About the Neurobiology and Brain Tumor Program

Brain tumors are the leading cause of cancer-related deaths in children. Despite recent advances in understanding disease biology, treatment approaches are still lacking for some patients and lead to long-term, debilitating side effects in others. The goal of the Neurobiology and Brain Tumor Program (NBTP) is to improve survival and morbidity of children with brain tumors by developing the most effective, least toxic therapies through a better understanding of disease pathogenesis and normal brain development.

NBTP research focuses on four aims:

  • Elucidating mechanisms driving the pathogenesis of pediatric brain tumors and identifying selective vulnerabilities of subtypes of pediatric brain tumors
  • Developing accurate disease-stratification tools for pediatric brain tumors
  • Incorporating basic and translational findings into innovative clinical trials to advance therapy for pediatric brain tumors
  • Reducing toxicity and improving quality of life for children with brain tumors by incorporating treatment modifications and new interventions into clinical trials informed by translational and clinical research.

Program leaders

Charles WM Roberts
Suzanne Baker, PhD

Department of Developmental Neurobiology

  • Member, St. Jude Faculty 
  • Co-Leader, Cancer Center Neurobiology & Brain Tumor Program
  • Endowed Chair in Brain Tumor Research

Gerard Zambetti
Giles Robinson, MD

Department of Oncology

  • Member, St. Jude Faculty 
  • Director, Division of Neuro-oncology
  • Co-Leader, Cancer Center Neurobiology and Brain Tumor Program

Elucidating mechanisms driving the pathogenesis of pediatric brain tumors and identifying vulnerabilities

Members of the NBTP are focused on understanding the underlying pathogenic processes that drive brain tumor development. Their work has already revealed novel insights into the mechanisms of oncogenic activity of pediatric high-grade glioma (HGG) and medulloblastoma (MB) and facets of how the immune system interacts with brain tumors. 

They identified an oncohistone mutation that affects growth of the deadliest HGG, called high-grade diffuse midline glioma (DMG); furthermore, this mutation shows potential as a therapeutic target. By using patient-derived HGG models, researchers also discovered a clinically relevant compound that disrupted the DNA damage repair mechanism and increased the efficacy of radiation with little toxicity. This is being developed into an upcoming clinical trial.

Single-cell sequencing was used to probe the heterogeneity within and between MB tumors, and the findings helped researchers understand the cellular and developmental states underlying subtype-specific MB biology. Work performed by the NBTP also discovered that G3 and G4 MB—thought to be distinct disease entities—actually comprise a clinical spectrum with biological and clinical overlap. This finding, in conjunction with the discovery of a common predisposition gene for MB, has clinical significance and will shape the way that children with MB are treated.  

The NBTP has advanced CAR T-cell therapy in a variety of ways such as: identified a promising antigen for relapsed or refractory brain tumors such as MB and DMB; enhanced antitumor activity and proliferative capacity of CAR T cells; discovered new molecular targets

The NBTP brings together expertise in fundamental neurobiology, cancer biology, translational research and clinical research to focus its integrated efforts. Members of the NBTP share a common vision that emphasizes the integration of laboratory and clinical research to advance cures for pediatric brain tumors. 

Developing accurate disease-stratification tools

Understanding the relationship between disease and prognosis is an area of active research in the NBTP. The ability to molecularly stratify patients (and disease) based on genetic characteristics and use this information to inform treatment strategies and predict prognoses is transformative. NBTP members have used a variety of state-of-the-art molecular stratification approaches to more comprehensively understand several pediatric brain tumors such as:

  • In a seminal study, NBTP members demonstrated that collection of serial liquid biopsies of cerebrospinal fluid (CSF) can identify those at high risk of treatment failure. The approach is predicted to be especially impactful as this enables relapse to be identified long before disease is evident on imaging, such as by MRI, giving providers an opportunity to intervene earlier than ever before.
  • Historically speaking, a subset of very young children with HGG consistently experience low mortality but high treatment-related morbidity. NBTP-led transdisciplinary studies identified four disease categories and showed that differences in clinical outcomes were biologically driven. The integration of histopathologic and molecular features for diagnosis allowed for this paradigm shifting advance that stands to improve treatment stratification for this vulnerable patient population. 
  • NBTP-led transdisciplinary studies assessing clinical outcomes through DNA methylation-based data accurately connected subgroups to outcomes for patients with ependymoma. Likewise, methylation profiling was used to show the relationship between molecular subgroups of rare central nervous system (CNS) embryonal tumors and clinical outcomes. 
  • Multidimensional molecular evaluation of pineoblastoma and its associated intertumoral heterogeneity identified five tumor subgroups differing in age at diagnosis, propensity for metastasis, cytogenetics and clinical outcomes.

Incorporating basic and translational findings into innovative clinical trials 

The data collected from NBTP-led studies is used to establish new clinical trials that advance therapy, improve survival and lower morbidity in children with CNS tumors. In addition to clinical trials pertaining to the above-mentioned studies, program members are clinically investigating:

  • Locoregional delivery of CAR T cells for pediatric patients with recurrent or refractory primary CNS tumors
  • Novel risk stratified trials for very young children with MB
  • New targeted therapy trials and proton beam radiation trails for patients with low grade-glioma
  • The development of new clinical trials for all CNS tumors  

Reducing toxicity and improving quality of life for children with brain tumors

As survival improves, the NBTP focuses on decreasing morbidity and improving quality of life by better understanding the cause of toxicity-related injury and deploying innovative interventions to mitigate these risks. Studies from NBTP investigators found that young children with brain tumors experience cognitive difficulties affecting quality of life. The study provides new insights for better treatment planning, especially since changes in cognitive function depended on tumor location and surgical factors rather than adjuvant therapy. 

Researchers also showed that cognitive outcomes were improved in patients with craniopharyngioma receiving proton therapy as opposed to a historical cohort. These findings represent a new benchmark to which other regimens can be compared and sets a new practice-changing standard. 

A subset of children who undergo surgical extraction of brain tumors in the posterior fossa will experience posterior fossa syndrome (PFS). PFS significantly impacts speech and affects quality of life. Members of the NBTP identified regions of connectivity in the midbrain that, when damaged, cause PFS. These findings inform surgical planning and even suggest strategies for cognitive rehabilitation. 

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