Amanda Muhs Saratsis
CBTN Samples Used
Northwestern University Clinical and Translational Sciences Institute (NUCATS)
The Ann & Robert H. Lurie Faculty Practice Plan
The Frankel Foundation
The Pediatric Cancer Research Foundation
The goal of this project is to determine patterns of tumor-specific protein expression in tumor tissue and cerebrospinal fluid (CSF) collected from children with glioma and normal controls using novel proteomics techniques. Expression patterns of specific proteins known as Histones will be correlated with patterns of gene expression (RNA-Seq) that contribute to tumor formation in order to determine their utility as clinical biomarkers of disease and response to therapy.
What are the goals of this project?
The goal of this project is identify isoforms of Histone proteins that contribute to tumor formation and reflect treatment response.
What is the impact of this project?
We hypothesize that these tumor epigenetic signatures may not only serve as clinically accessible biomarkers of disease for diagnosis and molecular characterization, but will also provide insight to the mechanism of tumor formation for improved treatment. Specifically, identified epigenetic signatures will implicate activity of specific histone modifying enzymes that alter chromatin structure and function to result in tumorigeneic gene expression patterns, revealing candidate genes and histone modifying enzymes for testing as potential therapeutic targets in future research. This research therefore has the potential to improve clinical outcomes for children with glioma by facilitating safer clinical diagnosis, informing stratification to specific and more effective therapeutic agents, and enabling monitoring of treatment response, all by using clinically accessible CSF specimens in lieu of tumor tissue.
Why the CBTN request is important to this project?
Matched CSF and tumor tissue specimens are required to conduct the proposed research. The CBTN contains this precious resource from children with low grade, high grade and diffuse intrinsic pontine glioma, with multiple collection events in some instances. In addition, the CBTN is in the process of acquiring whole exome and transcriptome (RNA-Seq) data on a large cohort of their banked glioma specimens. We are requesting paired CSF and fresh glioma tumor tissue for proteomics and ChIP-Seq, and will integrate these results with Nantomics RNA-Seq data (where available) for these specimens.
The Children's Brain Tumor Network contributed to this project by providing cerebral spinal fluid and tissue samples.
Shejuan An, Research Technician and Data Analyst
Tina Huang, Research Technician, Bioinformatician
Jin Qi, Research Technician
Amanda Muhs Saratsis, MD
Dr. Saratsis has clinical appointments in the Departments of Neurological Surgery at Northwestern Memorial and Lurie Children's Hospitals, caring for children and adults with congenital disorders of the central nervous system. Dr. Saratsis has expertise in the clinical management and molecul
Ann & Robert H. Lurie Children’s Hospital of Chicago
High-grade glioma/astrocytoma (WHO grade III/IV)
High-grade Gliomas (HGG) in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric specific HGG preclinical models. These models are needed to help test the effective
Brainstem glioma- Diffuse intrinsic pontine glioma
A presumptive diagnosis of DIPG based on classic imaging features, in the absence of a histologic diagnosis, has been routinely employed. Increasingly however, histologic confirmation is obtained for both entry into research studies and molecular characterization of the tumor.[