Tag Archive for: brain tumor institute

illustration of DNA on computer data background

Q&A with Dr. Rokita: Building bioinformatics infrastructure at the Brain Tumor Institute

Jo Lynne Rokita, PhD, is the director of the new Bioinformatics Core housed within the Brain Tumor Institute at Children’s National Hospital.

Jo Lynne Rokita, PhD, is the director of the new Bioinformatics Core housed within the Brain Tumor Institute at Children’s National Hospital. Dr. Rokita is a cancer genomics leader with 20 years of combined research experience in academia, industry and the government. She’s also a technical and analytical expert in genomics research using microarrays and high-throughput sequencing.

“We are very excited that we were able to recruit Dr. Rokita as director of the Bioinformatics Core Facility,” says Muller Fabbri, MD, PhD, associate center director for Cancer and Immunology Research at Children’s National. “Her Bioinformatics Core will play a central role in providing the Brain Tumor Institute community with unique expertise spanning biology/genetics/genomics and bioinformatics and will propel Children’s National forward as a national and worldwide leader in pediatric brain tumor research.”

Dr. Rokita is overseeing the core’s creation, including bringing both bioinformatics staff and computing infrastructure to the program, which will support the data analysis needs of the institute’s investigators. She recently answered questions about the new core and also talked a little bit about the focus of her own research that will continue at Children’s National.

Q: Why is the Brain Tumor Institute establishing a Bioinformatics Core?

A: Growing the institute’s bioinformatics capabilities was one of the things that leadership wanted to make sure was built into the plan for the record-setting $96 million gift that was received in 2023. There was a clear need among the principal investigators for this type of research support which includes organization, analysis and interpretation of large-scale genetic sequencing and other “-omics” data.

Q: How did you decide to join Children’s National?

A: I was leading a pediatric brain tumor focused bioinformatics team at Children’s Hospital of Philadelphia (CHOP). As a part of the Children’s Brain Tumor Network (CBTN), I worked closely with a collaborator from Children’s National, Brian Rood, MD, medical director of the Brain Tumor Institute. He told me about the opportunity and I was very excited to apply.

Q: How did your previous work prepare you for this role?

A: I’ve spent the past 10 years in the pediatric cancer field with the last six focused on brain tumor research. In my various roles at CHOP, I led multiple large-scale genomic analysis efforts, comprehensive data and methods for which we then provided openly to the community. During my postdoctoral fellowship, these efforts included a large neuroblastoma patient-derived cell line “ENCODE” as well as a resource led in collaboration with multiple institutes and the National Cancer Institute funded by Alex’s Lemonade Stand Foundation (ALSF). We further scaled these efforts to build open analytical platforms to empower researchers to build upon our work doing their own cancer genomic analysis. In collaboration with the Childhood Cancer Data Lab at ALSF, we built the platform that ultimately ballooned into the OpenPedCan includes large amounts of harmonized genomic, epigenomic and proteomic data for patients with pediatric cancer. What’s unique is that the data is all processed in the same way and easily accessible through multiple mechanisms. Researchers can use these data to ask questions about the cancer type they study or genes of interest. For example, genes over-expressed, absent and/or mutated in a specific tumor subtype may lead to a better understanding of how a patient’s cancer may respond to a treatment.

We’ll be bringing some of the workflows we created previously here to Children’s National, and that will allow us to join newly generated internal data with the thousands of data points we’ve already harmonized using these workflows.

Q: Can you give us some examples of how data harmonization benefits the field of pediatric brain tumor research?

A: Harmonizing across institutions and databases will help us increase the number of data points available for study. This is really important for rare types of tumors and are major foci of institute collaborator Adriana Fonseca, MD, and her International Rare Brain Tumor Registry program. The Bioinformatics Core will support data organization and analysis for this effort, which aims to sequence the rarest brain tumors — those that make up between only 3% and 5% of all brain tumors. If all the data is analyzed the same way, we can combine multiple studies to increase our total dataset, which in turn may reveal new biomarkers and new subtypes of those tumors. It is critical that we continue to build these data resources in a way that they can be accessed by everyone doing this work. Having dedicated support systems for these functions will push the research farther, faster.

Q: As this work gets underway, what is the core’s main function?

