Corson Lab

Under the direction of Tim Corson, PhD, associate professor of ophthalmology at IU School of Medicine, the Corson Lab applies chemical biology to problems in vision science using a wide variety of techniques, including high-throughput compound screening, phage display and biochemical approaches to compound mechanism of action. The lab also applies more traditional techniques, including tissue culture, expression analyses, protein purification and molecular biology. The Corson Lab research team is developing small molecules as probes and therapeutic leads for the common afflictions of age-related macular degeneration and retinopathy of prematurity, both of which are associated with abnormal excess blood vessel growth (neovascularization). The team is 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. In addition, the lab seeks novel, targeted therapeutic approaches for most common intraocular malignancy in adults, uveal melanoma.

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 Sulcie 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 compounds in various angiogenesis models, the Corson Lab is interested in discovering how these compounds work at the molecular level and is pursuing other targets using biochemical techniques previously developed by Dr. Corson while working at Yale University. With different targets in hand, the Corson Lab research team will be better able to understand now only how these molecules work, but how else they may target the same system pharmacologically.

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. Recently, in collaboration with Drs. Brenda Gallie and Brigitte Thériault of the University of Toronto, the Corson Lab helped to identify transcription factors and microRNAs that might help drive KIF14 overexpression in ovarian cancer; however, questions remain: (1) How does KIF14 promote growth? and (2) Can KIF14 function be disrupted as a novel targeted therapeutic approach? The Corson Lab at IU School of Medicine seeks to address these questions and develop the tools to do so, 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 Babu (Postdoctoral), Trupti Shetty (PhD Candidate), Bomina Park (PhD Student), Darcy White (Medical Student), Christian Briggs (Medical Student), and Sarah Klotz (Undergraduate Student).

Publications

Access to the full text of some publications may require journal subscriptions. For recent publications, open-access accepted versions of manuscripts are available at IUPUI ScholarWorks.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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

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.

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.

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

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

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

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.