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Hsi-Hsien Lin

Appointment: Associate Professor

LabMolecular Immunology

Education: Ph.D.

University/NationUniversity of Tennessee/U.S.A.

Tel: 3321

E-mail: hhlin@mail.cgu.edu.tw

Research website: https://sites.google.com/site/hhlinlab/

Laboratory personnel:

Postdoctoral fellow:1 ; Ph.D. student:1 ; Master student:1 ; Res. Assistant:5 ; ndergraduate:1

Research interests:

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.



 *: corresponding author; &: co-first author

1. 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)


2. 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=2.766) (corresponding author)


3. 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)

4. 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. (SCI, IF=4.530) (corresponding author)

5. 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, H.-H. 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=4.277)


6.  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=18.964)

7. 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=1.338) (corresponding author)

8. 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=3.247) (co-corresponding author)


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


10. C.-J. Wu, C.-H. Lu, L.-C. Chen, D. T. Nguyen, Y.-S. Huang, H.-H. Lin, C.-Y.Lin, M.-L. 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 473:973-979 (SCI, IF=2.559).


11. 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=4.401) (corresponding author)

12. 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=8.032) (co-corresponding author)


13. 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)


14. 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)


15. Jörg Hamann*, Cheng-Chih Hsiao, Chang-Sup Lee, 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)


16. 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=4.122)


17. 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 (SCI, IF=6.448) (corresponding author)


18. 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 Ga16/Akt/MAPK/NF-kB signaling pathways. Frontiers in Immunology  8:373   (doi:10.3389/fimmu.2017.00373) (SCI, IF=5.511) (corresponding author)


19.  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. 7 (1): 4026 (doi:10.1038/s41598-017-04189-4)(SCI, IF=4.122) (co-corresponding author)


20. 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 136:163-201 (co-corresponding author) (SCI, IF=5.935)


21. Wen-Yi Tseng, I-Shu Huang, Hsi-Hsien Lin, Shue-Fen Luo, Kay McNamee, Felix Clanchy, Richard Williams 2018 TNFR1 and TNFR2 signalling and its clinical implications. Cytokine 101:19-25 (SCI, IF=3.514)


22. Yi-Shu Huang, Nien-Yi Chiang, Gin-Wen Chang, Hsi-Hsien Lin* 2018 Membrane-association of EMR2/ADGRE2-NTF is regulated by site-specific N-glycosylation. Sci. Rep. 8: 4532 (doi:10.1038/s41598-018-22849-x) (SCI, IF=4.122) (corresponding author)


23. Kuan-Yeh Huang and Hsi-Hsien Lin* 2018 The activation and signaling mechanisms of GPR56/ADGRG1 in melanoma cell. Frontiers in Oncology 8: 304 (doi:10.3389/fonc.2018.00304) (SCI, IF=4.416) (corresponding author)


24. 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* 2018 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 51(4):485-491 (co-corresponding author) (SCI, IF=2.094)


25. Cheng-Chih Hsiao#, Tai-Ying Chu#, Chia-Jung Wu, Maartje van den Biggelaar, Caroline Pabst, Josée Hébert, Taco W. Kuijpers, Brendon P. Scicluna, Kuan-Yu I, Tse-Ching Chen, Ines Liebscher, Jörg Hamann*, and Hsi-Hsien Lin* 2018 The adhesion G protein-coupled receptor GPR97/ADGRG3 is expressed in human granulocytes and triggers antimicrobial effector functions. Frontiers in Immunology 9: 2830  (doi:10.3389/fimmu.2018.02830) (SCI, IF=5.511) (co-corresponding author)

26. Wen-Ye Tjong and Hsi-Hsien Lin* 2019 The RGD motif is involved in CD97/ADGRE5-promoted cell adhesion and viability of HT1080 cells. Sci. Rep. (accepted) (SCI, IF=4.122) (corresponding author)









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