Recent, Selected Original Research

1. Koikawa, K., Kibe, S., Suizu, F., Sekino, N. Kim, N., Manz, T. D. Pinch, B. J., Akshinthala, D., Verma, A., Gaglia, G., Nezu, Y., Ke, Z., Qiu, C., Ohuchida, K., Oda, Y., Lee, T. H., Wegiel, B., Clohessy, J. G., Sanatagata, S., Wulf, G. M., Hidalgo, M., Muthuswamy, S., Nakamura, M., Gray, N., Zhou, X. Z.* and Lu, K. P.* 2021. Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. Cell, 184: 4753-4771 (* equal contribution and corresponding authorship).

2. Qiu, C., Albayram, O., Kondo, A., Wang, B., Kim, N., Arai, K., Tsai, C.Y., Bassal, M. A., Herbert, M. K., Washida, K., Angeli, P., Kozono, S., Stucky, J. E., Baxley, S., Lin, Y. M., Sun, Y., Rotenberg, A., Caldarone, B. J., Bigio, E. H., Chen, X., Tenen, D. G., Zeidel, M., Lo, E. H., Zhou, X. Z.* and Lu, K. P.*  2021, Cis P-tau underlies vascular contribution to cognitive impairment and dementia, and is effectively targeted by immunotherapy in mice. Science Transl Med 13: eaaz7615.

3. Kim, N., Wang, B., Koikawa, K., Nezu, Y., Qiu, C., Lee, T. H.*, and Zhou X. Z.* 2021. Inhibition of death-associated protein kinase 1 attenuates cis P-tau and neurodegeneration in traumatic brain injury. Prog Neurobiol 203: 102072.

4. Kozono, S., Lin, Y. M., Seo, H. S., Pinch, B., Lian, X., Qiu, C., Herbert, M. K., Chen, C. H., Tan,  L., Gao, Z. J., Massefski, W., Doctor, Z. M., Jackson, B. P., Chen, Y. Dhe-Paganon, S., Lu, K. P.* and Zhou, X. Z.*, 2018. Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nature Commun 9: 3069. (featured in a Editors’ Highlights page).

5. Nechama, M., Kwon, J., Wei, S., Tun-Kyi, A., Welner, R. S., Arredouani, M. S., Asara, J. M., Chen, C. H., Kobayashi, K. S., Israel, E., Zhou, X. Z., Nicholson, L. K.* and Lu, K. P.* 2018, The novel IL-33-Pin1-IRAK-M axis critical for type 2 immunity in IL-3-induced allergic airway inflammation. Nature Commun 9: 1603. 

6. Albayram, O., Kondo, A., Mannix, R., Smith, C., Li, C., Tsai, C. Y., Herbert, M. K., Qiu, J., Monuteaux, M., Driver, J. A., Yan, S., Gormley, W., Puccio, A. W., Okonkwo, D. O., Lucke-Wold, B., Bailes, J., Meehan, W., Zeidel, M., Lu, K. P.* and Zhou, X. Z.*, 2017. Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae. Nature Commun 8: 1000. 

7. Wei, S, Yoshida, N., Finn, G., Kozono, S., Nechama, M., Kyttaris, V. C., Zhou, X. Z., Tsokos, G. C. and Lu, K. P. 2016, Pin1-targeted therapy for systemic lupus erythematosus. Arthritis Rheumatol. 68: 2503-2513. 

8. Kondo, A., Shahpasand, K., Mannix, R., Qiu, J., Moncaster, J., Chen, C. H., Yao, Y., Lin, Y. M., Driver, J. A., Sun, Y., Wei, S., Luo, M. L., Albayram, O., Huang, P., Rotenberg, A., Ryo, A., Goldstein, L. E., Pascual-Leone, A., Mckee, A., Meehan, M., Zhou, X. Z.*and Lu, K. P.* 2015, Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy. Nature 523: 431-436 (Research Article) (Highlighted by the July 15 2015 issue of Nature Podcast). (Research highlight in Nat Rev Drug Discov. 2015; 14:599). 

9. Wei, S., Kozono, S., Kats, L., Li, W., Nechama, M., Li, W., Guarnerio, J., Bozkurt, G., Luo, M., You, M. H., Yao, Y. Kondo, A., Hu, H., Moerke, N. J., Cao, S., Reschke, M., Rego, E. M., LoCoco, F., Cantley, L., Lee, T. H., Wu, H., Zhang, Y., Pandolfi, P. P., Zhou, X. Z.* and Lu, K. P.* 2015, Active Pin1 as a target of ATRA in acute promyelocytic leukemia and breast cancer. Nature Med 21: 457-466.

10. Luo, M. L., Gong, C., Chen, C. H., Hu, H., Huang, P., Zheng, M., Yao, Y., Wei, S., Wulf, G., Lieberman, J., Zhou, X. Z., Song, E. and Lu, K. P. 2015, The Rab2A GTPase is a novel breast cancer stem-promoting gene that enhances tumorigenesis via activating Erk signaling. Cell Rep 11:111-24.

