Our work utilizes the fascinating characteristics of intestinal stem cells to address fundamental questions in cell and cancer biology: How do cells identify, measure, and respond to each other and to their environment? What are the signals that control the renewal and regeneration of tissues? How do these signals go wrong in cancer? Our long-term goal is to uncover an underlying circuit theory behind these behaviors – a set of predictive principles that tell us how complex functionality arises from simpler biological components. We have a particular interest in kinase networks that regulate healthy tissue homeostasis and become damaged in cancer. Through our quantitative high-throughput imaging and drug discovery efforts, we are finding new ways to understand and repair these networks.
Curtis Thorne, PhD
Associate Professor, Cellular and Molecular Medicine
Co-Director, Graduate Program in Molecular Medicine
Associate Professor, BIO5 Institute
Research Interests:
Molecular Medicine Grad Program:
Yes
Bibliography
2023
Cantoria, M. Jo, E. Alizadeh, J. Ravi, R. P. Varghese, N. Bunnag, K. W. Pond, A. N. Kettenbach, Y. Ahmed, A. L. Paek, J. J. Tyson, et al., "Feedback in the β-catenin destruction complex imparts bistability and cellular memory.", Proc Natl Acad Sci U S A, vol. 120, issue 2, pp. e2208787120, 2023 Jan 10.
PMCID: PMC9926258 PMID: 36598937
Song, H., R. A. Sontz, M. J. Vance, J. M. Morris, S. Sheriff, S. Zhu, S. Duan, J. Zeng, E. Koeppe, R. Pandey, et al., "High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer.", JCI Insight, vol. 8, issue 13, 2023 Jul 10.
PMCID: PMC10371337 PMID: 37219942
Kassel, S., A. J. Hanson, H. Benchabane, K. Saito-Diaz, C. R. Cabel, L. Goldsmith, M. Taha, A. Kanuganti, V. H. Ng, G. Xu, et al., "USP47 deubiquitylates Groucho/TLE to promote Wnt-β-catenin signaling.", Sci Signal, vol. 16, issue 771, pp. eabn8372, 2023 Feb 07.
PMCID: PMC10038201 PMID: 36749823
Lasick, K. A., E. Jose, A. M. Samayoa, L. Shanks, K. W. Pond, C. A. Thorne, and A. L. Paek, "FOXO nuclear shuttling dynamics are stimulus-dependent and correspond with cell fate.", Mol Biol Cell, vol. 34, issue 3, pp. ar21, 2023 Mar 01.
PMCID: PMC10011729 PMID: 36735481
Mallick, S., J. Chakrabarti, J. Eschbacher, A. G. Moraitis, A. E. Greenstein, J. Churko, K. W. Pond, A. Livolsi, C. A. Thorne, A. S. Little, et al., "Genetically engineered human pituitary corticotroph tumor organoids exhibit divergent responses to glucocorticoid receptor modulators.", Transl Res, vol. 256, pp. 56-72, 2023 Jun.
PMID: 36640905
2022
Chakrabarti, J., R. Pandey, J. M. Churko, J. Eschbacher, S. Mallick, Y. Chen, B. Hermes, P. Mallick, B. N. Stansfield, K. W. Pond, et al., "Development of Human Pituitary Neuroendocrine Tumor Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.", Cells, vol. 11, issue 21, 2022 Oct 23.
PMCID: PMC9659185 PMID: 36359740
2021
Tomchaney, M., M. Contoli, J. Mayo, S. Baraldo, S. Li, C. R. Cabel, D. A. Bull, S. Lick, J. Malo, S. Knoper, et al., "Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.", BMC Pulm Med, vol. 21, issue 1, pp. 275, 2021 Aug 23.
PMCID: PMC8381712 PMID: 34425811
Grant, A., R. M. Xicola, V. Nguyen, J. Lim, C. Thorne, B. Salhia, X. Llor, N. Ellis, and M. Padi, "Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers.", Sci Rep, vol. 11, issue 1, pp. 23507, 2021 12 06.
PMCID: PMC8648784 PMID: 34873211
Wu, M-H., M. Padilla-Rodriguez, I. Blum, A. Camenisch, V. Figliuolo da Paz, M. Ollerton, J. Muller, S. Momtaz, S. A. T. Mitchell, P. Kiela, et al., "Proliferation in the developing intestine is regulated by the endosomal protein Endotubin.", Dev Biol, vol. 480, pp. 50-61, 2021 12.
