林文傑 副研究員

Dr. Wen-Jye Lin   林文傑 副研究員                                                           Profile updated: Oct 21, 2021

Associate Investigator                                                                          

Immunology Research Center, National Health Research Institutes

[Contact Information]

Phone     +886-37-206166 Ext. 37605 / 37625

Fax           +886-37-586642

Email       wjlin@nhri.edu.tw

Address  35 Keyan Road, Zhunan, Miaoli County 350, Taiwan (R.O.C.)

   Research Interest and Specialty

I was blessed to have excellent scientists as my mentors, making for a rich learning environment. While in the US, I have chosen prostate cancer as a specialty of my research career and immunology as a sub-specialty. Over 4 years (2009-2013) as a junior faculty at the department of Pathology, University of Rochester Medical Center, NY, my latest work with the collaborators has uncovered several novel aspects of targeting androgen receptor (AR) in PCa cells/tumor-associated macrophages with androgen deprivation therapy (ADT) for the development of castration resistance and metastasis through induction of the chemokine CCL2, epithelial-mesenchymal transition, and STAT3 activation. Our findings suggest that the sole inhibition of AR as a therapeutic intervention against prostate cancer is intrinsically destined to fail, which has great impact on the design of traditional hormone therapy. This work was supported by the new investigator award, Congressionally-directed medical research program for PCa, Department of Defense, US in 2010.

After joining Immunology Research Center at NHRI in late 2013 as a principle investigator, the research focus of my laboratory surrounds the function of DUSPs (dual-specificity phosphatases) in both tumor immunology and various prominent cancers in Taiwan. I am investigating the role of DUSPs/immune signaling in the crosstalk between infiltrating immune cells and cancer cells, and determine how DUSP may affect immune cell function and control immune signaling for cancer development and progression. I believe targeting DUSPs and their downstream signaling mediators, such as inflammatory cytokines, could possibly represent a valuable therapeutic strategy against various cancers. Currently, my team has successfully adapted multiple approaches like bio-plex cytokine array, bio-informatics analysis, and RNA-seq to identify several potential targets that may promote tumor-mediated immunosuppression using DUSP genetically-modified mice that were bred with tumor mice. I truly welcome those of you who are interested in studying cancer immunology to join my team for pursing your graduate degree or postdoctoral training at Immunology Research Center, NHRI.

   Educations and Positions

  •  BS, Medical Technology, National Yang-Ming University. (1991)
  •  MS, Microbiology & Immunology, National Yang-Ming University. (1993)
  •  Medical lab technologist, STAT lab, Veterans General Hospital, Taipei. (1998)
  •  Ph.D, Pathology, University of Rochester School of Medicine & Dentistry. (2003)
  •  Postdoctoral Research Fellow, The Campbell Family Institute for Breast Cancer Research, University of Toronto,   Ontario, Canada. (2009)
  • Research Assistant Professor, Department of Pathology, University of  Rochester Medical Center, Rochester, NY. (2013)
  • Assistant investigator, Immunology Research Center, National Health  Research Institutes, Taiwan. (2021)
  • Associate investigator, Immunology Research Center, National Health  Research Institutes, Taiwan. (2021- )

   Honors

  • 1998-2003  Predoctoral Fellowship, NIH, US
  • 1999  Gordon Research Conference on Hormonal Carcinogenesis- Travel Award,   USA
  • 2004-2005  Prostate Cancer Training Grant Postdoctoral Fellowship at Princess Margaret Hospital, University of Toronto Health Network, Toronto, Ontario,  Canada
  • 2005-2006  Heart & Stroke/ Richard Lewar Center of Excellence Fellowship Award, Canada
  • 2006-2008  Postdoctoral Training Grant, Department of Defense Prostate Cancer Research  Program (PCRP) of the Office of the Congressionally-Directed Medical Research  (W81XWH-06-1-0051)
  • 2010-2013  New investigator Award, Department of Defense Prostate Cancer Program (PCRP) of the Office of the Congressionally-Directed Medical Research (W81XWH-10-1-0300) 

