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proteins destabilization of WASF3 complex and suppression of invasion.

WASF3 function is regulated by the WASF3 regulator complex (WRC), which includes the CYFIP1 and NCKAP1 proteins. Genetic knockdown of either of these proteins leads to destabilization of WASF3 complex and suppression of invasion. In collaboration with Dr. Eileen Kennedy at the University of Georgia, a novel approach to suppress WASF3 function has been developed (Cancer Res. 2016, 76(4):965-73). “Stapled peptides” are locked in an alpha helical conformation through modified amino acids, which confers drug-like properties such as high-level cellular uptake, increased stability and high specificity for intracellular targets once considered undruggable. Stapled peptides were designed to disrupt the interaction between protein surfaces of the WASF3-CYFIP1 complex. These stapled peptides lead to suppression of WASF3 activation in vitro, which leads to suppression of invasion. This data provides a proof-ofprinciple that targeting this particular protein-protein interaction could be developed into an antimetastasis therapy. Professor Georgia Cancer Coalition Distinguished Scientist Page 25 Molecular Oncology & Biomarkers Co-Leader, Thoracic Oncology Program Zhonglin Hao, MD, PhD Associate Professor Research in the Hao Laboratory focuses on combining small molecule inhibitors that effectively attack the hallmarks of cancer. Following their report that the Plk1 inhibitor volasertib synergizes with another small molecule inhibitor (YM155) in killing non-small cell lung cancer cells, volasertib showed promise in improving progression-free survival of acute myeloid leukemia patients when used in combination with cytarabine. This regimen was used for patients who were not candidates for standard induction chemotherapy (Onco Targets Ther. 2015, 8:1-11). In addition to its well-known role in cell cycle regulation, Plk1 has now been shown to be a critical regulator of cancer cell metabolism. The Hao Laboratory’s investigation of YM155’s mechanism of action has shown that YM155 is not a survivin inhibitor and that it induces cell cycle arrest in G1. It was shown that YM155 is neither a DNA chelating agent nor a topoisomerase inhibitor. YM155 causes DNA damage, which cells repair poorly, suggesting the DNA damage is a result of defective DNA repair. In collaboration with Dr. Jin Xie of University of Georgia, Department of Chemistry, the Hao Laboratory successfully engineered a nanoparticle that was able to overcome the shallow penetrance of conventional photodynamic therapy for use in the treatment of cancers residing deep within tissues (Nano Lett. 2015, 15(4):2249-56). In this approach, a SiO2 nanoparticle core was engineered to convert the X-ray energy to a spectrum of light that can further pass the energy to neighboring photosensitizer molecules and trigger photodynamic therapy. The delivery of the nanoparticle was guided by an EGFR antibody preferentially overexpressed by the cancer cells. Due to th