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    (Hsi-Hsien Lin)


研究室分子免疫(Molecular Immunology)


學校/國家University of Tennessee/U.S.A.




研究室現有: 博士後研究員 1

博士班研究生 1

碩士班研究生 2

專任研究助理 4

大學部專題生 3




  The research of my laboratory focuses principally on the functions and regulation of adhesion GPCRs. Specific interest includes:

1. The identification and characterization of, and the structural-functional study of the EGF-TM7 receptors, including EMR2, CD97 and F4/80.

2. The signaling pathways of EMR2 and CD97 receptors.

3. The role of adhesion-GPCRs in osteoclast differentiation and function.

4. Molecular and functional characterization of BFPP-associated GPR56 mutations.

5. The identification of the cellular ligand(s) of GPR56.

6. The role of GPR56 in tumor biology.

7. The expression and functional characterization of GPR56 in immune system.


We are well experienced in various biological assays of macrophage and neutrophil functions as well as tumor biology. Most modern technologies in molecular biology, cell biology, immunology, proteomics and biochemistry are well established in the laboratory.



1. 類上皮生長因子七次穿膜受體其特性的研究以及有關於他們特殊結構的探討,當中包含下列幾個分子:EMR2CD97F4/80

2. EMR2CD97受體的訊息傳導的研究

3. 研究黏合型G蛋白質耦合受體在蝕骨細胞分化與功能所扮演的角色

4. 探討人類腦部前額疾病BFPP的致病基因GPR56的功能與結構的特性

5. 尋找GPR56在細胞上的受質

6. GPR56在腫瘤生物學中所扮演的角色

7. 探討GPR56在免疫細胞表現與功能所扮演的角色




 *: corresponding author; &: co-first author


1. C.-C. Hsiao, H.-Y. Chen, G.-W. Chang and H.-H. Lin* 2011 GPS autoproteolysis is required for CD97 to up-regulate the expression of N-cadherin that promotes homotypic cell-cell aggregation. FEBS Letters 585(2):313-318. (SCI, IF=3.623) (corresponding author)

2. J. Q. Davies&, H.-H. Lin&*, M. Stacey&, S. Yona, G.-W. Chang, S. Gordon, J. Hamann, L. Campo, C. Han, A. L. Harris and S. B. Fox 2011 The leukocyte adhesion GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival. Oncology Reports 25(3):619-27. (SCI, IF=2.662) (co-first author, corresponding author)

3. N.-Y. Chiang, C.-C. Hsiao, Y.-S. Huang, H.-Y. Chen, I-J. Hsieh, G.-W. Chang, H.-H. Lin* 2011 Disease-associated GPR56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. J. Biol. Chem. 286(16): 14215-14225. (SCI, IF=4.125) (corresponding author) [Article featured on Global Medical Discovery (]

4. S. Gordon*, J. Hamann, H.-H. Lin, M. Stacey 2011 Celebrating 30 years: F4/80 and the related adhesion-GPCRs. Eur. J. Immunol. 41: 2472-2476 (SCI, IF=4.227) (invited review) (cover page)

5. Y.-M. Peng, Martijn D.B. van de Garde, K.-F. Cheng, P.A. Baars, R.A.W. van Lier, C.R. Mackay, H.-H. Lin*, and J. Hamann* 2011 Specific expression of GPR56 by human cytotoxic lymphocytes. J. Leukoc. Biol. 90: 735-740. (SCI, IF=4.018) (co-PI, co-corresponding author). [Article featured on]

6. T.-Y. Chen, T.-L. Hwang, C.-Y. Lin, T.-N. Lin, H.-Y. Lai, W.-P. Tsai, H.-H. Lin* 2011 EMR2 receptor ligation modulates cytokine secretion profiles and cell survival of LPS-treated neutrophil. Chang Gung Medical Journal 34(5): 468-477. (corresponding author) (100年度長庚醫誌優秀論文獎貳獎)


7. H.-H. Lin and S. Gordon 2012 Chapter 1: Macrophage phenotype in tumours. In T. Lawrence and T. Hagemann (eds.) Tumour-Associated Macrophages. page 3-16, Springer Science+Business Media, LLC (Invited book chapter).

8. H.-H. Lin* 2012 Adhesion family of G protein-coupled receptors and cancer. Chang Gung Medical Journal 35(1): 15-27. (invited review) (corresponding author).