   Publications

  1. Lee, Y. F., W. J. Young,Lin W. J., C. R. Shyr, C. Chang (1999). “Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor.” J Biol Chem274(23): 16198-205. PMID10347174. No PMCID.
  2. Lee, Y. F., C. R. Shyr, T. H. Thin, Lin W. J., C. Chang (1999). “Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily.” Proc Natl Acad Sci USA96(26): 14724-9. 10611280. PMID10611280, PMC24715.
  3. Lin, H.K., S. Altuwaijri, Lin W. J., P.Y. Kan, L. Collins, C. Chang (2002). “Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with coregulators in prostate cancer cells.” J Biol Chem 277(39):36570-36576.PMID 12119296, No PMCID
  4. Lee, Y. F., Lin W. J*.et al (2002). “Activation of MAP kinase pathway by hydroxyflutamide: a possible mechanism for the hydroxyflutamide withdrawal syndrome”. Cancer Research62(21):6039-44. (*co-first authorship). PMID 12414626, No PMCID
  5. Lin, W. J., J. Li, Y.F. Lee, S. Altuwaijri, J.H. Ou, C. Chang (2003). “Suppression of Hepatitis B virus core promoter by the nuclear orphan receptor TR4.” J Biol Chem278(11):9353-60. PMID12522137, No PMCID
  6. Yang, Y., Wang, X., Dong, T., Kim, E., Lin, W. J., and Chang, C (2003). Identification of a novel testicular orphan receptor-4 (TR4)-associated protein as repressor for the selective suppression of TR4-mediated transactivation. J Biol Chem278: 7709-7717. PMID 12486131, No PMCID
  7. Altuwaijri S, Lin HK, Chuang KH, Lin W. J,Yeh S, Hanchett LA, Rahman MM, Kang HY, Tsai MY,Zhang Y, Yang L,Chang C (2003). Interruption of nuclear factor kappaB signaling by the androgen receptor facilitates 12-Otetradecanoylphorbolacetate-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells.Cancer Res Nov 1;63(21):7106-7112. PMID 14612503, No PMCID.
  8. Chuang, K. H., Y. F. Lee., Lin W.J., Yu-Jui Yvonne Wan, C Chang (2005). “Androgen receptor-retinoid X receptor interaction and mutual regulation”. Mol Endocrinol19(5):1200-1212. PMID 15650026, No PMCID
  9. Hsu CL, Chen YL, Ting HJ, Lin W. J, Yang Z, Zhang Y, Wang L, Wu CT, Chang HC, Yeh S, Pimplikar SW, Chang C (2005). Androgen Receptor (AR) NH2- and COOH-Terminal Interactions Result in the Differential Influences on the AR-Mediated Transactivation and Cell Growth. Mol Endocrinol19(2):350-61.PMID 15514032, No PMCID
  10. Chau H, Wong V, Chen NJ, Huang HL,Lin W.J,Mirtsos C, Elford AR, Bonnard M, Wakeham A,You-Ten AI, Lemmers B, Salmena L, Pellegrini M, Hakem R, Mak TW, Ohashi P, Yeh WC (2005) Cellular FLICE-inhibitory protein is required for T cell survival and cycling. J Exp Med 20 (3):405-13.PMID16043518, PMC2213079
  11. Lin W.J, Yeh WC (2005), Implication of Toll-like receptor and TNFa Signaling in Septic Shock. Shock24(3): 206-209. PMID 16135957, No PMCID
  12. Chen NJ, Mirtsos C, Suh D, Lu YC, Lin W.J,McKerlie C, Lee T, Baribault H, Tian H, Yeh WC.(2007). C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature446(7132): 203-207. PMID17322907, No PMCID
