Research

Finding novel cancer genes with unbiased genome-scale screens: Systematic co-essentiality analysis to identify new non-oncogenes

A ubiquitination cascade regulating the integrated stress response and survival in carcinomas

We have employed systematic functional approaches to identify genes whose expression or function is required in specific contexts. In particular, this approach provides us with the ability to find genes that are essential in cancers, but that are not mutated nor oncogenes, which can be otherwise challenging to identify and study. Using gene essentiality measurements in 1,086 cancer cell lines to systematically identify selective co-essentiality modules, we found a new ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4, which is required for the survival of a subset of epithelial tumors. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization and upregulation of the heme-regulated inhibitor (HRI), a direct target of the complex. This is a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This work provides a novel insight on the regulation of the ISR and exposes a therapeutic opportunity to selectively eliminate dependent cancer cells (Cervia et al., Cancer Discovery, 2023).

For more information please visit: Hahn Lab Website

Enhancement of electrotransfection efficiency through understanding of underlying biological mechanisms

I design solutions to improve methods of gene delivery. Gene therapy has great potential to transform the treatment of many diseases, but there is a great need for more efficient and safe methods of gene delivery. I work at both uncovering the mechanisms by which non-viral methods of gene delivery introduce DNA to the cell and utilizing these mechanisms to develop strategies that improve efficiency, such that these methods of delivery can be more widely implemented for clinical applications. 

For more information please visit: Yuan Lab Website