11. Chen, C. H., Li, W., Sultana, R., You, M. Y., Kondo, A., Shahpasand, K., Kim, B. O., Luo, M., Nechama, M., Lin, Y. M., Yao, Y., Lee, T. H., Zhou, X. Z., Swomley, A. M., Butterfield, D. A., Zhang, Y. and Lu, K. P. 2015, Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer’s disease. Neurobiol Dis 76: 13-23 (the Cover Story).

12. Luo, M. L., Gong, C., Chen, C. H., Hu, H., Huang, P., Zheng, M., Yao, Y., Wei, S., Guo, W., Reinhard, F., Wulf, G., Lieberman, J., Zhou, X. Z., Song, E. and Lu, K. P. 2014, Prolyl isomerase Pin1 acts downstream of miR-200 to promote cancer stem-like cell traits in breast cancer. Cancer Res 74: 3603-3616.

13. Chen, C. H., Chang, C. C., Lee, T. H., Luo, M., Huang, P. Liao, P. H., Wei, S., Li, F. A., Chen, R. H., Zhou, X. Z., Shih, H. M, and Lu, K. P. 2013. SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function. Cancer Res 73: 3951-3962.

14. Min, S. H., Lau, A. W., Lee, T. H., Inuzuka, H., Wei, S. Huang, P., Shaik, S. Lee, D. Y. Finn, G., Balastik, M., Chen, C. H., Luo, M., Tron, A. E., DeCaprio, J. A., Zhou, X. Z., Wei, W. and Lu, K. P. 2012. Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol. Cell 46: 771-783.

15. Nakamura, K., Greenwood, A., Binder, L., Bigio, E. H., Denial, S. J., Nicholson, L., Zhou, X. Z.* and Lu, K. P.* 2012. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease. Cell 149: 232-244.

16. Driver, J. A., Beiser, A., Au, R., Kreger, B., Splansky, G. L., Kurth, T., Kiel, D., Lu, K. P., Seshadri, S. & Wolf, P. A. 2012. Inverse association between cancer and Alzheimer’s disease: Results from the Framingham study. BMJ 344: e1442. (Comments in BMJ 344: e1662).

17. Nakamura, K., Kosugi, I, Lee, D. Y., Hafner, A., Sinclair, D. A., Ryo, A., and Lu, K. P. 2012. Prolyl isomerase Pin1 regulates neuronal differentiation via β-catenin. Mol Cell Biol 32: 2966-2978.

18. Tun-Kyi, A., Finn, G., Greenwood, A., Nowak, M., Lee, T. H., Asara, J. M., Tsokos, G. C., Fitzgerald, K., Israel, E., Li, X., Exley, M., Nicholson, L. K. and Lu, K. P. 2011, Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nature Immunol 12: 733-741.

19. Lee, T. H., Chen, C. H., Suizu, F., Huang, P., Schiene-Fischer, C., Daum, S., Zhang, J. Y., Goate, A., Hwa Chen, R. H., Zhou, X. Z., and Lu, K. P. 2011. Death-associated protein kinase 1 phosphoylates Pin1 and Inhibits its prolyl isomerase activity and cellular function. Mol Cell42:147-159 (Preview in Mol. Cell 42:139-41) (Highlighted by the April 2011 issue of Cell Podcast).

20. Zhou, X. Z.*, Huang P., Lee, T. H., Shi, R., Lu, G. Bronson, R. and Lu, K. P.* 2011, The telomerase inhibitor PinX1 is a major haploinsufficent tumor suppressor essential for chromosome stability in mice. J Clin Invest 121: 1266-1282 (Commentary in J. Clin. Invest. 121, 1242-1244) (The Cover Story).

21. Lee, T. H., Lim, J., Tun-Kyi, A., Finn, G., Shi, R., Balastik, M., Pastorino, L., Wulf, Zhou, X. Z.* and Lu, K. P.* 2009, Essential role of Pin1 in the regulation of TRF1 stability and telomere maintenance. Nature Cell Biol 11: 97-105.

22. Lim, J., Balastik, M., Lee, T. H. Liou, Y. C., Sun, A., Finn, G., Pastorino, L. Lee, V. M.-Y. and Lu, K. P. 2008, Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy. J Clin Invest 118: 1877-1889 (Highlighted “In this Issue” J. Clin. Invest. 118: 1585).

23. Pastorino, L., Sun, A., Lu, P. J., Zhou, X. Z., Balastik, M., Finn, G., Wulf, G., Lim, J., Li, S. H., Li, X., Xia, W., Nicholson, L. and Lu, K. P. 2006, The prolyl isomerase Pin1 regulates amyloid precursor protein processing and Amyloid-beta production. Nature440: 528-534 (News and Views in Nature Med. 12: 392-393).

24. Suizu, F., Ryo, A., Wulf, G., and Lu, K. P.2006, Pin1 regulates centrosome duplication and its overexpression induces centrosome amplification, chromosome instability and oncogenesis. Mol Cell Biol 26: 1463-1479. (The Cover Story). 