9. Y.-S. Huang, N.-Y. Chiang, C.-H. Hu, C.-C. Hsiao, K.-F. Cheng, W.-P. Tsai, Simon Yona, Martin Stacey, Siamon Gordon, G.-W. Chang* and H.-H. Lin* 2012 Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol. Cell. Biol. 32(8): 1408-1420 (SCI, IF=4.398) (co-first and co-corresponding author)

10. H.-H. Lin* and M.-L. Kuo 2012 News and Perspectives: The 2011 Nobel Prize in Physiology or Medicine. Chang Gung Medical Journal 35(2): 93-95. (invited review) (co-first and co-corresponding author)

11. J. Hamann and H.-H. Lin 2012 "EGF-TM7 receptors", In Gordon, S. (ed.), Macrophage Heterogeneity and Function, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at

12. D. Araç, G. Aust, D. Calebiro, F. B. Engel, C. Formstone, A. Goffinet, J. Hamann, R. J. Kittel, I. Liebscher, H.-H. Lin, K. R. Monk, A. Petrenko, X. Piao, S. Prömel, H. B. Schiöth, T. W. Schwartz, M. Stacey, Y. A. Ushkaryov, M. Wobus, U. Wolfrum, L. Xu, and T. Langenhan 2012 Dissecting signaling and functions of adhesion G protein-coupled receptors. Ann. N. Y. Acad. Sci. 1276: 1-25. (SCI, IF=4.706)


13. H.-H. Lin* 2013 Chapter 8, Autoproteolytic cleavage of adhesion-GPCRs at the GPCR proteolysis site: molecular mechanism, structure and functional significance. In Leon V. Berhardt (ed.) GPCRs: Molecular Pharmacology, Drug Targeting and Signaling Regulation. Advances in Medicine and Biology 60: 199-210. Nova Science Publishers, Inc. (invited book chapter)

14. W.-Y. Tseng, Y.-S. Huang, N.-Y. Chiang, Y.-P. Chou, Y.-J. Jan Wu, S.-F. Luo, C.-F. Kuo, K.-M. Lin, H.-H. Lin* 2013 Increased soluble CD4 in serum of rheumatoid arthritis patients is generated by matrix metalloproteinase (MMP)-like proteinases. PLoS ONE 8(5): e63963. (SCI, IF=2.806) (corresponding author)

15. H.-H. Lin* 2013 G protein-coupled receptors and their (bio)chemical significance win 2012 Nobel Prize in Chemistry. Biomedical Journal 36(3): 118-124. (corresponding author)


16. C.-C. Hsiao&, W.-C. Wang&, W.-L. Kuo, H.-Y. Chen, T.-C. Chen, J. Hamann, H.-H. Lin* 2014 CD97 inhibits cell migration in human fibrosarcoma cells by modulating TIMP-2/MT1-MMP/MMP-2 activity. FEBS Journal 281(21):4878-91. (doi:10.1111/febs.13027) (SCI, IF=3.902) (corresponding author)

17. I. Liebscher, B. Ackley, D. Araç, D. M. Ariestanti, G. Aust, Byoung-il Bae, B. R. Bista, J. P. Bridges, J. G. Duman, F. B. Engel, S. Giera, A. M. Goffinet, R. A. Hall, J. Hamann, N. Hartmann, Hsi-Hsien Lin, Mingyao Liu, Rong Luo, A. Mogha, K. R. Monk, M. C. Peeters, S. Prömel, S. Ressl, H. B. Schiöth, S. M. Sigoillot, H. Song, W. S. Talbot, G. G. Tall, J. P. White, U. Wolfrum, Lei Xu, and Xianhua Piao  2014 New functions and signaling mechanisms for the class of Adhesion G protein-coupled receptors. Ann. N. Y. Acad. Sci. 1333: 43-64. (SCI, IF=4. 706)


18. J. Hamann, G. Aust, D. Araç, F. B. Engel, C. Formstone, R. Fredriksson, B. L. Harty, C. Kirchhoff, B. Knapp, A. Krishnan, I. Liebscher, H.-H. Lin, D. C. Martinelli, K. R. Monk, M. C. Peeters, X. Piao, S. Prömel, T. Schöneberg, T. W. Schwartz, K. Singer, M. Stacey, Y. A. Ushkaryov, M. Vallon, U. Wolfrum, M. W. Wright, L. Xu, T. Langenhan, H. B. Schiöth 2015 International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein-Coupled Receptors. Pharmacological Reviews 67(2):338-367. (SCI, IF=17.893)

19. T.-Y. Yang, N.-Y. Chiang, W.-Y. Tseng, H.-L. Pan, Y.-M. Peng, J.-J. Shen, K.-A. Wu, M.-L. Kuo, G.-W. Chang, H.-H. Lin* 2015 Expression and immunoaffinity purification of recombinant soluble human GPR56 protein for the analysis of GPR56 receptor shedding by ELISA. Protein Expression and Purification 109:85-92 (SCI, IF=1.351) (corresponding author)

20. C.-C. Hsiao&, K. Keysselt&, H.-Y. Chen, D. Sittig, J. Hamann, H.-H. Lin*, G. Aust* 2015 The Adhesion-GPCR CD97/ADGRE5 inhibits apoptosis. The International Journal of Biochemistry & Cell Biology 65:197-208 (SCI, IF=3.505) (co-corresponding author)

21. H.-H. Lin* 2015 Tumor-associated adhesion-class G protein-coupled receptors. Adaptive Medicine 7(4): 175-185. (invited review) (corresponding author)


22. N.-Y. Chiang, G.-W. Chang, Y.-S. Huang, Y.-M. Peng, C.-C. Hsiao, M.-L. Kuo, H.-H. Lin* 2016 Heparin interacts with adhesion-GPCR GPR56/ADGRG1, reduces receptor shedding, and promotes cell adhesion and motility. J. Cell Sci. 129:2156-2169 (SCI, IF=4.431) (corresponding author)

23.Cheng-Jang Wu, Chun-Hao Lu, Li-Chen Chen, Duc T. Nguyen, Yi-Shu Huang, Hsi-Hsien Lin, Chun-Yen Lin, Ming-Ling Kuo 2016 CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities Biochemical and Biophysical Research Communications (accepted) (SCI, IF=2.466).

