In the fight against childhood brain cancer the Children’s Brain Tumor Network prioritizes radical transparency and collaboration at all levels, to foster the open sharing of ideas, discoveries, and resources. Over the last decade, our network has sought to decentralize institutional influence by bringing in fresh perspectives in leadership, drawn from across our growing number of member sites. Both the CBTN executive committee and scientific committee have since welcomed some of the brightest minds in pediatric brain cancer research and treatment to help guide our mission in chairperson positions.
In early November, CBTN’s scientific committee selected Dr. Carl Koschmann, MD of the University of Michigan as its newest co-chair, where he joins Dr. Michael Prados, MD of UCSF Benioff Children’s Hospital in this leadership role. A CBTN collaborator since 2016, Dr. Koschmann currently practices as a Pediatric Neuro-Oncologist in the Department of Pediatrics and is a Principal Investigator of an independent translational Pediatric Neuro-Oncology laboratory at the Chad Carr Pediatric Brain Tumor Center at the University of Michigan. His work in the clinic and lab complement and drive each other, resulting in a clear goal to improve therapies for children and young adults with brain tumors.
Recently, we spoke with Dr. Koschmann about his current areas of research, including clinical trials development in pediatric diffuse midline glioma (DMG) and precision medicine, as well as his goals in this leadership role within CBTN, which includes leading new preclinical research efforts and further connecting an international community of physicians and researchers.
CBTN: When did you first hear about the Children’s Brain Tumor Network? What about the CBTN research model seemed most valuable for you?
CK: I first heard about CBTN around 5 years ago – when multiple centers we were collaborating with mentioned that we should look into the data and tissue available through CBTN. Since then, my projects in the lab and clinic were increasingly involving collaborations with CBTN members and datasets and I was drawn to the scale of data and the philosophy of pure collaboration.
CBTN: Over your time as a CBTN collaborator, how has the growth of this network positively impacted your work? Have there been any advances in the lab or in the clinic that your team has made as a result of accessing and sharing resources through CBTN?
CK: The scale of sites, data, investigators and the shared philosophy of collaboration has accelerated the pace of many projects I am working on – especially those with analysis of tumor genetic data. As an example, our work with Drs. Sebastian Waszak and Javad Nazarian has uncovered new mechanistic understanding of DMG response to the imipridone ONC201 in analysis of patient sequencing data. These collaborations have infused us with new ideas, some of which have led to new projects in the lab, and preliminary data for external grants.
CBTN: Apart from this new leadership role, you already contribute quite a lot of your time and expertise within CBTN. For one, you apply your concentration in diffuse midline glioma research in leading the CBTN/PNOC clinical trials working group in DMG/DIPG. Can you tell us a little about the membership within this working group and some of the projects the group is leading?
CK: Yes, I work closely with the PNOC DMG working group, led by Drs. Sabine Mueller, Javad Nazarian and myself. Through this working group, and our other clinical Co-PIs (Drs. Cassie Kline, Andrea Franson and Mike Prados), I serve as Co-PI for two recently opened PNOC clinical trials in DMG (PNOC22/23). My focus is on helping to design and analyze some of the correlate samples from these trials (target validation tumor PK/PD and CSF/plasma correlate markers). Additionally, I am leading efforts to deposit pediatric brain tumor sequencing datasets from U of M (MiOncoseq, PIs Drs. Arul Chinnaiyan and Rajen Mody) with CBTN. We will be using MiOncoseq as the primary sequencing modality for PNOC22/23, with data prospectively deposited in CBTN.
CBTN: You also led a team to create the CNS Target Agent Prediction, or “CNS TAP” tool, to make the drug selection process more precise in treating high-grade gliomas. Your presentation on CNS TAP at this year’s CBTN Investigator Meeting explored some of the exciting progress you’ve made with this tool, particularly in connection with DIPG and HGG clinical trials including PNOC003 and PNOC008. What’s next on the horizon for the further development of this resource?
CK: Yes the CNS TAP tool is now available online (www.cnstap.org) thanks to efforts of a researcher in my lab, Karthik Ravi. Dr. Andrea Franson and myself have fully integrated CNS-TAP into prospective drug selection in PNOC008. We are in the process of working with Drs. Adam Resnick and Bailey Farrow to transition this tool to be managed at CBTN alongside the other online tools available to researchers and clinicians. Future studies are looking at the incorporation of patient-specific dose response screening data as well as incorporating public pharmacogenomics datasets and tools with Dr. Adam Kraya from CBTN.
CBTN: As Scientific Co-Chair, you’ll also be leading new efforts in preclinical research. Why are preclinical research models so important to advancing childhood brain tumor research, and what is the scope of the new CBTN preclinical research initiative?
CK: I am very excited to help efforts in preclinical research associated with CBTN. This is already a very rich and expansive component of CBTN led internally by Dr. Mateusz Koptyra, along with many exciting initiatives that are unparalleled in any brain tumor research organization. An area that we are expanding and leading in the field is in the integration of real-time drug screening in collaboration with NCATS, Dr. Wechsler-Reya, Dr. Firestein and other groups. This is just one of many exciting concepts that I look forward to help build.
CBTN: When considering the CBTN as a whole, what do you find most promising about the network’s current position within the pediatric brain tumor research landscape, and how do you hope to use your knowledge and experience to help advance the CBTN’s mission as Scientific Co-Chair?
CK: CBTN is comprised of a large group of very talented and innovative data scientists and translational researchers/clinicians along with a shared core value of collaboration and data sharing. This has positioned CBTN to be the largest all-around research platform for pediatric brain tumor research. My own expertise is in translational research in diffuse midline glioma and pediatric high-grade glioma, but perhaps my most useful trait for this role will be in further connecting and building collaborations between researchers, clinicians, funders, data registries and industry. I look forward to pushing the envelope even further in terms of collaboration and real-time data sharing.
CBTN: Progress in childhood brain tumor research requires the talents of a global community, now and into the future. What would you say to scientists and clinicians who are early in their careers or who may be interested in pivoting to pediatric research, to encourage them to partner with the CBTN on its mission?
CK: As is well known, high-risk pediatric brain tumors comprise a dark corner of medicine – with major problems that need to be tackled. We don’t really have a precedent for the personnel, tools and data CBTN has put together – and we don’t have a ceiling on what it can accomplish. I very much believe that clinicians and researchers involved in pediatric brain tumor research with CBTN now and in the future will be a part of major improvements in brain tumor biology understanding and patient outcomes.