Research funded by the National Brain Tumor Society in 2009 is described below.
NBTS is also involved in a number of collaboratively funded research initiatives. For general information on program areas, visit Funded Research.
- 2009 Standard Research Grants
- 2009 Advanced Research Grants
- 2009 Innovation Research Grants
- Download the 2009 Research Programs awards booklet (PDF)
2009 Standard Research Grants
Kenneth Aldape, MD
The University of Texas M.D. Anderson Cancer Center
Houston, Texas
Role of YKL-40-beta-catenin signaling axis in GBM progression and radioresistance
The study investigates the YKL-40 gene. A protein that is produced by this gene is used as a prognostic marker for GBMs (how well patients will respond to therapy). The gene is also expressed by the newly discovered TICs (tumor initiating cells) that are known to self renew. The project's hypothesis is if one silences the YKL-40 gene, then the TICs will not be able to form tumors.
Matched to James F. Petersen Chair of Research
Tumor: GBM
Azad Bonni, MD, PhD
Harvard Medical School
Boston, Massachusetts
Regulation of glioblastoma pathogenesis by EGFRvIII – STAT3 signaling
The STAT3 protein determines when genes are switched on or off. This study investigates STAT3's role in brain tumor growth. It is involved in proliferation of neural stem cells, angiogenesis (growth of blood vessels that nourish the tumor), invasion and immunosuppression, and may be an effective therapeutic target.
Matched to James F. Petersen Chair of Research
Tumor: GBM
Nadia Dahmane, PhD
Wistar Institute
Philadelphia, Pennsylvania
Mechanisms regulating stem cell behavior in glioma
This project studies the role of cancer stem cells in resistance to radiotherapy and chemotherapy. The investigator discovered that the gene znf238 plays a critical role in the Sonic Hedgehog (Shh) signaling pathway (pathways that control cell division for adult stem cells). The project will study how the gene affects Shh signaling in healthy neural stem cells and test the hypothesis that znf238 has a tumor suppressor role.
Matched to James F. Petersen Chair of Research
Tumor: GBM
Arti Gaur, PhD
Dartmouth College Medical School
Lebanon, New Hampshire
Role of mir-10a and mir-10b in regulating the pathology of glioblastoma multiforme
This study focuses on the control of gene expression that contributes to the malignancy of GBMs. The research team will look at two particular microRNAs that control the expression of groups of genes. The hope is that they serve as a diagnostic marker (to indicate whether or how fast the tumor is growing) and as a therapeutic target.
Matched to Paul Daniel Bogart Chair of Research
Tumor: GBM
Samira Guccione, PhD
Stanford University
Stanford, California
Anti-angiogenic targeted-nanoparticle therapy in canine spontaneous brain tumors
This project will evaluate a therapeutic approach using nanoparticles that target a cell surface receptor found on brain tumor blood vessels but not normal blood vessels. The approach has been previously demonstrated to be highly effective against brain tumors introduced into mice. However, mouse models are limited because important clinical characteristics of human cancers are lacking in the models. This study will test this nanotechnology therapeutic approach on spontaneous high grade gliomas in dogs which have some of the characteristics lacking in mouse models.
Tumor: High grade gliomas
Cynthia Hawkins, MD, PhD
The Hospital for Sick Children
Toronto, Ontario
Genome-wide profiling of pediatric diffuse intrinsic pontine glioma
The proposed pediatric project will study the genomics of childhood brain stem cancer in the hopes of pointing to new potential therapeutic targets. Using state-of-the-art, high-resolution techniques, genetic alterations will be examined at multiple levels to provide a complete view of tumor, gene, and pathway alterations. The knowledge amassed through this study will allow researchers to rapidly screen agents already in use or in early adult clinical trials which could swiftly move to trials for pediatric brain stem cancer.
Matched to Kayla Wenger Chair of Research
Tumor: Diffuse intrinsic pontine glioma
Amy B. Heimberger, MD
The University of Texas M.D. Anderson Cancer Center
Houston, Texas
Targeting gliomas with a novel inhibitor of the JAK2/STAT3 pathway
The investigator developed WP1066, an orally delivered STAT3 inhibitor. STAT3 (a protein) functions to both stimulate GBM growth and inhibit the immune system that attacks these same GBM tumors. STAT3 inhibition might simultaneously result in the direct killing of GBM cells and the stimulation of the immune system to attack the same tumor cells. The goal of this project is to study agents that inhibit STAT3, having multiple therapeutic effects, and that will ultimately be evaluated for efficacy in a clinical trial. In addition, the goal is to determine if STAT3 is a prognostic biomarker for survival.
Tumor: GBM
Anita B. Hjelmeland, PhD
Cleveland Clinic
Cleveland, Ohio
Targeting radiation resistance in brain tumor stem cells
The study will focus on a protein expressed at high levels in brain tumor stem cells that supports glioma development and resistance to radiation therapy. Drugs that block this protein are currently being evaluated in clinical trials for other diseases. The goal of this study is to determine if reduction of this protein in brain tumor stem cells can cause their death and sensitivity to radiation therapy, and ultimately to test drugs in clinical trials that inhibit this protein.
