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Javad Nazarian

Children’s National launches Open DIPG Initiative

Javad Nazarian

Javad Nazarian, Ph.D., MSC, has played an important role in establishing the Open DIPG Initiative. He hopes that the Open DIPG Initiative will serve as a model for centralized disease-specific efforts that will bring research findings one step closer to clinical translation.

A collaborative team of doctors and researchers at Children’s National Health System today announced the launch of the Open DIPG Initiative through the Children’s Brain Tumor Tissue Consortium (CBTTC).

The primary goals for the project will be to generate DIPG Omics which will help decipher major molecular characteristics of diffuse intrinsic pontine glioma (DIPG). Specifically, these will include genomics, proteomics, transcriptomics and epigenomics for primary analyses, centralize all DIPG Omics for secondary analyses, integrate the new DIPG data and unify DIPG expertise (data scientists, researchers, new talent, etc.) to analyze the DIPG genomic data.

CBTTC Scientific Co-Chairs Javad Nazarian, Ph.D., MSC, principal investigator, and Adam Resnick, Ph.D., have played important roles in establishing the Open DIPG Initiative. They hope that the Open DIPG Initiative will serve as a model for centralized disease-specific efforts that will bring research findings one step closer to clinical translation.

Pediatric brain tumors are the leading cause of disease-related death in children. Unlike many adult cancers, the causes of pediatric brain tumors remain largely unknown, and common therapies have remained mostly unchanged over the last four decades. To address these challenges, clinicians and researchers have embraced the emergence of sequencing technologies and deep molecular characterization of tumors to define novel, targeted approaches and individualized therapies.

However, harnessing such data-driven approaches has been a challenge due to limited accessibility to datasets and shared discovery platforms that can empower large-scale integration of datasets for worldwide access and cross-disease analyses.

As a part of this initiative, the Open DIPG Initiative has collected, generated and annotated the largest cohort of DIPG genome data to date. Specifically, these datasets contain more than 1,000 genomes associated with pediatric high-grade gliomas, with over 500 DIPG cases. The Open DIPG has been a part of a larger effort known as the Pediatric Brain Tumor Atlas, which aims to uncover the molecular basis of childhood cancers.

Committed to accelerated discovery, the CBTTC is partnering with the Kids First Data Resource Center (DRC) and the newly developed Kids First Data Resource Portal, which was also launched today.

“The combination of consortia-based initiatives, partnerships with foundations and new discovery platforms being announced today, with the support of the National Institutes of Health (NIH), provides for entirely new and transformative ways of doing science on behalf of children with brain tumors,” said Adam Resnick, Ph.D., principal investigator of the Kids First DRC.

The Open DIPG initiative will be launched as a part of the Pediatric Brain Tumor Atlas and has been funded by families as well as the NIH Gabriella Miller Kids First Act fund. The fund was launched in 2015 and named after Gabriella Miller, a former patient at Children’s National who lost her life to DIPG.

Javad Nazarian

Advancing pediatric cancer research by easing access to data

Javad Nazarian

“This is a tremendous opportunity for children and families whose lives have been forever altered by pediatric cancers,” says Javad Nazarian, Ph.D., M.S.C., principal investigator in the Center for Genetic Medicine Research and scientific director of the Brain Tumor Institute at Children’s National.

Speeding research into pediatric cancers and other diseases relies not only on collecting good data, but making them accessible to research teams around the world to analyze and build on. Both efforts take time, hard work and a significant amount of financial resources – the latter which can often be difficult to attain.

In a move that could considerably advance the field of pediatric cancer, the National Institutes of Health (NIH), a body that funds biomedical research in the United States, recently awarded a public-private research collective that includes Children’s National Health System up to $14.8 million to launch a data resource center for cancer researchers around the world in order to accelerate the discovery of novel treatments for childhood tumors. Contingent on available funds, five years of funding will be provided by the NIH Common Fund Gabriella Miller Kids First Pediatric Research Program, named after Gabriella Miller, a 10-year-old child treated at Children’s National.

As principal investigators, researchers at Children’s Hospital of Philadelphia will lead the joint effort to build out the “Kids First” Data Resource Center. Children’s National in Washington, D.C., will spearhead specific projects, including the Open DIPG project, and as project ambassador will cultivate additional partnerships with public and private foundations and related research consortia to expand a growing trove of data about pediatric cancers and birth defects.

“This is a tremendous opportunity for children and families whose lives have been forever altered by pediatric cancers,” says Javad Nazarian, Ph.D., M.S.C., principal investigator in the Center for Genetic Medicine Research and scientific director of the Brain Tumor Institute at Children’s National. “From just a dozen samples seven years ago, Children’s National has amassed one of the nation’s largest tumor biorepositories funded, in large part, by small foundations. Meanwhile, research teams have been sequencing data from samples here and around the world. With this infusion of federal funding, we are poised to turn these data into insights and to translate those research findings into effective treatments.”

Today’s NIH grant builds on previous funding that Congress provided to the NIH Common Fund to underwrite research into structural birth defects and pediatric cancers. In the first phase, so-called X01 grantees—including Eric Vilain, M.D., Ph.D., newly named director of the Center for Genetic Medicine Research at Children’s National—received funding to sequence genetic data from thousands of patients and families affected by childhood cancer and structural birth defects.

This new phase of funding is aimed at opening access to those genetic sequences to a broader group of investigators around the globe by making hard-to-access data easily available on the cloud. The first project funded will be Open DIPG, run by Nazarian, a single disease prototype demonstrating how the new data resource center would work for multiple ailments.

DIPG stands for diffuse intrinsic pontine glioma, aggressive pediatric brain tumors that defy treatment and are almost always fatal. Just as crowd sourcing can unleash the collective brainpower of a large group to untangle a problem swiftly, open data sharing could accomplish the same for childhood cancers, including DIPG. In addition to teasing out molecular alterations responsible for making such cancers particularly lethal, pooling data that now sits in silos could help to identify beneficial mutations that allow some children to survive months or years longer than others.

“It’s a question of numbers,” Dr. Vilain says. “The bottom line is that making sense of the genomic information is significantly increased by working through large consortia because they provide access to many more patients with the disease. What is complicated about genetics is we all have genetic variations. The challenge we face is teasing apart regular genetic variations from those genetic variations that actually cause childhood cancers, including DIPG.”

Nazarian predicts some of the early steps for the research consortium will be deciding nuts-and-bolts questions faced by such a start-up venture, such as the best methods to provide data access, corralling the resources needed to store massive amounts of data, and providing data access and cross correlation.

“One of the major challenges that the data resource center will face is to rapidly establish physical data storage space to store all of the data,” Nazarian says. “We’re talking about several petabytes—1,000 terabytes— of data. The second challenge to address will be data dissemination and, specifically, correlation of data across platforms representing different molecular profiles (genome versus proteome, for example). This is just the beginning, and it is fantastic to see a combination of public and private resources in answering these challenges.”