  13. 13.Liu N.C., Lin, W.J., Lee, Y.F., Collins L.L., Lin, H.Y., Hanson, R.W., Chang, C., (2007). Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis. Diabetes 56(12):2901-2909. PMID 17827404, No PMCID
  14. Chen NJ, Chio IC, Lin W. J, Duncan G, Chau H, Katz D, Huang HL, Pike KA, Hao Z, Su YW, Yamamoto K, de Pooter RF, Zúñiga-Pflücker JC, Wakeham A, Yeh WC, Mak TW (2008). Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors. Proc. Natl. Acad. Sci. USA105(34):12431-12434. PMID 18719121, PMC2518828.
  15. Lai JJ, Lai KP, Chuang KH, Chang P, Yu IC,Lin W. J, Chang C (2009). Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-alpha expression. J. Clin. Invest.Dec;119(12):3739-51. PMID: 19907077, PMCID: PMC2786793.
  16. Liu NC, Lin WJ, Yu IC, Lin HY, Liu S, Lee YF, Chang C., (2009). Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling. Endocrine.2009 Oct;36(2):211-7. PMID: 19618297.
  17. Su YW, Hao Z, Hirao A, Yamamoto K,Lin WJ, Young A, Duncan GS, Yoshida H, Wakeham A, Lang PA, Murakami K, Hermeking H, Vogelstein B, Ohashi P, Mak TW. (2011).14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1. Proc. Natl Acad Sci USA; 108(4):1555-1560. PMID: 21205887, PMCID: PMC3029705.
  18. Lee YF, Liu S, Liu NC, Wang RS, Chen LM, Lin WJ, Ting HJ, Ho HC, Li G, Puzas EJ, Wu Q, Chang C. Premature aging with impaired oxidative stress defense in mice lacking TR4. (2011). Am J Physiol Endocrinol Metab.301(1):E91-8. PMID: 21521714, PMCID: PMC3129845
  19. Collins LL, Lee YF, Ting HJ, Lin WJ, Liu NC, Meshul CK, Uno H, Bao BY, Chen YT, Chang C. (2011) The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice. Reprod Biol Endocrinol. 13;9:138. PMID:21995792, PMCID: PMC3212810
  20. Lin WJ, YW Su, YC Lu, Z Hao, I Chio,NJ Chen, A Brüstle, WY Li and Mak TW. (2011). Crucial Role for TRAF2 in Regulating NFκB2 Signaling that Contributes to Autoimmunity. Proc. Natl Acad Sci USA 2011 Nov 8;108(45):18354-9. PMID: 22042853, PMCID: PMC3215017.21.
  21. Wang X*, Lin WJ*, Lai KP, Izumi K, Xu D, Fang LY, Lu T, Lei Li1, Jiang Q, Xia J and Chang C (2012). Increased Infiltrated Macrophages in Benign Prostatic Hyperplasia: the Role of Stromal Androgen Receptor in Macrophage-induced Prostate Stromal Cell Proliferation. Journal of Biological Chemistry. 287(22):18376-85. PMID:22474290, PMCID:PMC3365773. *Co-first authorship
  22. Lu T*, Lin WJ*, Izumi K, Wang W, Xu D, Fang LY, Li L, Jian Q, JinJ, and Chang C (2012). Targeting Androgen Receptor to Suppress Macrophage-induced EMT and BPH Development. Molecular Endocrinology. 2012 Aug 21. PMID:22915828. *Co-first authorship
  23. Izumi K, Mizokami A, Lin WJ, Lai KP, and Chang C. Androgen Receptor Roles in the Development of Benign Prostate Hyperplasia (2013). American J. Pathology.Jun;182(6):1942-9. PMID:23570837
  24. Fang LY, Izumi K , Li L, Lai KP, Liang L, Miyamoto H, Lin WJ*, and Chang C*(2013). A Critical Role for AR/CCL4 axis in promotion of prostate tumorigenesis. Paper in press. Cancer Research. Sep 6. PMID:23878190. * co-corresponding author.
