BILLY GREY GRANT RECIPIENTS
Dr. Paul Mischel, UCSD and Ludwig Institute of Cancer Research
Dr. Paul Mischel's research team discovered how glioblastoma (GBM) brain tumor cells are addicted to cholesterol. The tumors exploit the brain's unique metabolism to import vast amounts of cholesterol into the cells. This creates a potential vulnerability in the cancer cells, because if researchers can attack the mechanisms that tumor cells use to import cholesterol then they could potentially halt the cancer's growth.
2014 - 2016
National Brain Tumor Society Defeat GBM Initiative
Dollars raised from 2014-16 have funded new research initiatives including Defeat GBM carried out by an all-star collaboration of brain tumor researchers spanning the country. (www.defeatgbm.org.) The initiative has discovered new strategies to target potential vulnerabilities in GBM and identify new drug development strategies.
2012 - 2013
Alexandra Joyner, PhD
Memorial Sloan Kettering Cancer Center, New York, NY
Identification of genes and cell behaviors regulated by Shh/Gli2 signaling in the cell of origin of a major subtype of medulloblastoma using novel genetic tools in mouse models Memorial Sloan Kettering Cancer Center.
Markus Bredel, MD, PhD
University of Alabama, Birmingham
Systems Biology Approaches to Brain Tumor Research National Brain Tumor Society (NBTS) has announced the recipients who will receive grants from the largest research initiative it has ever funded – the Mary Catherine Calisto Systems Biology Initiative.
Integrated pharmacogenomic/pharmacokinomic approach to optimize GBM therapy The multidisciplinary team will address two challenges in developing novel glioma therapies: targeting tumors with focused personalized treatments and recurrence. New algorithms will be designed to create a glioma specific network that informs effective therapeutic strategies.
Mark W. Kieran, MD, PhD
Dana Farber Cancer Institute, Boston, MA
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. Matched to Billy Grey Chair of Research.
Eric C. Holland, MD, PhD
Memorial Sloan-Kettering Cancer Center, New York
Investigating the role of DNA damage response in gliomagenesis and “cancerstem 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.
Tumor: High grade gliomas, Medulloblastoma
2007 - 2008
Duane A. Mitchell, MD, Ph.D.
Duke University, NC
Identification and Immunologic Targeting of CMV Antigens Expressed in Malignant Gliomas.
Gregory Hannon, PhD
Cold Spring Harbor Laboratory, New York
Genetic approaches to new therapeutic targets in brain cancer.
Unresponsiveness to present therapies may be due to mutations that negate the cell death pathways that mediate drug-induced killing of tumor cells. One of the key mutations responsible for this effect is loss of the PTEN tumor suppressor. PTEN acts in a pathway that creates a cellular set-point that determines tolerance to a variety of insults, with loss of PTEN creating heightened resistance.
The goal of this proposal is to identify new therapeutic targets for GBM and other brain cancers. Reversing the effects of PTEN mutations alone is insufficient to kill GBM cells. We will search for additional genes that are required either specifically when PTEN is lost or when the effects of PTEN pathways are reversed using an already approved therapeutic. We will focus our search on genes whose products are most amenable to currently available pharmaceutical chemistry.
2005, 2003 - 2004
Duane A. Mitchell, MD, Ph.D.
Duke University, NC
Identification and Immunologic Targeting of CMV Antigens Expressed in Malignant Gliomas
The prognosis for patients diagnosed with malignant gliomas remains very poor and the non-specific nature of standard treatment often results in damage to surrounding normal brain. Immunotherapy directed against tumor-specific antigens holds the potential to target malignant cells more precisely, but it is severely limited because we do not have a strong understanding of the tumor rejection antigens present in human cancers. The recent finding that human cytomegalovirus (HCMV) propagates in a large number of malignant gliomas, without infecting surrounding normal brain cells, promises to direct brain tumor immunotherapy against immunogenic viral targets.
Recent clinical trials highlight the benefit of adoptive immunotherapy, in setting of chemotherapy-induced lymphopenia, as a powerful way to guide the recovering immune system toward anti-tumor recognition. We propose to investigate CMV antigen expression in malignant glioma specimens, and evaluate adoptive immunotherapy following treatment-induced lymphopenia using murine model of CMV-associated astrocytomas.
Evan M. Hersh, MD.
University of Arizona, Tucson, AZ
Dendritic Cell And Dexosome Interaction With Glioblastoma Multiforme.
This project will study how brain tumor cells and substances extracted from them can stimulate the immune system. Research has show that the immune system can be stimulated to kill cancer cells. Immunotherapy, such as cancer vaccines, is showing tremendous promise in brain tumors.
This study will investigate two new approaches to stimulate anti-brain tumor immunity with (1) dendritic cells, special white blood cells that can strongly stimulate the development of killer white blood cells, and (2) dexosomes, microscopic particles derived from dendritic cells and added to dendritic cells and dexosomes and used to stimulate lymphocytes (the body’s immune cells). These laboratory experiments will show how the anti-brain tumor response works and the optimal techniques and conditions to stimulate effective brain tumor immunotherapy.