“The New Investigator Award, granted by the ChadTough Defeat DIPG Foundation, is helping me to find out why some pediatric brain tumors are resistant to radiation therapy and other treatments. This work will help design new treatments that overcome this resistance and improve outcomes for patients with DIPG.” — Dr. Zach Reitman
ChadTough research grants encourage brilliant researchers to focus on DIPG/DMG through our Fellowship Grants for pre-doctoral and post-doctoral candidates and our New Investigator Grants for newly independent DIPG/DMG researchers. Dr. Zach Reitman is the first to receive three grants from our grant program. Dr. Reitman was first awarded a Fellowship Grant in 2017. He has remained committed to his work on DIPG and has since been awarded New Investigator Grants in both 2019 and 2022.
During his fellowship, Dr. Reitman found that a specific gene found in diffuse midline gliomas, called PPM1D, drives DIPG formation early on. This discovery illuminated the idea that these tumors have a unique biological makeup, and therefore a one-size-fits-all approach for DIPG patients was not likely going to lead to a cure. This information has been crucial in the development of the next generation of DIPG clinical trials.
In a recent interview with Dr. Reitman, we learned about his most recent work and how receiving the Fellowship Grant helped shape his career, turning him into a leader in DIPG research.
CTDDF: Can you tell us a bit about yourself and how you decided to work in the world of cancer research?
ZACH REITMAN: I was always interested in biology, even in elementary school. When I was 17, my father was diagnosed with multiple myeloma, a type of blood cancer, and I grew very interested in cancer research. I went to Schreyer Honors College at Penn State for my undergraduate and immersed myself in a biochemistry research lab. My father passed away while I was at college, and the experience spurred me to pursue my MD/PhD at Duke for medical school and research training in cancer research.
CTDDF: At what point in your education did brain tumor research start to gain your attention?
While I knew I wanted to make a difference in cancer research, blood cancer was a bit too close to home. Duke has a really great brain tumor center, and I knew there was a pressing need to improve outcomes for brain tumor patients.
Since radiation treatment plays such an important role for brain tumor patients, I decided to go to Harvard to train in clinical radiation oncology. While there, I did postdoctoral research in some really great labs at the Dana-Farber/ Boston Children’s Hospital and the Broad Institute that nurtured my interest in brain tumors, in particular DIPG and pediatric brain tumors.
CTDDF: You received both a Fellowship Grant and two New Investigator Grants from the ChadTough Defeat DIPG Foundation. Can you tell me a bit about what you learned from past projects?
ZACH REITMAN: I was fortunate to have been awarded a ChadTough Defeat DIPG Fellowship in 2017-2019, and then a New Investigator award in 2020-2021, and now another New Investigator Award for 2022-2024. I’m so grateful, and it really emphasizes that it can be a long road to gain the training and expertise to establish a world-class DIPG research lab and to build up the infrastructure and staff to be able to do the research.
During my fellowship, I studied a gene called PPM1D in diffuse midline gliomas at the Dana-Farber and Boston Children’s Hospital, with my mentors Mimi Bandopadhayay and Rameen Beroukhim (experts in pediatric brain tumor genomics). We worked with Tim Phoenix of the University of Cincinnati, who is an expert at certain mouse models of DIPG. Additionally, I also had the opportunity to help mentor a really bright Harvard graduate student for this work, Prasidda Khadka. We found that the PPM1D mutations are an important biological switch that drives DIPG formation early on. We learned about the molecular mechanism that makes this happen, and our experiments show that certain treatments may work better for patients with PPM1D-mutated DIPG than patients with other types of DIPG. We published this work in Nature Communications in 2022. This work allowed me to gain a great deal of experience with single-cell genomic technologies, which helped me publish another paper in the same journal in 2019. This information is really important for designing new DIPG clinical trials, so the fellowship allowed me to develop the critical skills needed to study DIPG.
The work from the fellowship also helped me to be recruited to Duke to start my own lab in 2019. However, starting a new lab is quite a long process. I was fortunate to have solid mentors at Duke who helped me establish my own genetically engineered mouse colony to study DIPG.
The first New Investigator Award helped me establish a new mouse model of DIPG and hire some of the first of my staff. We published a recent paper in Cancers in 2022 about the model and the findings. Basically, we found that certain genetic subtypes of DIPG may not respond well to a promising investigational therapy. That’s important because it can help us tell which patients should be considered for which DIPG clinical trials in the future. That paper was the first from my independent lab and established that we can get this type of DIPG research done. It demonstrates that we have the mouse models and the small animal radiation machine workflows in place. This is really key to securing grant funding for the lab and paving the way for bigger and more impactful future research.
CTDDF: The latest New Investigator Grant was for your project entitled, “Dissecting mechanisms of radio resistance associated with p53 mutations in DIPG.” What are you hoping to discover through this work?
Our work so far has shown that ATM inhibitors might be a good treatment for some patients with DIPG and should be tested in clinical trials. But we don’t know why some of the molecular subtypes don’t seem to respond to this strategy. Our work in this project examines the molecular mechanisms of resistance. We use our primary mouse models of DIPG to do this and presented some of our preliminary findings recently at the annual Radiation Research Society meeting in October 2022. The work is ongoing, but we hope this will help inform the next generation of combination therapies to overcome treatment resistance in DIPG.
CTDDF: It sounds like you’ve been able to accomplish some incredible things over the last 5 years. How important do you believe grants from private funders like ChadTough Defeat DIPG are in helping foster leaders in DIPG research?
ZACH REITMAN: The fellowship absolutely inspired me to get involved in DIPG research. When I was recruited to Duke to start a brain tumor research lab, the support from ChadTough Defeat DIPG helped me make DIPG an area of special emphasis in the lab. This type of funding is really critical for making sure top labs study DIPG. This funding is important because I think it will “snowball.” For instance, with the preliminary data I was able to generate through support from ChadTough Defeat DIPG, I was able to obtain career development funding from the National Cancer Institute dedicated to DIPG research. I think if it weren’t for the support of ChadTough Defeat DIPG, less of the federal research focus would be on DIPG.
ChadTough Defeat DIPG Foundation is proud to support Dr. Zach Reitman’s exciting research that has helped bring to light the complexities of DIPG. We believe the work happening in Dr. Reitman’s lab will be key in the development of future clinical trials and look forward to following the evolution of his findings.