A: As this initiative gets underway, the Bioinformatics Core’s primary goal is to empower investigators by streamlining and centralizing data analyses. We help researchers transfer sequencing data into secure cloud storage, organize newly generated records and prepare those datasets for in-depth study. Our bioinformatics scientists then perform downstream analyses to address the specific questions posed by each investigator. On the backend, we collaborate with information technology at Children’s National to develop a robust infrastructure that supports these activities efficiently. By offering these services in-house, we aim to ensure our investigators have seamless, comprehensive support—ultimately driving innovation and accelerating research progress.

Q: What is “open science” and why is it important in bioinformatics?

A: One of our big focus areas is open science, meaning our goal is to push data and code out into the community so that researchers can easily reproduce and build upon our findings. I’m excited to bring the principles of open science, code sharing and data sharing to the Bioinformatics Core.

Making resources open makes it easier for teams to work together across institutions and research programs. It is also going to benefit patients because people can reuse the code and move towards cures faster. For example, we try to package an entire manuscript’s code when we provide our data so it’s clear how the analyses were done.

Q: What is your particular research passion?

A: I work in several research areas and with many brilliant collaborators. One of our focus areas is understanding how RNA splicing can contribute to pediatric brain tumors to create a change in a protein. We have recently identified tumor-specific splice events in some pediatric brain tumor types and will be partnering with Dalia Haydar, PharmD, PhD, to create therapeutic approaches to targeting these. We are also developing a user-friendly application for mining the large amount of splicing data in pediatric brain tumors.

Another focus of our lab is understanding how the patient’s host genome (alterations inherent in their blood DNA) influences the tumor’s genetics. For example, we’ve just preprinted a study connecting inherited variants to tumor genetics and patient outcomes.

Finally, we are interested in how differences in race, ethnicity and social determinants of health influence survival and treatment outcomes for children with brain tumors.

I am passionate about data sharing, code reproducibility and promoting open science in general.

Q: Is there any specific reason you decided to focus your work around brain tumors and pediatric brain tumors?

A: My cousin passed away from a brain tumor when I was in high school. They didn’t have molecular diagnosis then, but he had a brainstem glioma, likely a diffuse midline glioma. In graduate school, I studied addiction genetics and became fascinated with the brain and towards the end, cancer. As an alumna of Penn State, I was actively involved in philanthropic events raising money for their Dance MaraTHON supporting children with cancer. I was lucky to land a postdoc at CHOP and lean into subsequent roles which allowed my passion for this field to grow.

Q: Last question — What do you do with your time when you are not studying pediatric brain tumor data?

A: I enjoy being with my family, observing my children learn and grow, and listening to music.

child in hospital bed

$96 million philanthropic investment will transform rare pediatric brain tumor research and care

child in hospital bedChildren’s National Hospital announced a $96 million investment from an anonymous donor family to transform rare childhood brain tumor research and care. The donation, which strengthens our globally recognized leadership in the field, is one of the largest in the hospital’s history.

Children’s National will harness the investment to recruit more top talent and advance the most promising research. This will produce safer, more effective treatments. It also will elevate standards of care to help children with rare brain tumors thrive for a lifetime.

The big picture

Brain tumors are the most common solid tumors affecting children. They are especially challenging in kids because their brains are still developing. The disease and current treatments can put them at risk for lifelong complications.

The anonymous family’s investment provides new hope for patients who face rare and often challenging brain tumor diagnoses — in the Washington, D.C., community and around the world.

“This incredible partnership will lift up one of the nation’s top pediatric brain tumor programs into the stratosphere,” said Kurt Newman, M.D., president and CEO of Children’s National. “It will immediately propel our best-in-class research and care, allowing us to bring new therapies to children with brain tumors. This fundamentally changes the healthcare journey and long-term outcomes for children and their families.”

Why it’s important

This transformational investment will have a far-reaching impact on our ability to save and improve the lives of children with brain tumors. Funds will fuel collaborative breakthroughs across a range of scientific and psychosocial approaches.

