个人简介

EducationPhD Dept. Bioscience & Biotechnology, Sejong University, Korea (2000-2004)MS Dept. Applied Biology, Dongguk University, Korea (1998-2000)BS Dept. Biology, Dongguk University, Korea (1990-1998)Academic and Professional Experience2019-present Associate Professor, Faculty of Health Sciences, University of Macau2013-2019 Assistant Professor, Faculty of Health Sciences, University of Macau2011-2013 Research Associate, Dept. Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA2006-2011 Postdoctoral Fellow, Dept. Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA2005-2006 Research Scientist, Biotechnology Industrialization Institute, Yonsei University, Seoul, Korea2004-2005 Lecturer, Dept. Bioscience & Biotechnology, Sejong University, Seoul, Korea2000-2001 Research Assistant, Dept. Bioscience & Biotechnology, Sejong University, Seoul, KoreaCourse OutlinesHSCI4003 Pharmacology and Chemical Biology HSCI4009 Toxicology

研究领域

[Exploiting synthetic lethality for cancer precision medicine]Synthetic lethality is a genetic interaction where a single gene deficiency is tolerable for cell viability while the combination of deficiencies in two genes leads to cell death. The concept of the synthetic lethality has been widely exploited in cancer research field because a large portion of cancer has loss-of-function mutations in tumor suppressor genes. Synthetic lethality utilizes the mutations in tumor suppressor genes as a mark for selectivity of anticancer drugs. Pharmacological or genetic perturbation of a synthetic lethality partner of a tumor suppressor will cause selective lethality of the cancer cells that carry the tumor suppressor mutation. As it provides a strong cancer cell selectivity, synthetic lethality is one of core approaches for cancer precision medicine. My lab is studying major tumor suppressor genes, including p53, PTEN, RB1, BRCA1, ARID1A, and SMAD4, and is expanding to newly identified tumor suppressors. We have established isogenic cell pairs for the tumor suppressor genes and actively working on identifying synthetic lethality partners using chemical and genetic screenings.

PatentsInternational patent: WO/2010/042163 – Quinoline compounds as inhibitors of angiogenesis, human methionine aminopeptidase, and SIRT1, and methods of treating disorders. Liu JO, Shim JS, Chong CR, and Bhat S. 04/15/2010Korea patent: 1006410760000 – A novel aminopeptidase N Inhibitor. Kwon HJ, Lee J and Shim JS. 10/25/2006Korea patent: 1006046970000 – A novel calmodulin antagonist and an immunosuppressive agent comprising thereof. Kwon HJ, Shim JS and Lee J. 07/19/2006International patent: WO/2003/105751 – Novel curcumin derivatives. Kwon HJ, Shim JS, Kim JH, Choi SH, Shin JH and Rho JR. 12/24/2003