Matched to BethAnn Telford Chair of Research
Tumor: High grade gliomas
Eric C. Holland, MD, PhD
Memorial Sloan-Kettering Cancer Center
New York, New York
Investigating the role of DNA damage response in gliomagenesis and "cancer stem cell" resistance to irradiation
This is a gene study of chk2's role as a tumor suppressor. Chk2 is a protein that inhibits cell division and growth. The study plans to identify novel characteristics of a protein involved in the repair of DNA damage, the control of tumor growth, and response of tumors to radiation therapy.
Matched to Billy Grey Chair of Research
Tumor: High grade gliomas, Medulloblastoma
Annie Huang, MD, PhD
The Hospital For Sick Children
Toronto, Ontario
Characterization of cell adhesion pathways in childhood sPNET
This study looks at the genetic makeup and expression of genes involved in the control of cell adhesion in sPNETs (supra-tentorial primitive neuroectodermal tumors). The investigator studied the largest collection of these very aggressive pediatric tumors and discovered that molecules involved in maintaining cell to cell contact of adhesion are often altered. Cell adhesion properties contribute to the ability of tumor cells to migrate to other parts of the central nervous system. The study hopes to learn more about the cell to cell adhesion mechanism and genetics in sPNETs, and their unique characteristics.
Tumor: sPNET
Charles Keller, MD
University of Texas Health Science Center at San Antonio
San Antonio, Texas
Proteasome inhibitor mediated reversal of Shh-driven tumorigenesis
This is a pediatric study for patients with medulloblastoma that investigates if restoring the balance of components of the Sonic Hedgehog (Shh) signaling pathway using a particular drug will stop the tumor growth. This study hopes to lead to a rapid clinical evaluation in pediatric patients since the drug has already been approved for the treatment of leukemia in adults.
Tumor: Medulloblastoma
Anna M. Kenney, PhD
Memorial Sloan-Kettering Cancer Center
New York, New York
YAP1 as an effector of Sonic hedgehog mitogenic signaling in cerebellar development
This pediatric study will compare how the protein YAP1 causes cells to divide in healthy brain and in medulloblastoma, identify its role in medulloblastoma recurrence, and implement genetic engineering to develop new medulloblastoma mouse models based on YAP1 activity. Medulloblastomas arise from rapidly dividing immature brain cells, which divide when they receive an instructive signal from a molecule called "Sonic hedgehog". Researchers recently found that in dividing brain cells Sonic hedgehog turns on YAP1 which can cause cells to become cancerous. Preliminary studies show that YAP1 proteins in medulloblastoma cells survive radiation and cause tumor re-growth, making it an essential target for future therapies.
Matched to Students Supporting Brain Tumor Research Chair of Research
Tumor: Medulloblastoma
Sadhan Majumder, PhD
The University of Texas M.D. Anderson Cancer Center
Houston, Texas
Novel mechanism of glioblastoma tumorgenesis and therapy
This study focuses on the significant question of how brain tumor stem cells renew themselves as well as give rise to mature tumor cells. Investigators will study a novel mechanism that controls the self-renewal activity of normal stem cells that is functioning abnormally in glioblastoma stem cells.
Matched to Lionel Chaiken Chair of Research
Tumor: GBM
Axel H. Schonthal, PhD
University of Southern California
Los Angeles, California
Blocking autophagy and increasing ER stress to improve therapy of GBM
This study focuses on drug resistance and attempts to increase the effect of chemotherapy. Chemotherapy is only effective for a limited time before the tumor recurs. Endoplasmic reticulum stress response (ERSR) may be a factor in drug resistance. The investigator believes that resistance to therapy is due in part to ERSR and refers to it as a potential Achilles heel for brain tumor cells.
This study investigates the role of endoplasmic reticulum stress response (ERSR) on drug resistance. Researchers will evaluate several drugs and drug combinations that can overpower the ERSR and destroy tumor cells. Ultimately, the project hopes to improve patient treatment by enhancing the effect of chemotherapy.
Matched to Steven J. Bryant Chair of Research
Tumor: GBM
Mariano Viapiano, PhD
Ohio State University
Columbus, Ohio
Regulation of tumor cell invasion and survival by fibulin-3, a matrix protein uniquely expressed in gliomas
The study focuses on a novel extracellular protein named fibulin-3, which is absent in healthy brain tissue but abundant in gliomas. Fibulin-3 has been found to play a role in the invasive nature of malignant gliomas. The project will increase our understanding of the mechanisms involved in glioma invasion and survival and potentially identify targets for future therapies.
Matched to Steven J. Bryant Chair of Research
Tumor: Malignant glioma
Paul Watkins, MD, PhD
Kennedy Krieger Institute
Baltimore, Maryland
ACSVL3-A novel therapeutic target in malignant glioma
This project investigates how the blocking of a natural cell growth activity, the making of cell membranes, could be used to eliminate rapidly growing brain tumor cells. The level of one specific enzyme that activates fatty acid synthesis is extraordinarily high in gliomas. This investigator plans to define the role of this fatty acid synthesis enzyme in a well established pre-clinical model of malignant glioma and validate it as a unique therapeutic target.