25. Lee, T. H., Perrem, K., Harper, W., Lu, K. P.*and Zhou, X. Z.* 2006, The F-box protein Fbx4 targets Pin2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance. J Biol Chem 281:759-768.

26. Wulf, G., Garg, P., Liou, Y. Y., Iglehart, D. and Lu, K. P. 2004, Modeling breast cancer in vivo and ex vivo uncovers an essential role for Pin1 in tumorigenesis. EMBO J 23: 3397-3407. 

27. Bao, L., Kimzey, A., Sauter, G., Sowadski, J., Lu, K. P.* and Wang, D.* 2004, Prevalent Overexpression of Prolyl Isomerase Pin1 in Human Cancers. Am J Pathol.164: 1727-1737.

28. Ayala, G., Wang, D., Wulf, G., Kimzey, A., Frolov, A., Le, R., Sowadski, J., Wheeler, T., Lu, K. P.* and Bao, L.* 2003, Pin1 is a novel prognostic marker in prostate cancer. Cancer Res. 63: 6244-6251.

29. Ryo, A., Suizu, F., Yoshida, Y., Perrem , K., Liou, Y. C., Wulf, G., Rottapel, R., Yamaoka, S., and Lu, K. P. 2003, Regulation of NF-kappaB signaling by Pin1-catalyzed prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell 12: 1413-1426 (Preview in Mol. Cell 12: 1344-1345).

30. Zheng, H., You, H., Zhou, X. Z., Murray, S. A., Uchida, T., Wulf, G., Gu, L., Tang, X., Lu, K. P. and Xiao, Z. X. 2002, The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature419: 849-853 (News and Views in Nature 419: 829-831). Erratum in: Nature 420: 445. 

31. Wulf, G. M., Liou, Y. C., Ryo, A., Lee, S. W., and Lu, K. P. 2002, Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage. J Biol Chem 277: 47976-47979 (Accelerated Publication).

32. Liou, Y.-C., Sun, A., Ryo, A., Zhou, X. Z., Yu, Z.-X., Huang, H.-K., Bronson, R., Uchida, T., Bing, G., Li, X., Hunter, T. and Lu, K. P. 2003, Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424: 556-561.

33. Liou, Y.-C., Ryo, A., Huang, H.-K., Lu, P. J., Fujimori, F., Uchida, T. Bronson, R. Hunter, T. and Lu, K. P. 2002, Loss of Pin1 function in the mouse resembles the cyclin D1-null phenotypes. Proc Natl Acad Sci USA 99: 1335-1340 (Track II direct submission).

34. Zhou, X. Z. and Lu, K. P. 2001, The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell107: 347-359.

35. Ryo. A., Wulf, G. M., Nakamura, M. Liou, Y. Lu, K. P. 2001, Pin1 regulates turnover and subcellular localization of beta-catenin by modulating its interaction with the tumor suppressor APC. Nature Cell Biol 3: 793-801.

36. Wulf, G. M., Ryo, A., Wulf, G. G., Lee, S. W., Niu, T. and Lu, K. P. 2001, Pin1 is overexpressed in breast cancer and potentiates the transcriptional activity of phosphorylated c-Jun towards the cyclin D1 gene. EMBO J 20: 3459-3472. 

37. Zhou, X. Z., Kops, O., Werner, A., Shen, M. Lu, P. J., Küllertz, G., Fischer, G., and Lu, K. P. 2000. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and Tau protein. Mol Cell 6: 873-883.

38. Lu, P.-J., Wulf, G., Zhou, X. Z., Davies, P. and Lu, K. P. 1999, Prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399: 784-788 (News and Views in Nature, 399: 739-740).

39. Lu, P.-J., Zhou, X. Z., Shen, M. and Lu, K. P. 1999, Function of WW domains as phosphoserine or phosphothreonine-binding modules. Science283:1325-1328 (News Focus in Science 283: 1248-1249).

40. Shen, M., Stukenberg, P. T., Kirschner, M. W. and Lu, K. P. 1998, The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Genes Dev. 12: 706-720.

41. Ranganathan, R., Lu, K. P., Hunter, T. and Noel, J. 1997, Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent. Cell 89: 875-886.

42. Yaffe, M., Schutkowski, M., Shen, M., Zhou, X. Z., Stukenberg, P. T., Rahfeld, J.-U., Xu, J., Kuang, J., Kirschner, M. W., Fischer, G., Cantley, L. and Lu, K. P. 1997, Sequence-specific and phosphorylation-dependent proline isomerization: A potential mitotic regulatory mechanism. Science278:1957-1960 (Research News in Science 278:1883-1884).

43. Lu, K. P., Hanes, S. D. and Hunter, T. 1996, A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380: 544-547.

44. Lu, K. P. and Hunter, T. 1995, Evidence for a NIMA-like mitotic pathway in vertebrate cells. Cell 81: 413-424.

45. Lu, K. P. and Means, A. R. 1994, Expression of the noncatalytic domain of the NIMA protein kinase causes a G2 arrest in Aspergillus nidulans. EMBO J132: 103-2113.