近期论文

Representative PublicationsZhang, B. Y., Lyu, J. F., Yang, E. J., Liu, Y. F., Wu, C. J., Pardeshi, L., Tan, K. L., Chen, Q., Xu, X. L., Deng, C. X., and Shim, J. S. (2020) Class I Histone Deacetylase Inhibition Is Synthetic Lethal with BRCA1 Deficiency in Breast Cancer Cells. Acta Pharm Sin B 10, 615-627Liu, Y. F., Yang, E. J., Shi, C. X., Mou, P. K., Zhang, B. Y., Wu, C. J., Lyu, J. F., and Shim, J. S. (2020) Histone Acetyltransferase (HAT) P300/CBP Inhibitors Induce Synthetic Lethality in PTEN-Deficient Colorectal Cancer Cells through Destabilizing AKT. Int J Biol Sci 16, 1774-1784Lyu, J. F., Yang, E. J., and Shim, J. S. (2019) Cholesterol Trafficking: An Emerging Therapeutic Target for Angiogenesis and Cancer. Cells 8, E389Zhang, B. Y., Lyu, J. F., Liu, Y. F., Wu, C. J., Yang, E. J., Pardeshi, L., Tan, K., Wong, K. H., Chen, Q., Xu, X. l., Deng, C. X., and Shim, J. S. (2018) BRCA1 Deficiency Sensitizes Breast Cancer Cells to Bromodomain and Extra-Terminal Domain (BET) Inhibition. Oncogene 37, 6341-6356Wu, C. J., Lyu, J. F., Yang, E. J., Liu, Y. F., Zhang, B. Y., and Shim, J. S. (2018) Targeting AURKA-CDC25C Axis to Induce Synthetic Lethality in ARID1A-Deficient Colorectal Cancer Cells. Nat Commun 9, 3212Lyu, J. F., Yang, E. J., Head, S., Ai, N., Zhang, B. Y., Wu, C. J., Li, R. J., Liu, Y. F., Chakravarty, H., Zhang, S. L., Tam, K. Y., Dang, Y. J., Kwon, H. J., Ge, W., Liu, J. O., and Shim, J. S. (2018) Astemizole Inhibits mTOR Signaling and Angiogenesis by Blocking Cholesterol Trafficking. Int J Biol Sci 14, 1175-1185Liu, Y., Yang, E. J., Zhang, B. Y., Miao, Z. Q., Wu, C. J., Lyu, J. F., Tan, K., Poon, T. C. W., and Shim, J. S. (2018) PTEN Deficiency Confers Colorectal Cancer Cell Resistance to Dual Inhibitors of FLT3 and Aurora kinase A. Cancer Lett 436, 28-37Lyu, J. F., Yang, E. J., Head, S., Ai, N., Zhang, B. Y., Wu, C. J., Li, R. J., Liu, Y. F., Yang, C., Dang, Y. J., Kwon, H. J., Ge, W., Liu, J. O., and Shim, J. S. (2017) Pharmacological Blockade of Cholesterol Trafficking by Cepharanthine in Endothelial Cells Suppresses Angiogenesis and Tumor Growth. Cancer Lett 409, 91-103Head, S., Shi, W., Yang, E. J., Nacev, B., Hong, S., Pasunooti, K., Li, R. J., Shim, J. S., and Liu, J. O. (2017) Simultaneous Targeting of Npc1 and Vdac1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis. Acs Chem Biol 12, 174-182Shim, J. S., Li, R. J., Bumpus, N., Head, S., Pasunooti, K. K., Yang, E. J., Lv, J. f., Shi, W., and Liu, J. O. (2016) Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole. Clin Cancer Res 22, 2709-2720Du, B. W., and Shim, J. S. (2016) Targeting Epithelial–Mesenchymal Transition (Emt) to Overcome Drug Resistance in Cancer. Molecules 21, 965Cho, Y. S., Yen, C. n., Shim, J. S., Kang, D. H., Kang, S. W., Liu, J. O., and Kwon, H. J. (2016) Antidepressant Indatraline Induces Autophagy and Inhibits Restenosis Via Suppression of mTOR/S6 Kinase Signaling Pathway. Sci Rep-Uk 6, 34655Wang, G. L., Rajpurohit, S., Delaspre, F., Walker, S., White, D., Ceasrine, A., Kuruvilla, R., Li, R. j., Shim, J. S., Liu, J. O., Parsons, M., and Mumm, J. (2015) First Quantitative High-Throughput Screen in Zebrafish Identifies Novel Pathways for Increasing Pancreatic Β-Cell Mass. Elife 4, e08261Shim, J. S., Li, R. J., Lv, J. F., Head, S., Yang, E. J., and Liu, J. O. (2015) Inhibition of Angiogenesis by Selective Estrogen Receptor Modulators through Blockade of Cholesterol Trafficking Rather Than Estrogen Receptor Antagonism. Cancer Lett 362, 106-115Head, S. A., Shi, W., Zhao, L., Gorshkov, K., Pasunooti, K., Chen, Y., Deng, Z., Li, R. j., Shim, J. S., Tan, W., Hartung, T., Zhang, J., Zhao, Y., Colombini, M., and Liu, J. O. (2015) Antifungal Drug