Corson Lab

Under the direction of Tim Corson, PhD, associate professor of ophthalmology at the IU School of Medicine and interim 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), Sardar Sheik Pran Babu (postdoctoral appointee), Trupti Shetty (PhD candidate), Bomina Park (PhD student), Darcy White (medical student), Christian Briggs (medical student) and Ivette Muzquiz (undergraduate student).

Publications

Basavarajappa HD, Sulaiman RS, Qi X, Shetty T, Pran Babu SS, Sishtla KL, Lee B, Quigley J, Alkhairy S, Briggs CM, Gupta K, Tang B, Shadmand M, Grant MB, Boulton ME, Seo SY, Corson TW. 2017. Ferrochelatase is a therapeutic target for ocular neovascularization. EMBO Molecular Medicine, e201606561. Full Text.

Lee H, Yuan Y, Rhee I, Corson TW, Seo SY. 2016. Synthesis of natural homoisoflavonoids having either 5,7-dihydroxy-6-methoxy or 7-hydroxy-5,6-dimethoxy groups. Molecules, 21, 1058. Full Text.

Lee B, Sun W, Lee H, Basavarajappa HD, Sulaiman RS, Sishtla K, Fei X, Corson TW, Seo SY. 2016. Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids. Bioorganic & Medicinal Chemistry Letters, 26, 4277–4281. Full Text.

Racher H, Soliman S, Argiropoulos B, Chan HSL, Gallie BL, Perrier R, Matevski D, Rushlow D, Piovesan B, Shaikh F, MacDonald H, Corson TW. 2016. Molecular analysis distinguishes metastatic disease from second cancers in patients with retinoblastoma. Cancer Genetics, 209, 359–363. Full Text.

O’Hare MN, Shadmand M, Sulaiman RS, Sishtla K, Sakisaka T, Corson TW. 2016. Kif14 overexpression accelerates murine retinoblastoma development. International Journal of Cancer, 139, 1752–1758. Full Text.

Sulaiman RS, Merrigan S, Quigley J, Boulton ME, Kennedy B, Seo SY, Corson TW. 2016. A small molecule pharmacotherapy ameliorates ocular neovascularization without toxicity. Scientific Reports, 6, 25509. Full Text.

Dimaras H, Corson TW. 2016. The molecular genetics of retinoblastoma. Reviews in Cell Biology and Molecular Medicine, 2, 105–142. Full Text.

Dimaras H, Corson TW, Cobrinik D, White A, Zhao J, Munier FL, Abramson DH, Shields CL, Chantada GL, Njuguna F, Gallie BL. 2015. Retinoblastoma. Nature Reviews Disease Primers, Article number: 15021, doi:10.1038/nrdp.2015.21. Full Text.

Basavarajappa HD*, Lee B*, Lee H, Sulaiman RS, An H, Magaña C, Shadmand M, Vayl A, Rajashekhar G, Kim E-Y, Suh Y-G, Lee K, Seo S-Y*, Corson TW*. 2015. Synthesis and biological evaluation of novel homoisoflavonoids for retinal neovascularization. Journal of Medicinal Chemistry, 58, 5015–5027. *equal contributors. Full Text.

Sulaiman RS, Quigley J, Qi X, O’Hare MN, Grant MB, Boulton ME, Corson TW. 2015. A simple optical coherence tomography quantification method for choroidal neovascularization. Journal of Ocular Pharmacology and Therapeutics, 31, 447–54. Full Text.

Hill JA, Lee SY, Njambi L, Corson TW, Dimaras H. 2015. Cancer genetics education in a low- to middle-income country: Evaluation of an interactive workshop for clinicians in Kenya. PLoS ONE, 10, e0129852. Full Text.

Wenzel AA, O’Hare MN, Shadmand M, Corson TW. 2015. Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma. Molecular Vision, 21, 515–522. Full Text.

Sulaiman RS, Basavarajappa HD, Corson TW. 2014. Natural product inhibitors of ocular angiogenesis. Experimental Eye Research, 129, 161–171. Full Text.

Lee B, Basavarajappa HD, Sulaiman RS, Fei X, Seo S-Y*, Corson TW*. 2014. First synthesis of the antiangiogenic homoisoflavanone, cremastranone. , 12, 7673–7677. *equal contributors. Full Text.

Luo N, Conwell MD, Chen X, Cantor LB, Wells CD, Kettenhofen CI, Westfall CJ, Weinreb RN, Corson TW, Spandau DF, Gattone VG, Iomini C, Obukhov AG, Sun Y. 2014. Primary cilia signaling mediates intraocular pressure sensation. Proceedings of the National Academy of Sciences of the USA, 111, 12871–12876. Full Text.

