Pediatric Brain Tumor Foundation Institute Programs

It was with an eye to the future that we committed the Foundation to encouraging collaborative pediatric brain tumor research. In 2003, we granted $6 million to Duke University to found the Pediatric Brain Tumor Foundation Institute at Duke. The Institute's staff engage in multiple research projects and collaborate with researchers in the United Kingdom and Germany.

At the time, we announced our intention to expand the PBTF Institute initiative so that additional research collaborations could be formed. That opportunity came in 2005 when we committed a total of $900,000 over three years to support pre-PBTF Institute planning grants at three leading research institutions: University of California, San Francisco, Childrens Hospital Los Angeles and the Hospital for Sick Children in Toronto, Canada.

Listed below are the research projects supported by the PBTF through our Institute program in 2005:

Pediatric Brain Tumor Foundation Institute at Duke

Director: Darell Bigner, M.D., Ph.D.

Project 1: Establishment of Cell Lines, Xenografts and Monoclonal Antibodies, PI: Darell Bigner, M.D., Ph.D.
Project 2: Serial Analysis of Gene Expression of Childhood Brain Tumors, Hai Yan, M.D., Ph.D.
Project 3: Altered Signal Transduction, Pathways and Small Molecule Inhibitors, Jeremy Rich, MD.
Project 4: Gene and Radiotherapy, PI: Michael Zalutsky, Ph.D.
Project 5: Definition of Non-AGT/DNA Mismatch Repair Deficiency Mechanisms of Resistance to Temozolomide, PI: Henry Friedman, M.D.
Project 6: Fibro Growth Factor as a Therapy for Medulloblastoma, Rob Wechsler-Reya, Ph.D.
Project 7: Investigational New Drug and Reagent Preparation Core, PI: Michael Granger, Ph.D.
Project 8: Tissue Bank Core, PI: Roger McLendon, M.D.
Project 9: Pilot Project Core, PI: Darell Bigner, M.D., Ph.D.

2005 PBTF Institute Award

University of San Francisco:
Program on Pediatric Brain Tumor Biology and Therapeutics, Mitchel Berger, M.D. Principal Investigator

Certain types of pediatric brain tumors, brain stem glioma and medulloblastoma in particular, are associated with poor outcomes. This research proposal from UCSF includes five projects that address these problems using new approaches. Project 1 focuses on the developmental origin of brain stem gliomas with the overall aim of identifying stem cells within the brain stem that may cause malignant gliomas. Project 2 will grow pediatric brain tumors directly in hosts. This approach facilitates a detailed characterization of these tumors and also provides a resource for other projects. Project 3 explores the role of a specific oncogene, NMYC, that is important for the development of medulloblastoma. This project will also study the effect of an exciting new family of agents that target this oncogene. Project 4 will study medulloblastoma using a number of new techniques that allow the entire genome to be analyzed. Also, a technique called siRNA inhibition will be used to turn off specific genes that may drive tumor growth. Project 5 will study two new strategies, convection-enhanced delivery and intra-nasal delivery, to directly place chemotherapy drugs into the brain stem. Finally, these projects will be supported through an Administrative Core and a Pediatric Brain Tumor Bank.

Project 1: Central Nervous System Development and Brain Stem Glioma Tumorigenesis
David H. Rowitch M.D., Ph.D.,and Arturo Alvarez-Buylla, Ph.D.
Project 2: Pediatric Brain Tumor Xenograft Panel, C. David James, Ph.D.
Project 3: MYCN and Medulloblastoma Tumorigenesis, William A. Weiss, M.D., Ph.D.
Project 4: Genome-based Marker and Therapy Development in Pediatric Brain Tumors,
J. Graeme Hodgson, Ph.D.
Project 5: Convection-enhanced and Intra-nasal Delivery of Therapeutic Agents,
Natlin Gupta, M.D., Ph.D.
Project 6: Administrative and Statistical Core: Mitchel S. Berger, M.D.
Project 7: Tissue Bank and Neuropathology Core: Scott VandenBerg, M.D., Ph.D.

2005 PBTF Institute Award

Children’s Hospital Los Angeles, Biology and Therapy of Pediatric Brain Tumors:
Saving Lives, Saving Neurons, Robert Seeger, M.D., Principal Investigator

Improvement in survival and quality of life for children with brain tumors will come from a better understanding of the these tumors. The research focuses on tumors diagnosed before 10 years of age. Project 1 determines the "molecular portrain" of medulloblastomas to discover genes that are important in cancer behavior and that may be targets for treatment. Project 2 investigates how medulloblastomas and gliomas create new blood vessels which allow tumors to grow, and develops treatments to kill blood vessels in order to shrink tumors. Project 3 studies how cells of the immune system called natural killer T cells (NKT) can be used to treat gliomas. Project 4 tests anti-cancer drugs for activity against childhood brain tumors using a laboratory-based test system that can determine the best way to combine different drugs. Project 5 images brain stem gliomas in patients to obtain information for developing and evaluating new therapies. These studies will advance knowledge about childhood brain tumors and will lead to more effective diagnosis, classification, and treatment.

Project 1: Genomics, Robert C. Seeger, M.D.
Project 2: Microenvironment and Angiogenesis, Anat Erdreich-Epstein, M.D., Ph.D.
Project 3: Immunotherapy, Leonid Metelitsa, M.D., Ph.D.
Project 4: Experimental Therapeutics, Patrick Reynolds, M.D. Ph.D.
Project 5: Molecular Imaging, Stefan Blumi, Ph.D.
Core 1: Pathology, tissue banking and cell lines, Floyd Giles, M.D.
Core 2: Pediatric Brain Tumor Core, Anat Erdreich-Epstein, M.D., Ph.D.
Core 3: Imaging, Mike Rosol, Ph.D.
Core 4: Biostatistics, Richard Sposto, Ph.D.

2005 Pediatric Brain Tumor Foundation Award

Hospital for Sick Children, James Rutka, M.D., Ph.D.; Principal Investigator

In the past, the limited number of genes identified as important in the pathogenesis of medulloblastoma have been identified using a candidate gene approach. We hypothesize that recently developed techniques in genomics and molecular genetics will allow us to identify novel oncogenes and tumor suppressor genes not previously suspected as playing a role in the etiology of medulloblastoma. Identification of the key genetic events in the intitiation, maintenance, and progression of medulloblastoma will allow for the rational design of targeted therapeutic strategies.

Project 1: Identification of Interstitial Germline Deletions in Children with Complex Clinical Syndromes that include Medulloblastoma, Michael Taylor, M.D. Ph.D, Eric Bouffet, M.D.
Project 2: High Resolution Genotyping of a Large Cohort of Pediatric Medulloblastomas, Michael Taylor, M.D., Stephen Scherer, Ph.D., Jim Rutka, M.D., Ph.D.
Project 3: Ultrahigh Resolution Genotyping of Highly Purified Medulloblastoma, Peter Dirks, M.D., Ph.D.
Project 4: Identification of Truncating Mutations in Pediatric Medulloblastoma, Peter Dirks, M.D., Ph.D., Jim Rutka, M.D., Ph.D., Michael Taylor, M.D., Ph.D.