Itraconazole Targets Vdac1 to Modulate the Ampk/mTOR Signaling Axis in Endothelial Cells. Proceedings of the National Academy of Sciences 112, E7276-E7285Wang, M. H., Shim, J. S., Li, R. J., Dang, Y. J., He, Q. L., Das, M., and Liu, J. O. (2014) Identification of an Old Antibiotic Clofoctol as a Novel Activator of Unfolded Protein Response Pathways and an Inhibitor of Prostate Cancer. Brit J Pharmacol 171, 4478-4489Shim, J. S., and Liu, J. O. (2014) Recent Advances in Drug Repositioning for the Discovery of New Anticancer Drugs. Int J Biol Sci 10, 654-663Kamiyama, H., Rauenzahn, S., Shim, J. S., Karikari, C. A., Feldmann, G., Hua, L., Kamiyama, M., Schuler, F. W., Lin, M. T., Beaty, R. M., Karanam, B., Liang, H., Mullendore, M. E., Mo, G., Hidalgo, M., Jaffee, E., Hruban, R. H., Jinnah, H. A., Roden, R. B., Jimeno, A., Liu, J. O., Maitra, A., and Eshleman, J. R. (2013) Personalized Chemotherapy Profiling Using Cancer Cell Lines from Selectable Mice. Clin Cancer Res 19, 1139-1146Choi, S. M., Kim, Y., Shim, J. S., Park, J. T., Wang, R. H., Leach, S. D., Liu, J. O., Deng, C., Ye, Z., and Jang, Y. Y. (2013) Efficient Drug Screening and Gene Correction for Treating Liver Disease Using Patient-Specific Stem Cells. Hepatology 57, 2458-2468Shim, J. S., Rao, R., Beebe, K., Neckers, L., Han, I., Nahta, R., and Liu, J. O. (2012) Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV Protease Inhibitor Nelfinavir. J Natl Cancer Inst 104, 1576-1590Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S. J., Anders, R. A., Liu, J. O., and Pan, D. (2012) Genetic and Pharmacological Disruption of the TEAD-YAP Complex Suppresses the Oncogenic Activity of YAP. Genes Dev 26, 1300-1305Rovira, M., Huang, W., Yusuff, S., Shim, J. S., Ferrante, A. A., Liu, J. O., and Parsons, M. J. (2011) Chemical Screen Identifies FDA-Approved Drugs and Target Pathways That Induce Precocious Pancreatic Endocrine Differentiation. Proc Natl Acad Sci U S A 108, 19264-19269Platz, E. A., Yegnasubramanian, S., Liu, J. O., Chong, C. R., Shim, J. S., Kenfield, S. A., Stampfer, M. J., Willett, W. C., Giovannucci, E., and Nelson, W. G. (2011) A Novel Two-Stage, Transdisciplinary Study Identifies Digoxin as a Possible Drug for Prostate Cancer Treatment. Cancer Discov 1, 68-77Shim, J. S., Matsui, Y., Bhat, S., Nacev, B. A., Xu, J., Bhang, H. E., Dhara, S., Han, K. C., Chong, C. R., Pomper, M. G., So, A., and Liu, J. O. (2010) Effect of Nitroxoline on Angiogenesis and Growth of Human Bladder Cancer. J Natl Cancer Inst 102, 1855-1873Shim, J. S., Lee, H. K., Park, H. M., Kim, J. O., Kim, E. K., Hwang, K. H., Kim, K. T., Park, S. W., Lee, J. H., and Kwon, H. J. (2005) Development of Anangiogenesis-Focused cDNA Chip and Validation of Its Functionality. Exp Mol Med 37, 365-370Shim, J. S., Lee, J., Park, H. J., Park, S. J., and Kwon, H. J. (2004) A New Curcumin Derivative, HBC, Interferes with the Cell Cycle Progression of Colon Cancer Cells Via Antagonization of the Ca2+/Calmodulin Function. Chem Biol 11, 1455-1463Shim, J. S., Lee, H. S., Shin, J., and Kwon, H. J. (2004) Psammaplin A, a Marine Natural Product, Inhibits Aminopeptidase N and Suppresses Angiogenesis in Vitro. Cancer Lett 203, 163-169Shim, J. S., and Kwon, H. J. (2004) Chemical Genetics for Therapeutic Target Mining. Expert Opin Ther Targets 8, 653-661Shim, J. S., Kim, D. H., and Kwon, H. J. (2004) Plakoglobin Is a New Target Gene of Histone Deacetylase in Human Fibrosarcoma HT1080 Cells. Oncogene 23, 1704-1711Shim, J. S., Kim, J. H., Cho, H. Y., Yum, Y. N., Kim, S. H., Park, H. J., Shim, B. S., Choi, S. H., and Kwon, H. J. (2003) Irreversible Inhibition of CD13/aminopeptidase N by the Antiangiogenic Agent Curcumin. Chem Biol 10, 695-704