The Pediatric Brain Tumor Foundation Institute at Duke was founded in 2003, and is directed by Darell D. Bigner, M.D., Ph.D. The Institute is devoted exclusively to pediatric brain tumor research. The primary goal of the Institute is to develop innovative and less invasive clinical treatments for children diagnosed with brain tumors. The PBTF Institute at Duke was awarded a second $6 million, six-year grant in 2008. The Duke Institute collaborates extensively with the three PBTF pre-Institutes at the University of Californi.a at San Francisco, Children’s Hospital Los Angeles, and the Hospital for Sick Children in Toronto.
Faculty and Staff
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Congratulations to Anne F. Buckley, M.D., Ph.D. who is the recipient of the 2008-09Pediatric Brain Tumor Foundation Institute at Duke Career Development Award. Dr. Buckley is a neuropathologist who came to Duke in 2008 from the University of California San Francisco. Dr. Buckley’s proposed studies involve generating brain tumors in mice through mutation of known genes in postnatal stem cells, in combination with a new approach to stem cell characterization and culture, and to test the hypothesis that brain stem cells can give rise to brain tumors. The long-term goal of this research is to develop better treatments for pediatric brain tumors. |
Summary of Activities
- Project 1. Molecular Genetic Analysis of Pediatric Brain Tumors
Project 1.a. Systematic Oncogenomic Profiling of Pediatric Astrocytoma
Project Leader: Hai Yan, M.D., Ph.D., Assistant Professor of Pathology
Goals: To perform genome-wide, high-resolution measurement of genomic content changes in pediatric astrocytomas and to determine oncogenic roles of identified genes in pediatric astrocytoma pathogenesis, and to identify mutated genes associated with tumor initiation, growth, spread, or other astrocytoma properties by conducting genome-wide mutation analysis
Project 1.b. Utilization of Combined mRNA and microRNA Expression Profiles to Identify New Therapeutic Opportunities in Pediatric Brain Cancer
Project Leaders: Joseph Nevins, Ph.D., Barbara Levine University Professor of Breast Cancer Genomics; and Bryan Cullen, Ph.D., James B. Duke Professor of Molecular Genetics and Microbiology
Goal: To utilize combined mRNA and miRNA expression profiles to identify new therapeutic targets and potential existing drugs that can specifically function for pediatric brain tumors
- Project 2. Genetics of DNA Damage Response and DNA Repair in Childhood Astrocytic Tumors
Project Leader: Francis Ali-Osman, D.Sc., Margaret Harris and David Silverman Distinguished Professor for Neuro-Oncology Research
Goal: To advance the diagnosis and prognosis of pediatric astrocytic damage response and repair, for therapeutic intervention for this group of childhood tumors
- Project 3. Novel Small Molecule Therapy of Pediatric Brain Tumors Including Tumor Stem Cell Therapy
Project 3.a. Eliminating Brain Cancer Cells Through Apoptosome Activation
Project Leader: Sally Kornbluth, Ph.D., Professor of Pharmacology and Cancer Biology
Goal: To explore apoptosome-activating strategies with the goal of eliminating brain tumor cells while sparing normal brain tissue
Project 3.b. Clinical Treatment of Pediatric Medulloblastoma Using Novel Small Molecule Inhibitors of Smoothened Activity: A Translational Approach
Project Leader: Wei Chen, Ph.D., Assistant Professor of Medicine
Goal: To perform lead compound optimization on promising Hedge-hog/Smoothened inhibitors using known structure-activity relationships (SAR), to identify a molecular tumor signature associated with response to Smo inhibitors, and complete preclinical studies
Project 3.c. Targeting STAT3 as a Novel Therapy for Pediatric Medulloblastomas
Project Leader: Hui-Wen Lo, Ph.D., Assistant Professor of Experimental Surgery
Goal: To determine whether increased STAT3 expression contributes to growth and chemoresistance of medulloblastoma cells, to sensitize them to chemotherapeutic agents, and to determine the in vivo effects of the anti-STAT3 agent in single/combination treatments
- Project 4. Medulloblastoma Cell of Origin and Vaccine Therapy
Project 4.a. Initiation and Propagation of Medulloblastoma
Project Leader: Robert Wechsler-Reya, Ph.D., Assistant Professor of Pharmacology and Cancer Biology
Goal: To identify the origin of medulloblastoma resulting from mutations in the Sonic hedgehog-Patched signaling pathway
Project 4.b. Dendritic Cell Vaccines Targeting Medulloblastoma and Medulloblastoma Stem Cells
Project Leader: John Sampson, M.D., Ph.D., Associate Professor of Surgery
