"My research focuses on the most lethal type of pediatric brain tumors. I’m exploring whether fast-growing tumor cells can be made to ‘differentiate’ and behave more like normal brain cells. Accomplishing this in the laboratory will be a major step toward the development of new treatments for this disease. Support from the Sontag Foundation will be critical in bringing this work to fruition, and I’m proud to be a recipient of the Distinguished Scientist Award.”
- Dr. Mariella Filbin
- Co-Director for Research, Pediatric Neurooncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, MA
- Assistant Professor, Dept. of Pediatrics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
- Associate Member, Broad Institute of Harvard and MIT, Boston, MA
About DSA-Funded Research
Brain tumors are the number one cause of cancer-related death in children. High-grade gliomas of the brain stem (called Diffuse Intrinsic Pontine Glioma or DIPG) are the most lethal pediatric brain tumors: Most children with DIPG succumb to their disease within a year of diagnosis. Within a child’s developing brain, rapidly dividing “stem cells” exit the cell cycle and differentiate into non-replicating neurons and glia. In preliminary studies, I applied a technique called single cell RNA-sequencing to thousands of individual DIPG cells. My studies showed that DIPGs are mostly composed of quickly dividing cells that resemble normal replicating stem cells. However, I also discovered that some DIPG cells are able to differentiate towards normal brain cells. These cells stop dividing and lose their potential to form new tumors despite having the same mutations as immature, dividing DIPG cells. This observation suggests that differentiation therapy, which has been successful in treating other cancers like acute promyelocytic leukemia, would work in DIPG and lead to better responses than current cytotoxic chemotherapy regimens with limited benefit. To test this hypothesis, I will use CRISPR-gene editing and chemical approaches to ablate specific genes and pathways that I have identified as potential antagonists of the developmental program and aberrant chromatin state in DIPG. I predict that ablation and inhibition of these genes and pathways will lead to cell cycle exit, growth arrest and differentiation of DIPG cells. My study plan may identify novel targets for DIPG drug development and lay the foundation for new treatment strategies in this deadly disease.
"Given Dr. Filbin’s success to date, her passion and dedication to pediatric neuro-oncology and research, I absolutely believe that she is a translational research superstar and an investigator who will make a transformative impact on childhood brain cancer. I cannot imagine a better qualified applicant and am convinced that the breadth of her contributions will continue to expand—not only through the highly promising work detailed in her proposal, but in many other yet unforeseen ways—since she is exceptionally well-trained and has great sense of dedication to conquering pediatric brain cancers."
Dr. Todd R. Golub
"Mariella has a brilliant mind. She is also driven and dedicated. Mariella is creative - but solid - and productive, yet careful. Her potential to make a difference in the lives of children with brain cancer is boundless."
Dr. Charles D. Stiles
Dana-Farber/Harvard Medical School