Funded Projects

Optimizing Outcomes in PLGG Survivorship Study

Pediatric low grade gliomas (PLGG) are the most common childhood brain cancer. Although there are higher survival rates and less severe cognitive complications relative to other pediatric brain tumors, the cognitive outcomes among PLGG are variable and disruption in cognitive abilities and everyday functioning may be subtle in some PLGG survivors.

• Award $364,000 over 3 years (2019-2023)
• Principle Investigators Dr. Tobey Macdonald, Children’s Hospital of Atlanta; Dr. Krista Hardy, Children’s National Medical Center, Dr. Tricia King, Georgia State University Medical Center

Novel Universal Classification of Childhood Low-grade Gliomas Using Clinical, Pathological and Molecular Methods

The recent progress in both molecular understanding and the exciting preliminary results of targeted therapies in pediatric low-grade gliomas (PLGG) created both hope for a new era in front of us but also highlighted urgent issues that will be required to be addressed in the near future to optimize and ensure progress in the field.

Neural Stem Cells and Low Grade Glioma

Building on an initial grant awarded in 2013 focused on the development of human neural stem cell models of PLGA, this study focuses on further exploration in defining and accumulating neural stem cell models for PLGA brain tumors. The central hypothesis of this proposal is that suppression of oncogene-induced senescence in human neural stem cells will allow these cells to tolerate constitutive activation of the RAS/BRAF/MAP kinase pathway, leading to increased growth in vitro and tumorigenicity in vivo. These models will be used to screen for new drug targets that can decrease the growth of PLGA by attacking specific pathways.

MRI Goggles to Improve Pediatric Patients' Diagnostic Experience

Magnetic resonance imaging (MRI) is a physically painless diagnostic tool used to identify and monitor the treatment of brain tumors and other diseases. However, MRI scans can be noisy and uncomfortable for restless, anxious, and claustrophobic patients. Keeping children still long enough to obtain quality images without sedation is often challenging. This grant will support the East Tennessee Children’s Hospital which will be offering noise-canceling, video goggles that provide a cinema experience for pediatric patients undergoing an MRI.

• Award $49,225 over 1 year (2022-2023)
• Project Lead East Tennessee Children’s Hospital (ETCH)

Mouse Modeling Core for Invivo Drug Testing

In addition to supporting a doctorate level scientist to create mouse models of low-grade astrocytoma and to conduct entry-level tests on these cells for drugs that may benefit children with LGAs, this project led by Dr. Chuck Stiles at Dana Farber Cancer Institute takes the next steps in in testing cells for drugs outside the culture dish.

• Principal Investigator Dr. Chuck Stiles, Dana Farber Cancer Institute

Molecular Prognostic Markers for Low-Grade Gliomas

This study will apply the prognostic markers in childhood high-grade gliomas to analyze low-grade gliomas. Researchers led by principal investigator Dr. Ian F. Pollack, Children’s Hospital of Pittsburgh, University of Pittsburgh, will evaluate a series of hypothesis-based markers linked with glioma progression in previous studies, such as MGMT status, proliferation index and genetic alterations.

• Principal Investigator Dr. Ian F. Pollack, Children’s Hospital of Pittsburgh, University of Pittsburgh

Molecular Pathology and Genetics of Low Grade Glioma, Focus on Diffuse Astrocytoma (WHO Grade II)

In a collaborative initiative between St. Jude Children’s Research Hospital and University of London, this project led by principal investigator Dr. David Ellison is a comprehensive study of grade II LGGs with a view to deriving a molecular diagnostic/stratification system and identifying novel markers for the development of targeted therapies.

• Principal Investigator Dr. David Ellison, St. Jude Children’s Research Hospital

Molecular JPA Study

This study by Dr. KK Wong at MD Anderson Cancer Center 1) analyzes the gene expression profiles in 40-60 cases of subtotally resected JPAs located at the midline region to test whether midline located JPA also forms two subgroups with one group more aggressive, and (2) identifies prognostic markers that can predict the likelihood of progression in subtotally resected JPAs using statistical methods.

• Principal Investigator Dr. KK Wong, MD Anderson Cancer Center

Long Term Clinical Implications of PLGG Molecular Subgroups

Pediatric low grade gliomas possess the dichotomy of excellent (greater than 90%) short term overall survival with very low (less than 40%) progression-free survival leading to the following major clinical challenges: Multiple recurrences resulting in accumulation of toxic therapies, significant but extremely variable long term morbidity resulting in late mortality, and multiple pathological subgroups lumped together resulting in lack of specific and targeted therapies. In this project, in order to address these issues, Dr. Uri Tabori and colleagues at Sick Kids of Toronto hypothesize that uncovering RAS/MAPK alterations in all PLGG subtypes as well as secondary events in these cancers will enable novel molecular risk stratification of PLGG. This novel classification will guide current and future targeted therapies which are becoming available for these tumors.

• Principal Investigators Dr. Uri Tabori, Sick Kids of Toronto

Identification of the Molecular Signature of Progressive JPA

Pilocytic astrocytomas (PA), the most common childhood brain tumor, is classified into 2 groups: those that are resected and do not recur (non-progressors), and those that recur early and need further treatment, progressors. There is little that distinguishes these patients at diagnosis, a fact which leads to uncertainty regarding the need for further treatment on the part of the physician and uneasiness and worry about the long-term outcome for their children on the part of the parent.

• Principal Investigators Elizabeth Maher, MD, PhD