Liu, Jun - Johns Hopkins University - Department of Medicine

个人简介

Dr. Jun Liu is a professor of pharmacology and molecular sciences and oncology at the Johns Hopkins University School of Medicine. His research focuses on the interaction between chemistry, biology and medicine. Dr. Liu serves as the co-leader for the Cancer Chemical and Structural Biology Program for the Johns Hopkins Kimmel Cancer Center. Dr. Liu is the director of the Johns Hopkins Drug Library, where he and his collaborators aim to find new uses for often-forgotten drugs. Among the drug library's notable discoveries is that itraconazole, a widely used antifungal antibiotic, is a potent inhibitor of new blood vessel formation. To date, itraconazole has shown efficacy in treating non-small cell lung cancer in combination with pemetrexed, metastatic and castration-resistant prostate cancer and basal cell carcinoma. Dr. Liu received his undergraduate degree in chemistry from Nanjing University in Nanjing, China. He earned his M.S. in organic chemistry from The Ohio State University and his Ph.D. in biochemistry from the Massachusetts Institute of Technology. He was a postdoctoral fellow in the Department of Chemistry at Harvard University and a research associate at the National Institutes of Health. Prior to joining Johns Hopkins, Dr. Liu was an associate professor in the Center for Cancer Research and the departments of biology and chemistry at the Massachusetts Institute of Technology. Dr. Liu's work was recognized with a Director's Pioneer Award from the National Institutes of Health in 2010.

研究领域

Dr. Liu's primary research interest lies at the interface between chemistry, biology and medicine. He and his research team employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases, from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases. Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation. Current projects include the exploration of the existing drug space for novel pharmacological activities with translational potential; learning from nature—using natural products as probes of eukaryotic transcription and translation processes; and imitating nature—generating natural product-inspired macrocyclic combinatorial libraries for the discovery of novel inhibitors of protein-protein interactions.

近期论文

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Chong, C.R., Chen, X., Shi, L., Liu, J.O., and Sullivan, D.J. A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol, 2, 415-416, 2006. Pub Med Reference Chong, C.R., Xu, J., Lu, J., Bhat, S., Sullivan, D.J., Jr., Liu, J.O. Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem Biol, 2, 263-70, 2007. Pub Med Reference Kim, J., Tang, J.Y., Gong, R., Kim, J., Lee, J.J., Clemons, K.V., Chong, C.R., Chang, K.S., Fereshteh, M., Gardner, D., Reya, T., Liu, J.O., Epstein, E. H., Stevens, D. A., Beachy, P. A. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 17, 388-399, 2010. Pub Med Reference Xu, J., Dang, Y., Ren, Y.R., Liu, J.O. Cholesterol trafficking is required for mTOR activation in endothelial cells. Proc Natl Acad Sci USA, 107, 4764-9, 2010. Pub Med Reference Shim, 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., Liu, J.O. Effect of nitroxolibne on angiogenesis and growth of human bladder cancer. J Natl Cancer Inst, 102, 1855-1873, 2010. Pub Med Reference Head, 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., Liu, J.O. Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells. Proc Natl Acad Sci USA, 112, E7276-7285, 2015. Pub Med Reference Shim, J.S., Li, R.J., Bumpus, N.N., Head, S.A., Kumar Pasunooti, K., Yang, E.J., Lv, J., Shi, W., and Liu, J.O. Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole. Clin Cancer Res, 22, 2709-2720, 2016. Pub Med Reference Head, S.A., Shi, W. Q, Yang, E.J., Nacev, B.A., Hong, S.Y., Pasunooti, K.K., Li, R.J., Shim, J.S., and Liu, J.O. Simultaneous Targeting of NPC1 and VDAC1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis. ACS Chem Biol, 12, 174-182, 2017. Pub Med Reference Low, W.-K., Dang, Y., Schneider-Poetsch, T., Shi, Z., Choi, N.S., Merrick, W.C., Romo, D., Liu, J.O. Inhibition of eukaryotic translation initiation by the marine natural product pateamine A. Mol Cell, 20, 709-722, 2005. Pub Med Reference Schneider-Poetsch, T., Ju, J., Eyler, D.E., Dang, Y., Bhat, S., Merrick, W.C., Green, R., Liu, J.O. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol, 6, 209-217, 2010. Pub Med Reference Titov, D.V., Gilman, B., He, Q.L., Bhat, S., Low, W.K., Dang, Y., Smeaton, M., Demain, A.L., Miller, P.S., Kugel, J.F., Goodrich, J.A., Liu, J.O. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat Chem Biol, 7, 182-188. 2011. Pub Med Reference McClary, B., Zinshteyn, B., Meyer, M., Jouanneau, M., Pellegrino, S., Yusupova, G., Schuller, A., Reyes, J.C.P., Lu, J., Guo, Z., Ayinde, S., Luo, C., Dang, Y., Romo, D., Yusupov, M., Green, R., Liu, J.O. Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A. Cell Chem Biol, 24, 605-613, 2017. Pub Med Reference He, Q.L., Titov, D.V., Li, J., Tan, M., Ye, Z., Zhao, Y., Romo, D., Liu, J.O. Covalent modification of a cysteine residue in the XPB subunit of the general transcription factor TFIIH through single epoxide cleavage of the transcription inhibitor triptolide. Angew Chem Int Ed, 54, 1859-1863, 2014. Pub Med Reference He, Q.L., Minn, I., Wang, Q., Xu, P., Head, S.A., Datan, E., Yu, B., Pomper, M.G., Liu, J.O. Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation. Angew Chem Int Ed, 55, 12035-12039, 2016. Pub Med Reference Youn, H.-D., Sun, L., Prywes, R., Liu, J.O. Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2. Science, 286, 790-793, 1999. Pub Med Reference Han, A., Pan, F., Stroud, J.C., Youn, H.–D., Liu, J.O., Chen, L. Structural basis of sequence-specific recruitment of transcription corepressor Cabin1 by Myocyte Enhancer Factor-2. Nature, 422, 730-734, 2003. Pub Med Reference Pan, F., Sun, L., Dardian, D.B., Whartenby, K.A., Pardoll, D.M., Liu, J.O. Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin. Nature, 445, 433-436, 2007. Pub Med Reference Li, R.J., Xu, J., Fu, C., Zhang, J., Zheng, Y.G., Jia, H., Liu, J.O. Regulation of mTORC1 by lysosomal calcium and calmodulin. Elife, 5, e19360, 2016. Pub Med Reference Li, W., Bhat, S., Liu, J.O. (2011) A simple and efficient route to the FKBP-binding domain from rapamycin. Tetrehedron Lett, 52, 5070-5072, 2011. Pub Med Reference Guo, Z., Hong, S.Y., Wang, J., Liu, W., Peng, H., Das, M., Li, W., Rehan,S., Bhat, S., Peiffer, B., Tse, C.-M., Tarmakova, Z., Schiene-Fischer, C., Fischer, G., Coe, I., Paavilainen, V.O., Sun, Z., Liu, J.O. Rapafucins, rapamycin-inspired macrocycles with new target specificity. Nat Chem, 11, 254-263, 2019. Pub Med Reference