The partnership will supercharge highly individualized and promising treatments for children with brain tumors. We will radically transform the research landscape with a focus on:

  • Low intensity focused ultrasound (LIFU) – Advancing laboratory research and a clinical program designed to treat childhood brain tumors with LIFU therapy
  • Cellular immunotherapy – Testing new gene-engineered immune cell products and accelerating their integration into standards of care
  • Rare Brain Tumor Program – Propelling new clinical trials through the hospital’s national and global leadership in pediatric brain tumor consortia. Already, Children’s National is leading a new collaborative with hospitals in North America, South America and Europe to better understand and find novel treatments for these rare diseases
  • Neurosurgery innovation – Exploring multiple ways to perform safer, more effective neurosurgery and developing new methods to enhance drug/agent delivery
  • Precision medicine – Recruiting leading scientists to advance biology-informed therapies that can be targeted for children across a spectrum of brain tumors
  • Good Manufacturing Practices (GMP) facility – Expanding our GMP, one of the first standalone facilities at a children’s hospital in the country, to translate new discoveries into clinical trials more rapidly
  • Additional priorities including expansion of clinical research infrastructure and growth of bioinformatics, brain tumor repository and molecular diagnostics initiatives

The partnership also transforms how we approach care. It will power our pursuit of psychosocial, behavioral health and neuroscientific initiatives to help kids live well and cope with the unique circumstances of their diagnosis. We will focus on:

  • Lifetime health and wellness – Building a world-class research and clinical care program to shape a new paradigm for supporting a child’s physical and emotional health during and long after cancer treatment
  • Child Mental Health & Behavioral Brain Tumor Lab – Establishing a robust neuro-oncology mental health program that delivers timely interventions and specialized psychiatric care for patient well-being
  • Additional priorities including a new Neuroscience Nursing Excellence Program and growth of psychosocial support activities that bring comfort and encouragement to children during their treatment journey

Children’s National is proud to lead the way to a better future for pediatric rare brain tumor patients and expand our internationally recognized capabilities for neuro-oncology care.

graphic abstract for brain tumor paper

First large-scale proteogenomic analysis offers insights into pediatric brain tumor biology

graphic abstract for brain tumor paper

In the first large-scale, multicenter study of its kind, researchers conducted comprehensive analysis yielding a more complete understanding of pediatric brain tumors (PBT), which are the leading cause of cancer-related deaths in children. Researchers from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Children’s Brian Tumor Network (CBTN) generated and analyzed proteomic data, which identifies common biological characteristics among different tumor types. The consortia consist of collaborators from the Icahn School of Medicine at Mount Sinai, National Cancer Institute, Fred Hutchinson Cancer Research Center, Children’s National Hospital and Children’s Hospital of Philadelphia. The study, published in Cell on November 25, 2020, provides a clearer understanding of the molecular basis of pediatric brain tumors and proposes new therapeutic avenues.

The molecular characterization of brain tumors has largely hinged upon the presence of unique alterations in the tumor genome ignoring the many layers of regulation that exist between DNA and the functional biology of the tumor cell that is actuated by proteins. The integration of proteomic data identifies common biological themes that span histologic boundaries, suggesting that treatments used for one histologic type may be applied effectively to other tumors sharing similar proteomic features.

Brian Rood, M.D., medical director of the Brain Tumor Institute and associate professor of pediatrics in the Center for Cancer and Blood Disorders at Children’s National Hospital, participated in this study and explains the importance of what the team discovered.

Q: Why was it important that researchers came together to do this work?

A: Comprehensive characterization of the fundamental biology of pediatric brain tumors, including the proteogenomic analysis done in this study, is essential to better understand and treat pediatric brain tumors.

Our study is based on the recognition that proteomics and phosphoproteomics needs to be integrated with other omics data to gain an improved systems biology view of the molecular features of brain tumors. In addition, characterizing biological themes that cross histologic boundaries and cells of origin can suggest extending treatments shown to be effective in one type of tumor to other histologically disparate tumors sharing the same proteomic features.

Proteomic data further reveal the functional impacts of somatic mutations and copy number variations (CNVs) not evident in transcriptomic data alone. Further, kinase-substrate network analyses identify activated biological mechanisms of tumor biology.

This work was only possible because of a unique collaboration between the CPTAC program of the NCI and the CBTN, of which Children’s National is a member.

Q: How will this work advance understanding and treatment of pediatric brain tumors?

A: Pediatric brain tumors have not benefitted from molecularly targeted drugs as much as other tumor types largely because they harbor relatively few gene mutations. Therefore, identifying key pathways to target in these patients’ tumors has been a challenge. The integration of proteomic and phosphoproteomic data with genomic data allows for the construction of a more comprehensive model of brain tumor biology and nominates specific key pathways to be targeted.

Q: What did you find that excites you?

