Sadie Allen

Sadie Allen

Biography

Sadie Allen is a rising sophomore at North Carolina Central University majoring in Biomedical Sciences pursuing minors in Public Health Education and Political Science. Sadie is an honors student on the pre-medical track with interests in internal medicine and health policy-relevant research. This summer, Sadie is interning at the Whitehead Institute for Biomedical Research under Dr. Richard Young and is exploring the function of oncogenic fusion transcription factors and their role in tumorigenesis. Sadie believes in an interdisciplinary approach to problem solving due to her early exposure to health equity research and engineering design. She has unique perspectives on health disparities and chronic disease due to her proximity to communities that have long suffered from them and is actively seeking opportunities to expand her knowledge on the intersection of medicine, research, and health policy. Sadie’s career goals include obtaining her MD/PhD in Health Policy and dividing her time between patients, academic research, and health policy analysis.

Abstract

QFusion Transcription Factors Drive Oncogenesis through Hypertranscription

Fusion transcription factors (TFs) are drivers of aggressive cancers. While most cancers arise through multiple genetic events, fusion TF-driven cancers are initiated by a single event, leaving a mystery as to how fusion TFs drive oncogenesis. The prevailing model posits that the oncogenic potential of fusion TFs stems from their regulation of a subset of genes determined by their DNA-binding domain. However, this does not fully explain how these cancers meet the demands of sustained proliferation. Notably absent from this model is hypertranscription, the process by which oncogenic TFs amplify global transcription by occupying sites of active transcription, driving high RNA output to sustain constant proliferation. As this model of oncogenesis is diametrically opposed to the current view of fusion TF function, we challenge the prevailing model. We hypothesize that fusion TFs directly induce hypertranscription. To test this, we engineered Ewing sarcoma cells with tunable EWS::FLI expression. Using ChIP-seq and RNA-seq, we will assess genome-wide EWS::FLI binding and corresponding RNA levels. We expect EWS::FLI to occupy most active promoters and drive elevated expression of associated transcripts upon induction. These findings would challenge the current paradigm and support a broader role for fusion TFs in reprogramming global transcription.