Pediatric Brain Tumor Foundation Institute at UCSF

Pediatric Brain Tumor Foundation Institute at UCSF

As the largest non-governmental source of funding for childhood brain tumor research, the Pediatric Brain Tumor Foundation (PBTF) is dedicated to eradicating childhood brain tumors through supporting medical research, increasing public awareness, and providing educational and emotional support to children and families.

The PBTF has established a world-class research institute at UCSF to define the poorly understood basic biology of several types of childhood brain tumors and improve therapies.

The biology of pediatric brain tumors is not as well understood as that of adult brain tumors, and as a result new therapies have been slow to develop. The research program of the PBTF Institute at UCSF focuses on medulloblastoma and brainstem glioma – alternately the most common and least treatable types of pediatric brain tumors. 


Project Summaries

The Oligodendrocyte Developmental Methylome to Characterize Progenitors for Pediatric Glioma

Principal Investigators: David H. Rowitch MD, PhD and Arturo Alvarez-Buylla PhD 

To better understand pediatric glioma origins, it is important to determine the precise stages of oligodendrocyte progenitor cell (OPC) development targeted by oncogenic mutations. The broad objective of this proposal is to use the methylome as a new index of oligodendrocyte developmental character and use this data to interrogate OPC-like character across different subtypes of human pediatric gliomas from brain stem and forebrain. 

Targeting Tumor-associated Inflammatory Cells to Ameliorate Radiation-induced Cognitive Changes

Principal Investigator: Nalin Gupta MD, PhD

Radiation therapy can cause late effects including progressive cognitive dysfunction. The activation of inflammatory pathways that occur along with tumor recurrence and after cranial irradiation produce many adverse effects, and no treatment is effective. The experiments proposed in this project will help provide a detailed understanding of macrophage accumulation in a rodent brain tumor model, and how modulating this response may affect cognitive performance. 

Personalized treatment strategies for DIPG

Principal Investigator: Sabine Mueller MD, PhD

Mutations in the gene encoding for histone H3.3 (K27M and G34V/R) have been reported as molecular drivers in pediatric HGGs. Moreover, the presence of K27M mutation correlates with worse clinical outcome. PIs will perform whole exome sequencing and gene expression profiling of tumor tissue from children newly diagnosed with DIPG to explore the genomic heterogeneity and to identify key alterations associated with treatment resistance and progression. 

Targeting Wnt-driven Angiogenesis in Pediatric Glioma

Principal Investigators: David Rowitch MD, PhD and William Weiss MD, PhD

The Rowitch laboratory has shown that oligodendrocytes maintain a Wnt-activated program of angiogenesis at postnatal stages (Yuen et al., 2014, Cell). Moreover, many laboratories have shown conservation of oligodendrocyte-like features in human glioma. Therefore, PIs will test the hypothesis that gliomas have co-opted a mechanism for angiogenesis that is normally required during CNS development. This study may identify a novel target for anti-angiogenic therapy.

Core Resources: Cell Lines, Animal Models, Tumor Tissue Bank

Principal Investigators: Joanna Phillips MD, PhD and Theodore Nicolaides MD

Biospecimens obtained directly from the operating room during pediatric brain tumor resections are acquired, molecularly characterized, and used to establish tumor cell lines and intracranial xenografts. These Core resources, developed and maintained on an ongoing basis, are invaluable to help detect new therapeutic targets and to test novel therapies in animal models of the disease, guiding and improving future clinical therapies in pediatric brain tumor patients. The resources of the UCSF Core facility are an essential component of the UCSF Brain Tumor Center. They are also made available to researchers at other institutions.