Dr. Maura McGrail: Iowa State University assistant professor in genetics, development and cell biology with expertise in cancer genetics and genomics in zebrafish
Title: Investigating RB transcriptional regulation in zebrafish neural development and brain tumor suppression
Abstract: Research in the McGrail lab investigates how disruption of tumor suppressor genes leads to uncontrolled cellular proliferation and cancer. We use genome engineering and classical genetics in zebrafish to model human brain cancer caused by inactivation of the tumor suppressor RB. Somatic inactivation of RB in zebrafish induces brain tumors in adults that resemble human primitive neuroectodermal tumors, a poorly differentiated and highly proliferative cancer. Transcriptome analysis of the zebrafish RB mutant brain tumors identified altered expression of transcriptional regulators, including repressive chromatin remodelers and neurogenic transcription factors. This suggests epigenetic mechanisms controlling transcriptional regulation maintain the tumor cell in a progenitor-like state. Our current projects examine how RB cooperates with chromatin remodelers to regulate gene expression during normal brain development and tumor suppression. CRISPR/Cas9 somatic gene targeting and live embryo imaging demonstrate a requirement for RB and candidate cooperators in neurogenesis. These studies reveal distinct roles for RB and chromatin remodelers in neural progenitor proliferation and survival. In conjunction, we are developing new tools to enhance precision gene editing for functional genomic studies in zebrafish. CRISPR/Cas9 targeted integration is being used to modify genes for conditional inactivation and restoration in specific neural cell populations. Through these studies we hope to increase understanding of the mechanisms driving pathogenesis in brain tumors and other RB defective cancers.
Host: Jo Anne Powell-Coffman