Corson TW, Samuels BC, Wenzel AA, Geary AJ, Riley AA, McCarthy BP, Hanenberg H, Bailey BJ, Rogers PI, Pollok KE, Rajashekhar G, Territo PR. 2014. Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development. PLoS ONE, 9, e99036. Full Text.

Singel SM, Cornelius C, Zaganjor E, Batten K, Sarode VR, Buckley DL, Peng Y, John GB, Li HC, Sadeghi N, Wright WE, Lum L, Corson TW, Shay JW. 2014. KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer. Neoplasia, 16, 247–256. Full Text.

Basavarajappa HD*, Lee B*, Fei X, Lim D, Callaghan B, Mund JA, Case J, Rajashekhar G, Seo SY*, Corson TW*. 2014. Synthesis and mechanistic studies of a novel homoisoflavanone inhibitor of endothelial cell growth. PLoS ONE, 9, e95694. *equal contributors. Full Text.

Thériault BL, Basavarajappa HD, Lim H, Pajovic S, Gallie BL*, Corson TW*. 2014. Transcriptional and epigenetic regulation of KIF14 overexpression in ovarian cancer. PLoS ONE, 9, e91540. *equal contributors. Full Text.

Thériault BL, Dimaras H, Gallie BL, Corson TW. 2014. The genomic landscape of retinoblastoma: a review. Clinical and Experimental Ophthalmology, 42, 33–52. Full Text.

Hines J, Gough JD, Corson TW, Crews CM. 2013. Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proceedings of the National Academy of Sciences of the USA, 110, 8942–8947. Full Text.

Rushlow DE, Mol BM, Kennett JY, Yee S, Pajovic S, Thériault BL, Prigoda-Lee NL, Spencer C, Dimaras H, Corson TW, Pang R, Massey C, Godbout R, Jiang Z, Zacksenhaus E, Paton K, Moll AC, Houdayer C, Raizis A, Halliday W, Lam WL, Boutros PC, Lohmann D, Dorsman JC, Gallie BL. 2013. Characterization of retinoblastoma tumours without RB1 mutations: genomic, gene expression and clinical studies. Lancet Oncology, 14, 327–334. Full Text.

Thériault BL & Corson TW. 2012. KIF14 (kinesin family member 14). Atlas of Genetics & Cytogenetics in Oncology & Haematology, 16, 695–699. Full Text.

Basavarajappa HD, Corson TW. 2012. KIF14 as an oncogene in retinoblastoma: a target for novel therapeutics? Future Medicinal Chemistry, 4, 2149–52. Full Text.

Temming P, Corson TW, Lohmann D. 2012. Retinoblastoma tumorigenesis: genetic and epigenetic changes walk hand in hand. Future Oncology, 8, 525–528. Full Text.

Shah AS, Ramasubramanian A, Corson TW. 2012. Prenatal diagnosis & genetics. In Retinoblastoma, ed. Ramasubramanian A, Shields CL. New Delhi: Jaypee Brothers Medical Publisher. Purchase.

Corson TW, Pajovic S, Dimaras H, Thériault BL, Gallie BL. 2012. Author response: Does the time of inactivation of pRb determine the cell of origin of retinoblastoma? Investigative Ophthalmolology & Visual Science, 53:676. Full Text.

Pajovic S*, Corson TW*, Spencer C, Dimaras H, Orlic-Milacic M, Marchong MN, To KH, Thériault B, Auspitz M, Gallie BL. 2011. The TAg-RB murine retinoblastoma cell of origin has immunohistochemical features of differentiated Müller glia with progenitor properties. Investigative Ophthalmolology & Visual Science, 52:7618–7624. *equal contributors.

Neklesa TK*, Tae HS*, Schneekloth AR, Stulberg, MJ, Corson TW, Sundberg TB, Raina K, Holley SS & Crews CM. 2011. Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nature Chemical Biology, 7:538–543. *equal contributors. Full Text.

Corson TW, Cavga H, Aberle N & Crews CM. 2011. Triptolide directly inhibits dCTP pyrophosphatase. ChemBioChem, 12:1767–1773. Corresponding author. Full Text.

Uemura T, Green M, Corson TW, Perova T, Li PP & Warsh JJ. 2011. Bcl-2 SNP rs956572 associates with disrupted intracellular calcium homeostasis in bipolar I disorder. Bipolar Disorders, 13:41–51. Full Text.

Buckley DL, Corson TW, Aberle N & Crews CM. 2011. HIV protease-mediated activation of sterically capped proteasome inhibitors and substrates. Journal of the American Chemical Society, 133:698–700. Full Text.

Corson TW. 2010. Medichem — BIT Life Sciences’ First Annual International Conference. IDrugs13:453–456.

