Characterization of Chromatin Landscapes to Identify Therapeutic Vulnerabilities in Diffuse Midline Gliomas.
Background:
DNA is the instruction book that tells a cell when to grow, divide, and develop. In adult cancers, many words in the instruction book are misspelled resulting in malignancy. While adult cancers are caused by numerous DNA errors, or mutations, that accumulate over a lifetime, pediatric cancers have few mistakes in spelling. How do pediatric cancers arise with such few DNA errors? It turns out that pediatric cancers are caused by misspaced words, not misspelled words. Unfortunately, studying word spacing, also known as epigenetics, in cancer has historically been very difficult.
Project Goal:
My research focuses on developing new, cost-effective and easy to use methods for studying word spacing, or epigenetics, in pediatric cancers. We are beginning our efforts with a study of diffuse midline gliomas, an incurable pediatric brain tumor. These tumors are caused by epigenetic dysfunction, leading to inappropriate word spacing and cancer growth despite having very few mutations. We have used our methodologies to profile epigenetic dysfunction in these cancers and have found new therapeutic strategies to restore appropriate word spacing, resulting in cancer death. With our methods, we are also poised to make breakthroughs in other pediatric cancers caused by inappropriate word spacing, including medulloblastoma, neuroblastoma, and acute myeloid leukemias.
