We plan to identify genes that are up- and down-regulated in brain tumors compared to normal tissue samples and genes that are up- and down-regulated in brain tumors with different mutations. We will compare these patient-derived gene expression profiles to data we have generated using human brain cancer cells grown in the lab that have either been genetically manipulated, or treated with various drugs.
What are the goals of this project?
The goals of this project are to identify genes that are differentially expressed in pediatric brain tumors compared to normal tissue, to identify genes that are differentially expressed in brain tumors with different mutations (eg. tumors with wild type histones compared to H3.3/H3.1 K27M and H3.3 G34R/V mutant tumors), and to compare the above gene signatures to RNAseq data that we have generated in our lab using cultured human brain cancer lines, which have been either genetically manipulated or treated with various small molecule inhibitors to target different chromatin and epigenetic regulators.
What is the impact of this project?
By analyzing and comparing patient and laboratory datasets we hope to identify gene expression patterns characteristic of different subsets of pediatric brain tumors, and to investigate the potential consequences of our genetic manipulation and drug treatment studies, which could provide a theoretical basis for the development of new therapies.
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.
- Dr. Jay Kalin from Johns Hopkins
- Dr. Federica Piccioni of the Genetic Perturbations Platform group at the Broad Institute
Mariella Filbin, MD, PhD
Dr. Mariella Filbin is the Research Co-Director at Harvard Medical School. She received her MD and PhD in biochemistry and molecular biology from the Medical University of Graz, Austria. Following graduation she completed her pediatric residency at the Boston Children's Hospital and complete
Philip Cole, MD, PhD
Dr. Phil Cole is a Professor of Medicine and Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He received his MD and PhD from Johns Hopkins where he pursued research in bioorganiz chemistry. Following graduation he completed post-doctoral training at Harvard Medical Scho
David Root, PhD
Dr. David Root is the Senior Director of the Genetic Perturbation Platform and Functional Genomics Consortium at the Broad Institute of MIT and Harvard. He received his PhD in physical chemistry from Stanford University. He was previously assistant professor of physical chemistry at Swarthmore Co
Todd Golub, MD
Dr. Todd Golub is the Core Institute Member, Chief Scientific Officer, and Director of the Cancer Program at Broad Institute. He received his medical degree from the University of Chicago Pritzker School of Medicine. Following graduation, he completed his internship, residency, and fellowship tra
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.[
Gene-22. Re-Programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG
Diffuse intrinsic high grade glioma (DIPG) is an almost universally fatal tumor of childhood characterized by epigenetic dysregulation driven by somatic H3.3/H3.1 K27M mutations observed in >80% of tumors. We conducted a chromatin-focused CRISPR screen and identified a novel strategy to inhibi
Jamie Anastas, Mariella Filbin, Mirhee Kim, Jay Kalin, Barry Zee, Andres Blanco, Jayanta Das, Todd Golub, Philip Cole, Yang Shi