24. G.-W. Chang&, C.-C. Hsiao&, Y.-M. Peng, F.A. Vieira Braga, N.A.M. Kragten, E.B.M. Remmerswaal, M.D.B. van de Garde, R. Straussberg, G. M. König, E. Kostenis, V. Knäuper, L. Meyaard, René A.W. van Lier, K.P. van Gisbergen, H.-H. Lin*, J. Hamann* 2016 The adhesion G protein-coupled receptor GPR56/ADGRG1 is an inhibitory receptor on human NK cells. Cell Reports 15:1757-1770 (SCI, IF=8.282) (co-corresponding author)(This article was recommended in F1000Prime as being of special significance in its field by F1000 Faculty Member Jacques Zimmer)

25. H.-H. Lin*, M. Stacey* 2016 G protein-coupled receptors in myeloid cells. Microbiology Spectrum Aug. 2016, 4(4) doi:10.1128/microbiolspec. MCHD-0028-2016 (co-corresponding author)

26. Matthias Nieberler, Robert J. Kittel, Alexander G. Petrenko, Hsi-Hsien Lin*, Tobias Langenhan* 2016 Control of Adhesion GPCR function through proteolytic processing. (invited chapter) Handbook of Experimental Pharmacology 234:83-109 (co-corresponding author)

27. Jörg Hamann*, Cheng-Chih Hsiao, Kodi Ravichandran, and Hsi-Hsien Lin* 2016 Adhesion GPCRs as modulators of immune cell function. (invited chapter) Handbook of Experimental Pharmacology 234: 329-350 (co-corresponding author)

28. Chien-Hao  Huang, Wen-Juei  Jeng, Yu-Pin  Ho, Wei Teng, Yi-Chung  Hsieh,Wei-Ting  Chen, Yi-Cheng Chen, Hsi-Hsien  Lin, I-Shyan  Sheen, and Chun-Yen Lin 2016 Increased EMR2 expression on neutrophils correlates with disease severity and predicts overall mortality in cirrhotic patients. Sci. Rep. 6, 38250; doi: 10.1038/srep38250 (SCI, IF=4.259)


29.  Nien-Yi Chiang&, Yen-Ming Peng&, Horng-Heng Juang, Tse-Ching Chen, Hsiao-Lin Pan, Gin-Wen Chang, Hsi-Hsien Lin# 2017 GPR56/ADGRG1 activation promotes melanoma cell migration via NTF dissociation and CTF-mediated Gα12/13/RhoA signaling. J. Inv. Dermatol. 137:727-736 (corresponding author) (SCI, IF=6.287)

30. Kuan-Yu I, Yi-Shu Huang, Ching-Hsun Hu, Wen-Yi Tseng, Chia-Hsin Cheng, Martin Stacey, Siamon Gordon, Gin-Wen Chang, Hsi-Hsien Lin* 2017 Activation of EMR2/ADGRE2 induces macrophage differentiation and inflammatory responses via G16/Akt/MAPK/NF-B signaling pathways. Frontiers in Immunology April 3; 8:373 (corresponding author) (SCI, IF=6.429)

31. Wen-Yi Tseng, I-Shu Huang, Hsi-Hsien Lin, Shue-Fen Luo, Kay McNamee, Felix Clanchy, Richard Williams 2017 TNFR1 and TNFR2 signalling and its clinical implications. Cytokine (SCI, IF=3.488) (published online 26 October 2016) (

32. Wen-Yi Tseng, Yeong-Jian Jan Wu, Tai-Yun Yang, Nien-Yi Chiang, Wen-Pin Tsai, Siamon Gordon, Gin-Wen Chang, Chang-Fu Kuo, Shue-Fen Luo*, Hsi-Hsien Lin* 2017 High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis. Journal of Microbiology, Immunology and Infection (accepted) (co-corresponding author) (SCI, IF=2.973)

33. Hsi-Hsien Lin*, Cheng-Chih Hsiao, Caroline Pabst, Josée Hébert, Torsten Schöneberg and Jörg Hamann* 2017 Adhesion GPCRs in regulating immune responses and inflammation. Advances in Immunology (co-corresponding author) (2015 SCI, IF=7.064)

34.  Kuo-An Wu#, Chih-Ching Wu#, Chi-De Chen, Chi-Ming Chu, Li-Jane Shih, Yu-Ching Liu, Chia-Jung Yu, Hsi-Hsien Lin*, Chia-Yu Yang* 2017 Proteome profiling reveals novel biomarkers to identify parapneumonic effusions. Sci. Rep. (SCI, IF=4.259) (co-corresponding author)



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