Epigenetic Regulation of MYC in Pediatric Cancer: Investigating the Role of Ancestral Repetitive Elements and Nuclear Positioning
Cancer is the leading cause of disease-related death among American children. Despite significant progress in recent decades, which has provided the possibility of a cure for many diagnosed children, we have not succeeded in improving the prognosis for certain cancer subtypes that have seen no advancement in the last 50 years. A key player in many of these aggressive subtypes is a gene called MYC. When MYC becomes overactive, it can cause cells to grow and divide uncontrollably, as well as evade the body's natural anti-cancer mechanisms. Targeting and taming MYC activity has proven challenging, making it one of the holy grails of cancer therapy development. Intriguingly, in some childhood cancers, one copy of the MYC gene is turned off, while the other copy becomes overactive. We don't fully understand why this happens or how it works, but the prospect of identifying a natural mechanism to turn off MYC in cancer cells is very exciting to us.
Project Goals
Our goal is to investigate a so-far undescribed, natural mechanism that turns off the MYC gene in several childhood cancers. We believe this mechanism works by physically moving the MYC gene to specific areas within the cell that prevent its activation. Intriguingly, parts of our DNA that do not contain genes and were until recently considered "junk" may actually serve as literal anchors, guiding MYC to these inactive regions. Using cutting-edge microscopy and sequencing techniques, we aim to unravel this novel mechanism and identify the crucial DNA elements and proteins that control MYC's movement in cancer cells. We believe that these insights will advance our understanding of how cancer-driving genes are not only activated but also inactivated. At the same time, these insights could potentially allow us to hijack this mechanism, artificially repositioning MYC in cancer cells to switch it off. This approach may lead to more effective and less toxic treatments for aggressive childhood cancers, ultimately improving the lives of young patients and their families.