  25. Izumi K, Fang LY, Mizokami A, Namiki M, Li L,  Lin WJ*, and Chang C*(2013). Targeting Androgen Receptor-induced CCL2 Expression by STAT3 Activation Contributes to Prostate Cancer Metastasis. EMBO Mol Med. 2013 Sep;5(9):1383-401. PMID: 23982944. *co-corresponding author.
  26. Lin TH, Izumi K, Lee SO, Lin WJ, Yeh S, Chang C. Anti-androgen receptor ASC-J9 versus anti-    androgens MDV3100 (Enzalutamide) or Casodex (Bicalutamide) leads to opposite effects on prostate cancer metastasis via differential modulation of macrophage infiltration and STAT3-CCL2 signaling. Cell Death Dis. 2013 Aug 8;4:e764. PMID: 23928703.
  27. Chen M-Y, Chen Y-P, Wu M-S, Yu G-Y, Lin W-J, Tan T-H, et al. PP4 is essential for germinal center formation and class switch recombination in mice. PLoS One. 2014;9:e107505.
  28. Izumi K, Lin W-J, Miyamoto H, Huang C-K, Maolake A, Kitagawa Y, et al. Outcomes and predictive factors of prostate cancer patients with extremely high prostate-specific antigen level. J Cancer Res Clin Oncol. 2014;140:1413-9.
  29. Lin W-J*, Izumi K. Androgen receptor, ccl2, and epithelial-mesenchymal transition: A dangerous affair in the tumor microenvironment. Oncoimmunology. 2014;3:e27871. *corresponding authorship
  30. Izumi K*, Mizokami A, Lin HP, Ho HM, Iwamoto H, Maolake A, Natsagdorj A, Kitagawa Y, Kadono Y, Miyamoto H, Huang CK, Namiki M, Lin W-J*. Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer. Oncotarget, 2016 Feb 16;7(7):8389-98. *Co-corresponding authorship
  31. Maolake, A., Izumi, K., Shigehara, K., Natsagdorj, A., Iwamoto, H., Kadomoto, S., Takezawa, Y., Machioka, K., Narimoto, K., Namiki, M., Lin, W-J., Wufuer, G., & Mizokami, A. Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22–CCR4 axis. Oncotarget, 2017 Feb 7;8(6):9739-9751. doi: 10.18632/oncotarget.14185.
  32. Urata S, Izumi K, Hiratsuka K, Maolake A, Natsagdorj A, Shigehara K, Iwamoto H, Kadomoto S, Makino T, Naito R, Kadono Y, Lin W–J, Wufuer G, Narimoto K, Mizokami A. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment. Cancer Sci. 2018 Mar; 109(3):724-731. doi: 10.1111/cas.13494.
  33. Liao FH, Wu TH, Huang YT, Lin W–J, Su CJ, Jeng US, Kuo SC, Lin SY. Subnanometer Gold Clusters Adhere to Lipid A for Protection against Endotoxin-Induced Sepsis. Nano Lett. 2018 Apr 12. PMID: 29589756.
  34. Chen MY, Hsu WC, Hsu SC, Yang YS, Chuang TH, Lin W-J, Tan TH, Su YW. PP4 deficiency leads to DNA replication stress that impairs immunoglobulin class switch efficiency. Cell Death Differ. 2018 Sep 20. doi: 10.1038/s41418-018-0199-z.
  35. Lin HP ,Ho HM, Chang CW, Yeh SD, Su YW, Tan TH, Lin WJ*. (2019) DUSP22 suppresses prostate cancer proliferation by targeting the EGFR/AR axis. FASEB J. 2019 Dec, 33 (12), 14653-14667. *corresponding authorship
  36. Liao FH, Wu TH, Yao CN, Huang YT, Chen SP, Yeh LC, Shu-Yi Lin* and Lin WJ* (2021). A pH-responsive double-caged platinum nanoprodrug inhibits tumor-intrinsic HIF-1a/PD-L1 axis. ACS AppliedBio Materials. Paper in press. https://pubs.acs.org/doi/full/10.1021/acsabm.1c00667. *co-corresponding authorship

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