Corson Lab

Active Research

• Novel Antiangiogenic Compounds
  

  There is a pressing need for novel small molecule drugs to block pathological neovascularization in the eye. In collaboration with Professor Seung-Yong Seo of Gachon University and Professor Dulcie Mulholland of the University of Surrey, the Corson Lab research team are producing novel antiangiogenic compounds based on natural products. The team previously synthesized cremastranone, an antiangiogenic natural product, and developed a novel isomer for this compound with antiangiogenic activity against retinal endothelial cells. More recently, Corson Lab researchers have undertaken a structure-activity relationship study of this class of compounds and developed a new analog, SH-11037, with promising antiangiogenic activity in vitro and in vivo.

  In addition to the testing of novel compounds in various angiogenesis models, the Corson Lab is interested in discovering how these compounds work at the molecular level by using chemical proteomics approaches. Current work focuses on the heme synthesis enzyme ferrochelatase, which is a target of cremastranone, and which the Corson Lab has shown is important for angiogenesis in vitro and in vivo. They have also developed new small molecule inhibitors of this enzyme. A target of SH-11037 is the lipid modulating enzyme soluble epoxide hydrolase, also implicated in angiogenesis and an appealing therapeutic target. A further protein of interest is the redox-regulatory transcriptional activator APE1/Ref-1, which is studied for its role in angiogenesis and inflammation; a Ref-1 inhibitor is in clinical trials for eye disease. With these and other targets in hand, the Corson Lab research team will be better able to understand not only how antiangiogenic molecules work, but how else they may target the same systems pharmacologically to find new drug candidates.

• KIF14 as a Novel Oncogene
  

  During his time at the Ontario Cancer Institute at the University of Toronto, Dr. Corson identified the mitotic kinesin KIF14 as a highly overexpressed gene in a minimal common region of somatic genomic gain in retinoblastoma. In this particular form of cancer, KIF14 is increased at the DNA, mRNA and protein levels. In addition to showing that overexpression of KIF14 is not only seen in retinoblastoma, Dr. Corson noted overexpression in breast and lung tumors, in which increased expression was prognostic for poor outcome in both cancer forms.

  KIF14 is crucial for efficient cytokinesis, although its exact functions remain enigmatic. The Corson Lab research team demonstrated that siRNA-mediated knockdown of KIF14 greatly reduced the proliferation and tumorigenicity of cancer cells in vitro, suggesting its importance for the neoplastic phenotype. Others have since confirmed this in multiple cancer types. The Corson Lab was involved in collaborations to help identify transcription factors and microRNAs that might help drive KIF14 overexpression in ovarian cancer, and to help assess the role of KIF14 in chemosensitivity in triple-negative breast cancer. Recently, the Corson Lab showed that KIF14 overexpression could accelerate retinoblastoma development in vivo, providing key further evidence of this importance of this gene for cancer. The lab continues to explore this and other areas of retinoblastoma biology, including developing novel models of retinoblastoma and methods for analyzing them.