presentations about their experience taking ONC201. Al Musella of The Musella Foundation also advocated for prompt action to move forward ONC201 development and approval.
Michael Mosier Defeat DIPG Foundation has made grants of over $166,000 in support of development of ONC201 and to help increase availablilty of ONC201 for DIPG patients, including through Oncoceutics’ expanded access program.
You can view written materials available from the meeting on the FDA website. FDA provided a live webcast of the meeting, and they plan to post the archived webcast after the meeting conclusion. It should appear here once available.
https://www.defeatdipg.org/wp-content/uploads/2019/06/si-FDA.jpg393699Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-06-20 15:30:072019-06-20 16:54:00Defeat DIPG Executive Director Jenny Mosier Speaks at FDA Public Hearing Regarding ONC201
The 4th Annual Defeat DIPG Superhero Sprint & 6K was the biggest yet, raising over $245,000 (and counting) with an incredible 2,400 participants. This included 1,800 people registered for the in-person event on the grounds of our Community Partner Westfield Montgomery in Bethesda, and 600 virtual runners supporting the event across the world!
We want to especially thank our special superheroes who joined us at the race: Delaney Heller, Jack Overton, Maddie Hartman, and Mikeal Richardson. We were so thankful to have them with us, and we stand with them as they fight so bravely against DIPG. We also send love to Libby Goodwin who was unable to make it but had her father and sisters representing her at the event.
Special congratulations to all of our Top Race Finishers. Scott Anderson of Washington, DC was the 1st place male open finisher and #1 overall with a time of 22:13. Rachel Greszler of Bethesda, MD was our top female open finisher with a time of 25:46. Thank you to Urban Plates for donating gift card prizes for the top male open, female open, and masters runners.
Our top fundraising team for the event was the amazing MIRAH’S MANY, created in memory of and inspired by sweet Mirah Chhabra, who passed away from DIPG in December 2018. Her parents, Mandeep and Hanita, and sister, Hanna, led their team to raise over $48,000, with over 700 runners registered. We thank all members of Mirah’s Many who helped with this incredible contribution to the mission to Defeat DIPG. Our top individual fundraiser for the event was a member of Mirah’s Many, Zachary Zimmerman, who raised over $1,600.
Together, all participants who have fundraised for this event generated over $121,000 and counting.
We thank Tommy McFly from The Tommy Show! and NBC4Washington for his time, energy and passion for the cause; DJ Jamaal for the awesome tunes that kept us all having fun yesterday; and Joanna Little Photography and Yee-Ann Soong for capturing event photos (which we will share soon!); Quiet Sweep for generous assistance with race cleanup; Elizabeth O’Connor, Jen Davis, and Gina Spallina for their work on the Salute Our Superheroes Wall; and Alex and Ari Reichmann from Rock Creek Velo for doing a great job as our bike leads.
We had a stellar group of volunteers that worked incredibly hard and made this event possible. We thank the excellent event staff from Montgomery County Road Runners for their expert assistance on race day. We thank the management and secuirty teams at Westfield Montgomery for their invaluable support. And, we are grateful to the spectators that made key contributions to the fun and festive atmosphere.
We are so grateful for each and every one of you. Thank you for your support for our event and the fight to Defeat DIPG!
https://www.defeatdipg.org/wp-content/uploads/2019/04/IMG_5653.jpg720535Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-04-12 06:00:172019-04-11 20:29:43Announcing New Kansas Chapter: Carson Hall Defeat DIPG Foundation
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.”
https://www.defeatdipg.org/wp-content/uploads/2019/03/David-Ashley1-235x300.jpg300235Chrissie Wywrothttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngChrissie Wywrot2019-04-09 10:53:542019-04-10 15:32:06Polio as a treatment? Dr. Ashley thinks it’s possible.
https://www.defeatdipg.org/wp-content/uploads/2019/03/ONC201-284x300-2.png300284Jenny Mosierhttps://www.defeatdipg.org/wp-content/uploads/2018/03/DefeatDIPG-Logo-216.pngJenny Mosier2019-03-12 16:38:232019-04-10 15:36:36xCures to Implement an Intermediate Size Expanded Access Protocol for ONC201
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.