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One Quarter Equals Big Change Oct 2017 – #PBTF

Oct 2017 PBTF $446.75

Another successful month for Aardvark Trash and PBTF.  Curethekids.org received $446.75 in October our largest donation to date.  As we grow, the donations grow thanks to our wonderful customers.

Below is a list of the current projects that PBTF is supporting with our donations (directly from Curethekids.org):

Research Projects

Epigenetic alterations define lethal CMP-positive ependymomas of infancy
Principal investigators: James T. Rutka, MD, PhD, FRCSC and Michael D. Taylor, MD, PhD
Institution: The Hospital for Sick Children, Toronto, Canada
Award: $1,000,000 over three years

The principal investigators started a worldwide consortium, GENE (Global Ependymoma Network of Excellence) consisting of scientists, pathologists and clinicians from more than 30 centers around the world. Cumulatively, the members have contributed more than 400 PF-ependymomas with matched clinical data to the tumor bank in Toronto.

With funding from the PBTF, the PIs will continue to grow the tumor bank and develop biomarkers to discern PFA (poor prognosis) from PFB (better prognosis) ependymoma in a CLIA-certified manner. They will also develop additional human PFA xenograft models to study epigenetic agents for therapy and to study biology and response to novel agents in the relapse setting.


Development of a peptide vaccine for DIPG

Principal investigators: John Sampson, MD, PhD, MBA, Oren Becher, MD and Kendra Congdon, PhD
Institution: Duke University
Award: $400,000 over three years

Immunotherapy promises an exquisitely precise approach to treatment. However, it is limited in this role due to a lack of consistently expressed and tumor-specific antigens. Recently, a point mutation was discovered that provides a highly conserved and tumor-specific mutation, H3.3K27M, in 60 percent of DIPGs. Research objectives are to maximize immunogenicity of an H3.3K27M-containing peptide, to optimize vaccination timing in combination with radiation therapy in a murine model of H3.3K27M positive DIPG, and to perform IND-enabling studies.


A novel peptide vaccine targeting CMV antigens in recurrent medulloblastoma

Principal investigators: Eric Thompson, MD
Institution: Duke University
Award: $200,000 over two years

Recent findings have shown that cytomegalovirus (CMV) antigens are expressed in 92% of medulloblastoma cases. Targeting CMV antigens through peptide vaccination is therefore a candidate treatment strategy for this type of brain tumor. This novel strategy will be tested in a pilot clinical trial of a rationally-designed vaccine formulation containing multiple CMV peptides. The trial will enroll children with recurrent medulloblastoma and the primary goals are to determine safety and immunogenicity.


The oligodendrocyte developmental methylome to characterize progenitors for pediatric glioma

Principal investigators: Arturo Alvarez-Buylla, PhD and David Rowitch, MD, PhD
Institute: University of California, San Francisco
Award: $300,000 over three years

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.


Personalized treatment strategies for DIPG

Principal investigators: Sabine Mueller, MD, PhD, Nalin Gupta, MD, PhD and Joseph Costello, PhD
Institution: University of California, San Francisco
Award: $300,000 over three years

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. This clinical feasibility study is being conducted through the Pacific Pediatric Neuro-Oncology Consortium.


Targeting tumor-associated inflammatory cells to ameliorate radiation-induced cognitive changes

Principal investigators: Nalin Gupta, MD, PhD and Susanna Rosi, PhD
Institution: University of California, San Francisco
Award: $150,000 over three years

Radiotherapy 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.


Targeting Wnt-driven angiogenesis in pediatric glioma

Principal investigators: David Rowitch, MD, PhD and William Weiss, MD, PhD
Institution: University of California, San Francisco
Award: $150,000 over three years
Funding partner: Bryan’s Dream Foundation

The Rowitch laboratory has shown that oligodendrocytes maintain a Wnt-activated program of angiogenesis at postnatal stages (Yuen et al., 2014, Cell in press). 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.

A novel peptide vaccine targeting CMV antigens in recurrent medulloblastoma
Principal investigators: Eric Thompson, MD
Institution: Duke University
Award: $200,000 over two years
Funding partner: Catching Up with Jack


Core Resources

Biorepository, stem cell lines and xenografts
Principal investigators: Roger McLendon, MD and Stephen Keir, DrPH
Institution: Duke University
Award: $300,000 over three years
Funding partner: The Kyrie Foundation

Funding from the PBTF to the Biorepository Core provides for light microscopic and molecular analysis on all banked specimens in order that researchers have access to histologically and genotypically characterized tumor samples for diagnostic assessments in preclinical and clinical studies. In addition, funding supports ongoing development of pediatric brain tumor cell lines and patient-derived xenografts at Duke that enable the study of phenotypic and functional heterogeneity, the characterization of tumor subtypes, and preclinical drug testing. The resources of the core facilities are made available to researchers at Duke and other institutions.


Cell lines, animal models and tumor tissue bank

Principal investigators: Joanna Phillips, MD, PhD and Theodore Nicolaides, MD
Institution: University of California, San Francisco
Award: $100,000 over three years

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 Research Center. They are also made available to researchers at other institutions.