Goal: To develop and evaluate the safety and efficacy of DCs loaded with tumor-derived RNA as vaccines in children with high-risk MB and to determine if the targeting of MBs can be significantly enhanced using subtracted RNA libraries
- Project 5. Peptide and Monoclonal Antibody Therapy of Childhood Brain Tumors
Project 5.a. Targeted Radiotherapy of Medulloblastoma
Project Leader: Michael Zalutsky, Ph.D., Jonathan Spicehandler Professor for Neuro-Oncology
Goal: To utilize radiolabeled somatostatin receptor binding peptides as targeted radiotherapeutics for treating children with medulloblastoma
Project 5.b. Specific Antigen-Targeted Immunotherapy of Medulloblastoma
Project Leaders: Darell D. Bigner, M.D., Ph.D., Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor; and Chien-Tsun Kuan, Ph.D., Assistant Professor of Pathology
Goal: To generate high affinity (binding strength) against identified targets, to further develop improved reagents, and to investigate their capacity to kill MED cells in vitro and in vivo when combined with radiation or toxins
- Core 1. Biorepository Core
Core Leader: Roger McLendon, M.D., Professor of Pathology
Goal: To provide a site for storage of tumor tissues, blood, serum, DNA, RNA and protein as well as data
- Core 2. Cell Lines and Xenografts Core
Core Leaders: Darell D. Bigner, M.D., Ph.D.; and Henry Friedman, M.D., James B. Powell, Jr. Professor of Neuro-Oncology
Goal: To provide preclinical evaluation and testing for agents created in Projects 1-6 for IND application, and to prepare and submit appropriate IND application forms for all proposed reagents resulting from individual projects
- Core 3. Administrative Core
Core Leader: Darell Bigner, M.D., Ph.D.
Goal: To provide day-to-day administration of the PBTF Institute projects and cores
- Developmental Research Program
Leader: Darell Bigner, M.D., Ph.D.
Goal: To provide ‘seed’ money to investigators who may be new to the field of pediatric brain tumor research or investigators who wish to pursue novel research in the field
- Career Development Program
Leader: Darell Bigner, M.D., Ph.D.
Goal: To provide start up funds to young investigators who wish to pursue pediatric brain tumor research
The following Duke Clinical and Research Faculty are members of the Pediatric Brain Tumor Foundation Institute at Duke:
Darell D. Bigner, M.D., Ph.D., Edwin L. Jones, Jr. and Lucille Finch Jones Professor of Cancer Research, Institute Director
David Cory Adamson, M.D., Ph.D., Assistant Professor of Surgery
Francis Ali-Osman, D.Sc., Margaret Harris and David Silverman Professor of Neuro-Oncology Research
Gary Archer, Ph.D., Assistant Professor of Surgery
Melanie Bonner, Ph.D., Assistant Professor of Medical Psychology
Anne F. Buckley, M.D., Ph.D., Neuropathology Fellow
Wei Chen, Ph.D., Assistant Professor of Medicine
Bryan Cullen, Ph.D., James B. Duke Professor of Molecular Genetics and Microbiology
Henry S. Friedman, M.D., James B. Powell, Jr. Professor of Neuro-Oncology
Herbert E. Fuchs, M.D., Ph.D., Associate Professor of Pediatric Neurosurgery
Gerald A. Grant, M.D., Assistant Professor of Pediatric Neurosurgery
Sridharan Gururangan, MRCP (UK), Associate Professor of Surgery
Sally A. Kornbluth, Ph.D., Professor of Pharmacology and Cancer Biology; Vice Dean, Basic Sciences, Duke School of Medicine
Chay T. Kuo, M.D., Ph.D., Assistant Professor of Cell Biology
Nicole A. Larrier, MD, Assistant Professor of Radiation Oncology
Hui-Wen Lo, Ph.D., Assistant Professor of Surgery
Roger McLendon, M.D., Professor of Pathology
Duane Mitchell, M.D., Ph.D., Assistant Professor of Surgery
Joseph Nevins, Ph.D., Barbara Levine University Professor of Breast Cancer Genomics
David A. Reardon, M.D., Associate Professor of Surgery
John H. Sampson, M.D., Ph.D., Associate Professor of Surgery
Robert Wechsler-Reya, Ph.D., Assistant Professor of Pharmacology and Cancer Biology
Hai Yan, M.D., Ph.D., Assistant Professor of Pathology
Michael R. Zalutsky, Ph.D., Jonathan Spicehandler Professor of Neuro-oncology Research
Preston Robert Tisch Brain Tumor Center Pediatric Clinical and Research Staff:
Tarah Buckner, New Patient Coordinator
Nancy Butters, BA, Child Life Specialist
Ginny Calhoun, MSW, LCSW, Pediatric Clinical Social Worker
Jean Hartford-Todd, CCLS, Certified Child Life Specialist
Jeanne Krauser, RN, MSN, CPNP, Pediatric Nurse Practitioner
Kimberly Lynch, RN, BSN, Clinical Research Coordinator
Trish Peters, MEd, Duke Hospital School Teacher
Melody Watral, RN, MSN, CPNP, Pediatric Nurse Practitioner
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