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
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
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 Nick Gonzales Chair of Research
Tumor: Malignant glioma
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
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 Rachel Markoff Chair of Research
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
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
A gene is delivered to tumor cells that when a harmless prodrug is administered, only tumor cells convert it into a toxin and are killed because of the presence of the introduced gene in those tumor cells.
Matched to James F. Petersen Chair of Research
Andrew Parsa, MD, PhD
Brain Tumor Research Center
University of California, San Francisco, CA
Heat shock protein vaccine development
Matched to Dennis Roth Chair of Research