Corson TW*, Aberle N* & Crews CM. 2008. Design and applications of bifunctional small molecules: why two heads are better than one. ACS Chemical Biology 3:677–692. *equal contributors. Full Text.

Dimaras H, Khetan V, Halliday W, Orlic M, Prigoda NL, Piovesan B, Marrano P, Corson TW, Prigoda N, Piovesan B, Eagle RC Jr, Squire JA & Gallie BL. 2008. Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma. Human Molecular Genetics, 17:1363–1372. Full Text.

Huang JC*, Babak T*, Corson TW, Chua G, Khan S, Gallie BL, Hughes TR, Blencowe BJ, Frey BJ & Morris QD. 2007. Using expression profiling data to identify human microRNA targets. Nature Methods, 4:1045-1049.*equal contributors. Full Text.

Corson TW & Crews CM. 2007. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell, 130:769-774.

Madhavan J, Coral K, Mallikarjuna K, Corson TW, Amit N, Khetan V, George R, Biswas J, Gallie BL & Kumaramanickavel G. 2007. High expression of KIF14 in retinoblastoma: association with older age at diagnosis. Investigative Ophthalmology & Visual Science, 48:4901-4906. Full Text.

Corson TW, Zhu CQ, Lau S, Shepherd FA, Tsao M-S & Gallie BL. 2007. KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer. Clinical Cancer Research, 13:3229-3234. Full Text.

Corson TW & Gallie BL. 2007. One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes, Chromosomes and Cancer, 46:617-634. Full Text.

Bowles E*, Corson TW*, Bayani J, Squire JA, Wong N, Lai PB-S & Gallie BL. 2007. Profiling genomic copy number changes in retinoblastoma beyond loss of RB1. Genes, Chromosomes and Cancer 46:118-129. *equal contributors. Full Text.

Corson TW & Gallie BL. 2006. KIF14 mRNA expression is a predictor of grade and outcome in breast cancer. International Journal of Cancer 119:1088-1094. Full Text.

Spencer C, Pajovic S, Devlin H, Dinh Q-D, Corson TW & Gallie BL. 2005. Distinct patterns of expression of the RB gene family in mouse and human retina. Gene Expression Patterns 5:687-694. Full Text.

Corson TW, Huang A, Tsao M-S & Gallie BL. 2005. KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers. Oncogene 24:4741-4753. Full Text.

Marchong MN, Chen D, Corson TW, Lee C, Harmandayan M, Bowles E, Chen N & Gallie BL. 2004. Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. Molecular Cancer Research 2:495-503. Full Text.

Wasserman MJ, Corson TW, Li PP, Sibony D, Pennefather P & Warsh JJ. 2004. Chronic lithium treatment attenuates intracellular calcium mobilization. Neuropsychopharmacology 29:759-769. Full Text.

Corson TW, Woo KK, Li PP & Warsh JJ. 2004. Cell-type specific regulation of calreticulin and Bcl-2 expression by mood stabilizer drugs. European Neuropsychopharmacology 14:143-150. Full Text.

Corson TW, Li PP, Kennedy JL, Macciardi F, Cooke RG, Parikh SV & Warsh JJ. 2001. Association analysis of G-protein β3 subunit gene in bipolar disorder. Molecular Psychiatry 6:125-126.

Protocols

Corson Lab protocols range from the routine to the esoteric best practices and tips. External research labs are invited to both use and share these protocols, with appropriate attribution to the Corson Lab at IU School of Medicine.

Routine Cell Culture

Routine Cell Culture

Guidelines and general procedures are offered for culturing, subculturing and freezing adherent cells within a traditional lab setting.
Culture Cell Tips

Culture Cell Tips

In order to avoid culture contamination for optimal results, follow these best practices.
Bis-Tris Gel Recipes

Bis-Tris Gel Recipes

Explore handy recipes for bis-tris polyacrylamide gels designed for optimal separation of a wide range of proteins.
SDS-PAGE and Immunoblotting

SDS-PAGE and Immunoblotting

Determine characteristics of protein antigens within complex mixtures using Laemmli and bis-tris protocols.
Soft Agar Colony Assay

Soft Agar Colony Assay

Confirm cellular anchorage-independent growth using the soft agar colony assay method.
Whole-Cell Pulldown Protocol

Whole-Cell Pulldown Protocol

Consider an alternative method to whole-cell pulldown that involves cell fractionation using biotinylated affinity reagents.
Silver Staining

Silver Staining

Best practices are outlined to achieve optimal results for mass spectrometry compatible silver staining.
Precautions for Working with RNA

Precautions for Working with RNA

Due to its liable nature within the lab, simple precautions will reduce the degradation of RNA samples.
Publication for Powerpoint

Publication for Powerpoint

Simple instructions are provided to enhance high-resolution graphic files for PowerPoint presentations.