PMCID: PMC8555764 PMID: 34411593
Chen, E. C., P. Gilchuk, S. J. Zost, N. Suryadevara, E. S. Winkler, C. R. Cabel, E. Binshtein, R. E. Chen, R. E. Sutton, J. Rodriguez, et al., "Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals.", Cell Rep, vol. 36, issue 8, pp. 109604, 2021 08 24.
PMCID: PMC8352653 PMID: 34411541
Perez-Miller, S., M. Patek, A. Moutal, P. Duran, C. R. Cabel, C. A. Thorne, S. K. Campos, and R. Khanna, "Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry.", ACS Chem Neurosci, vol. 12, issue 8, pp. 1299-1312, 2021 04 21.
PMCID: PMC8029449 PMID: 33787218
2020
Pond, K. W., K. Doubrovinski, and C. A. Thorne, "Wnt/β-catenin Signaling in Tissue Self-Organization.", Genes (Basel), vol. 11, issue 8, 2020 08 14.
PMCID: PMC7464740 PMID: 32823838
Sanman, L. E., I. W. Chen, J. M. Bieber, C. A. Thorne, L. F. Wu, and S. J. Altschuler, "Generation and Quantitative Imaging of Enteroid Monolayers.", Methods Mol Biol, vol. 2171, pp. 99-113, 2020.
PMID: 32705637
2019
Cabel, C. R., E. Alizadeh, D. J. Robbins, Y. Ahmed, E. Lee, and C. A. Thorne, "Single-Cell Analyses Confirm the Critical Role of LRP6 for Wnt Signaling in APC-Deficient Cells.", Dev Cell, vol. 49, issue 6, pp. 827-828, 2019 06 17.
PMCID: PMC6613640 PMID: 31211991
2018
Miyata, N., L. L. Morris, Q. Chen, C. Thorne, A. Singla, W. Zhu, M. Winter, S. D. Melton, H. Li, L. Sifuentes-Dominguez, et al., "Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation.", Cell Rep, vol. 24, issue 9, pp. 2342-2355, 2018 Aug 28.
PMCID: PMC6177233 PMID: 30157428
Thorne, C. A., I. W. Chen, L. E. Sanman, M. H. Cobb, L. F. Wu, and S. J. Altschuler, "Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization.", Dev Cell, vol. 44, issue 5, pp. 624-633.e4, 2018 03 12.
PMCID: PMC5849535 PMID: 29503158
2017
Coster, A. D., C. A. Thorne, L. F. Wu, and S. J. Altschuler, "Examining Crosstalk among Transforming Growth Factor β, Bone Morphogenetic Protein, and Wnt Pathways.", J Biol Chem, vol. 292, issue 1, pp. 244-250, 2017 Jan 06.
PMCID: PMC5217683 PMID: 27895117
Coate, K. C., G. Hernandez, C. A. Thorne, S. Sun, T. D. V. Le, K. Vale, S. A. Kliewer, and D. J. Mangelsdorf, "FGF21 Is an Exocrine Pancreas Secretagogue.", Cell Metab, vol. 25, issue 2, pp. 472-480, 2017 Feb 07.
PMCID: PMC5299054 PMID: 28089565
Li, B., D. Orton, L. R. Neitzel, L. Astudillo, C. Shen, J. Long, X. Chen, K. C. Kirkbride, T. Doundoulakis, M. L. Guerra, et al., "Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors.", Sci Signal, vol. 10, issue 485, 2017 Jun 27.
PMID: 28655862
2016
Wang, Z., O. Tacchelly-Benites, E. Yang, C. A. Thorne, H. Nojima, E. Lee, and Y. Ahmed, "Wnt/Wingless Pathway Activation Is Promoted by a Critical Threshold of Axin Maintained by the Tumor Suppressor APC and the ADP-Ribose Polymerase Tankyrase.", Genetics, vol. 203, issue 1, pp. 269-81, 2016 05.
PMCID: PMC4858779 PMID: 26975665
2015
Thorne, C. A., C. Wichaidit, A. D. Coster, B. A. Posner, L. F. Wu, and S. J. Altschuler, "GSK-3 modulates cellular responses to a broad spectrum of kinase inhibitors.", Nat Chem Biol, vol. 11, issue 1, pp. 58-63, 2015 Jan.
PMCID: PMC4270937 PMID: 25402767
Karra, A. S., C. A. Taylor, C. A. Thorne, and M. H. Cobb, "A Kinase Divided.", Cancer Cell, vol. 28, issue 2, pp. 145-7, 2015 Aug 10.
