The overarching theme of Paula’s research group is the development of novel and selective anticancer agents. A major focus in her laboratory is the use of DNA aptamers (protein-binding oligonucleotides) for cancer therapy. In particular, she was involved in the discovery and bench-to-bedside translation of a G-rich DNA aptamer named AS1411 (now ACT-GRO-777, previously AGRO100), which became the first anticancer aptamer to be tested in human clinical trials. AS1411 folds into a G-quadruplex structure that binds to nucleolin (a protein present at high levels on the surface of cancer cells) and can kill cancer cells without harming non-malignant cells. Ongoing basic research related to AS1411 aims to better understand the molecular mechanisms responsible for its cancer-selective effects and unusual ability to get inside cells. AS1411 has also been widely used around the world as a tool to investigate the biological functions of nucleolin and as a cancer-targeting ligand to deliver diverse attached cargoes selectively to tumors. Currently, the group is developing various AS1411-linked nanoparticles for use in cancer therapy, drug delivery, and imaging. Other recent projects in Paula’s laboratory have focused on the activity and mechanism of various synthetic and plant-derived small molecules with antiproliferative effects. Of these, a small molecule named XB05 is of particular interest because of its potential for translation to the clinic: XB05-like molecules have cancer-selective cytotoxicity, a novel mechanism of action (disruption of redox homeostasis), proven in vivo efficacy with no acute toxicity in mouse models, and an associated candidate biomarker that predicts cancer cell response to XB05. In addition to pursuing basic and translational research, Paula is interested in developing programs to increase research commercialization and entrepreneurship in academia.