Matched to Krista Thompson Chair of Research
Tumor: High grade gliomas
William Weiss, MD, PhD
University of California, San Francisco
San Francisco, California
Inhibition of PI3K and Cdks in glioma
This study builds on previous NBTS-funded work that identified a potential drug molecule that blocks PI3K and kills glioma cells (other drugs block PI3K, but don't kill the glioma cells). It is important to note that the activation of PI3K is prominent in gliomas and leads to survival of glioma tumor cells. This study will evaluate different drug and drug combinations that inhibit PI3K as well as inhibiting other enzymes that drive the cell cycle to determine the most effective combination that kills glioma cells. The hope is to quickly advance the most effective drug combinations to clinical trials.
Matched to Benjamin Memmott Chair of Research
Tumor: High grade gliomas
Hai Yan, MD, PhD
Duke University
Durham, North Carolina
The role of HDMX in GBM oncogenesis and chemoresistance
This project studies how a cellular negative regulator of the highly important p53 tumor suppressor is involved in GBM development and drug resistance. The investigator discovered a cancer gene called HDMX that negatively regulates p53 signaling (involved in growth and resistance) and will study its role in tumor development and drug resistance.
Tumor: GBM
Special Projects: Pediatric Low-Grade Glioma (LGG) Initiative
Michael K. Cooper, MD
Vanderbilt University Medical Center
Nashville, Tennessee
Targeting the hedgehog pathway in pediatric low grade glioma
Mark Kieran, MD, PhD
Dana-Farber Cancer Institute
Boston, Massachusetts
A phase II study of RAD001 (everolimus) for children with chemotherapy hemotherapy-refractory progressive symptomatic low grade gliomas
Xiao-Nan Li, MD, PhD
Texas Children's Hospital, Baylor College of Medicine
Houston, Texas
Development of clinically relevant orthotopic xenograft mouse models of childhood low grade glioma from primary tumor tissues
Elizabeth Maher, MD, PhD
University of Texas Southwestern Medical Center
Dallas, Texas
Identification of the molecular signature of progressive JPA
Ian Pollack, MD
University of Pittsburgh
Pittsburgh, Pennsylvania
Peptide vaccine based immunotherapy for pediatric low grade gliomas
Charles D. Stiles, PhD
Dana-Farber Cancer Institute
Boston, Massachusetts
Establishment of a consortium-based tissue bank dedicated to Pediatric LGA
2009 Advanced Research Grants
David Largaespada, PhD
University of Minnesota
Minneapolis, Minnesota
The Neuro-Oncology Genomics Project
This study utilizes sophisticated mouse models that highlight the altered genes and pathways that cause cancer. The models will also be used to test the idea of combination therapies directed at more than one of the altered proteins and signaling pathways.
Matched to Seth Harris Feldman Chair of Research
Tumor: Glioma, Medulloblastoma
James Waschek, PhD
University of California
Los Angeles, California
Critical role of STAT3 in medulloblastoma immune evasion in genetically engineered mice
The objective of this project is to genetically distinguish the consequences of STAT3 activation in medulloblastoma tumor cells vs. the immune cells that invade the tumors. STAT3 activation is thought to be a critical event in the development of brain tumors and a suggested therapeutic target. However, STAT3 is also important for the ability of the immune system to help fight tumors. Genetically engineered mice afford a new possibility to determine mechanisms by which the natural immune response changes as tumors progress from very early to later stages.
Matched to Justin Friedlander Chair of Research
Tumor: Medulloblastoma
2009 Innovation Research Grants
Suzanne Baker, PhD
St. Jude Children's Research Hospital
Memphis, Tennessee
Molecular pathogenesis of diffuse intrinsic pontine gliomas
This pediatric project proposes to identify the genes that are mutated in DIPG (diffuse intrinsic pontine gliomas) using an unbiased approach to evaluate all of the genetic material in the tumors as well as a directed approach to closely examine candidate genes suspected to be mutated in this disease. These studies may identify therapeutic targets and allow comparisons between DIPG, pediatric high grade glioma arising outside the brainstem, and adult high-grade gliomas. Describing the similarities and differences among these diseases may help predict whether advances in another group of gliomas may hold promise for DIPG.
Matched to Sydney Schlobohm Chair of Research
Tumor: Diffuse intrinsic pontine gliomas
Mark W. Kieran, MD, PhD
Dana Farber Cancer Institute
Boston, Massachusetts
Paraffin-based sequencing of the human kinome in pediatric ATRT
This project will study the molecular pathways that drive AT/RT (atypical teratoid rhabdoid tumor) formation and growth. Gene expression array analysis will be performed on a large series (up to 200 samples) of AT/ RT and compared using a number of exploratory analyses. Whole genome mutational analysis in AT/RT has not been previously studied and identification of specific mutations will provide important information on focusing further efforts on specific pathways.
Tumor: ATRT
