Faculty Research Labs

Corson Lab

Under the direction of Tim Corson, PhD, Merrill Grayson Senior Associate Professor of Ophthalmology at the IU School of Medicine and Director of Basic and Translational Research at the Eugene and Marilyn Glick Eye Institute, the Corson Lab applies chemical biology to problems in vision science. The lab uses a wide variety of techniques, including high-throughput compound screening, novel compound development, and biochemical approaches to compound mechanism of action as well as more traditional techniques, including tissue culture, expression analyses, in vivo modeling, and molecular biology.

The Corson Lab research team is developing small molecules as probes and therapeutic leads for the common, blinding afflictions of wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity–all of which are associated with abnormal excess blood vessel growth in the eye (neovascularization). The team is also investigating the basic biology of, and potential therapeutic approaches for, the pediatric ocular tumor retinoblastoma, which is responsible for one percent of childhood cancer deaths and five percent of childhood blindness.

Active Research

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 NEI R01-funded 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. With this 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.

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.

Research Team

Led by Tim Corson, PhD, the research team of the Corson Lab includes Kamakshi Sishtla (lab manager), Dr. Sheik Pran Babu Sardar Pasha (postdoctoral appointee), Trupti Shetty (PhD candidate), Bomina Park (PhD candidate), Dr. Nathan Lambert-Cheatham (research fellow), Neeta Patwari (medical student), and Maria Witcher (undergraduate student).

Protocols

Protocols

Corson Lab protocols represent research best practices and offer tactical tips.
Publications

Publications

Research findings of the Corson Lab are published in national medical science publications.