A: Proteomic data revealed a number of findings that were not present in the genomic data. We found evidence to support a molecularly targeted approach to treating craniopharyngioma, a tumor that has previously been unresponsive to chemotherapy. We also found a prognostic marker for high grade gliomas that do not have a mutation in the H3 histone. We were able to identify specific kinases that may dictate the aggressive nature of certain ependymoma tumors. Importantly, we demonstrated the potential of proteomic studies to uncover unique tumor biology, paving the way for more extensive investigations using this approach.

You can find the full study published in Cell. Learn more about the Brain Tumor Institute at Children’s National.


Dr. Rood recently joined a live panel discussion with researchers from the Children’s Brain Tumor Network and the Clinical Proteomic Tumor Analysis Consortium to explore the impact of their landmark study.

Javad Nazarian

Private foundation and researchers partner to cure childhood cancers

Javad Nazarian

Researchers nationally and internally stand the best chance of fulfilling Gabriella Miller’s dream of curing childhood cancers by effectively working together, says Javad Nazarian, Ph.D.

“Thank you for helping me reach my goal.” The handwritten note was penned by Gabriella Miller, a patient treated at Children’s National Health System who ultimately succumbed to an aggressive form of pediatric brain cancer.

Gabriella, then 9 years old, dreamed of curing childhood cancer, including diffuse intrinsic pontine glioma (DIPG), the aggressive pediatric brain tumor that took her life.

Attendees will gather April 14, 2018, for an annual gala held by the Smashing Walnuts Foundation – a group Gabriella started – to celebrate their progress on achieving her goal and to chart future strategic approaches.

“While this foundation was the brainchild of a single person, researchers nationally and internally stand the best chance of fulfilling her dream by working together more effectively,” says Javad Nazarian, Ph.D., M.S.C., the gala’s main speaker. Nazarian is scientific director of Children’s Brain Tumor Institute and is scientific co-chair of the Children’s Brain Tumor Tissue Consortium.

To that end, Children’s National was named a member of a public-private research collective awarded up to $14.8 million by the National Institutes of Health (NIH) to launch a data resource center that cancer sleuths around the world can tap into to accelerate discovery of novel treatments for childhood tumors.

This April, the NIH announced that researchers it funded had completed PanCancer Atlas, a detailed genomic analysis on a data set of molecular and clinical information from more than 10,000 tumors representing 33 types of cancer, including DIPG.

And this January, the NIH announced that it would accept applications from researchers performing whole-genome sequencing studies at one of its Gabriella Miller Kids First research program sequencing facilities. The centers will produce genome, exome and transcriptome sequencing.

Expanding access to these growing troves of data requires a close eye on nuts-and-bolts issues, such as securing sufficient physical data storage space to house the data, Nazarian adds. It’s essential for research teams around the world to have streamlined access to data sets they can analyze as well as contribute to.

“In addition to facilitating researchers’ access to this compiled data, we want to ensure that patients and families feel they are partners in this enterprise by also offering opportunities for them to share meaningful clinical data,” Nazarian says.

Nazarian has been instrumental in expanding the comprehensive biorepository at Children’s National, growing it from just a dozen samples six years ago to thousands of specimens donated by patients with all types of pediatric brain tumors, including DIPG.

“We are so grateful to our patients and families. They share our passion for finding cures and validating innovative treatments for pediatric cancers that defy current treatment. They provide funding through their foundations. Families touched by tragedy offer samples to help the next family avoid reliving their experience,” Nazarian says. “It is in their names – and in Gabriella’s name – that we continue to push ourselves to ‘crack the cure’ for childhood brain cancer.”

Javad Nazarian named scientific director of the Brain Tumor Institute

Javad Nazarian

Javad Nazarian, Ph.D., has been named scientific director of the Brain Tumor Institute of the Children’s National Health System. Since 2006, Dr. Nazarian has been an active member of the Brain Tumor Institute, contributing to the advancement in understanding pediatric brain tumors.

He has been instrumental in his role as a Principal Investigator in the Center for Cancer and Immunology Research where his laboratory actively investigates the molecular mechanisms of diffuse intrinsic pontine gilomas (DIPGs) and establishes preclinical models of pediatric brain tumors.

Dr. Nazarian has also contributed to the expansion of the comprehensive biorepository at Children’s National, growing from 12 samples six years ago to more than 3,000 specimens donated by more than 900 patients with all types of pediatric brain tumors, including DIPG. Recently he was appointed Scientific Co-chair of the Children’s Brain Tumor Tissue Consortium.