PMID: 26267529
2013
Hao, J., A. Ao, L. Zhou, C. K. Murphy, A. Y. Frist, J. J. Keel, C. A. Thorne, K. Kim, E. Lee, and C. C. Hong, "Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen.", Cell Rep, vol. 4, issue 5, pp. 898-904, 2013 Sep 12.
PMCID: PMC3923627 PMID: 24012757
Saito-Diaz, K., T. W. Chen, X. Wang, C. A. Thorne, H. A. Wallace, A. Page-McCaw, and E. Lee, "The way Wnt works: components and mechanism.", Growth Factors, vol. 31, issue 1, pp. 1-31, 2013 Feb.
PMCID: PMC3697919 PMID: 23256519
2012
Hang, B. I., C. A. Thorne, D. J. Robbins, S. S. Huppert, L. A. Lee, and E. Lee, "Screening for small molecule inhibitors of embryonic pathways: sometimes you gotta crack a few eggs.", Bioorg Med Chem, vol. 20, issue 6, pp. 1869-77, 2012 Mar 15.
PMCID: PMC3298638 PMID: 22261025
2011
Thorne, C. A., B. LaFleur, M. Lewis, A. J. Hanson, K. K. Jernigan, D. C. Weaver, K. A. Huppert, T. W. Chen, C. Wichaidit, C. S. Cselenyi, et al., "A biochemical screen for identification of small-molecule regulators of the Wnt pathway using Xenopus egg extracts.", J Biomol Screen, vol. 16, issue 9, pp. 995-1006, 2011 Oct.
PMCID: PMC3694444 PMID: 21859680
Ni, T. T., E. J. Rellinger, A. Mukherjee, S. Xie, L. Stephens, C. A. Thorne, K. Kim, J. Hu, E. Lee, L. Marnett, et al., "Discovering small molecules that promote cardiomyocyte generation by modulating Wnt signaling.", Chem Biol, vol. 18, issue 12, pp. 1658-68, 2011 Dec 23.
PMCID: PMC3645312 PMID: 22195568
2010
Jernigan, K. K., C. S. Cselenyi, C. A. Thorne, A. J. Hanson, E. Tahinci, N. Hajicek, W. M. Oldham, L. A. Lee, H. E. Hamm, J. R. Hepler, et al., "Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity.", Sci Signal, vol. 3, issue 121, pp. ra37, 2010 May 11.
PMCID: PMC3088111 PMID: 20460648
Thorne, C. A., A. J. Hanson, J. Schneider, E. Tahinci, D. Orton, C. S. Cselenyi, K. K. Jernigan, K. C. Meyers, B. I. Hang, A. G. Waterson, et al., "Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α.", Nat Chem Biol, vol. 6, issue 11, pp. 829-36, 2010 Nov.
PMCID: PMC3681608 PMID: 20890287
Alfaro, M. P., A. Vincent, S. Saraswati, C. A. Thorne, C. C. Hong, E. Lee, and P. P. Young, "sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair.", J Biol Chem, vol. 285, issue 46, pp. 35645-53, 2010 Nov 12.
PMCID: PMC2975189 PMID: 20826809
Saraswati, S., M. P. Alfaro, C. A. Thorne, J. Atkinson, E. Lee, and P. P. Young, "Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling.", PLoS One, vol. 5, issue 11, pp. e15521, 2010 Nov 29.
PMCID: PMC2993965 PMID: 21170416
2008
Cselenyi, C. S., K. K. Jernigan, E. Tahinci, C. A. Thorne, L. A. Lee, and E. Lee, "LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of beta-catenin.", Proc Natl Acad Sci U S A, vol. 105, issue 23, pp. 8032-7, 2008 Jun 10.
PMCID: PMC2430354 PMID: 18509060
2007
Tahinci, E., C. A. Thorne, J. L. Franklin, A. Salic, K. M. Christian, L. A. Lee, R. J. Coffey, and E. Lee, "Lrp6 is required for convergent extension during Xenopus gastrulation.", Development, vol. 134, issue 22, pp. 4095-106, 2007 Nov.
PMCID: PMC4428168 PMID: 17965054
2003
Thorne, C., and A. V. Lee, "Cross talk between estrogen receptor and IGF signaling in normal mammary gland development and breast cancer.", Breast Dis, vol. 17, pp. 105-14, 2003.
PMID: 15687681