Faculty

 

박석희 (Seok Hee Park) 직함 전공 연구실 전화 사무실 이메일    교수 분자세포생물학 세포성장조절연구실 031-290-5912 제2과학관 32366 parks@skku.edu

 연구실 소개                                                                                                                                                                                                   

○ 연구 분야: 세포는 정교한 신호 전달 체계 안에서 각자 자기가 맡은 역할을 하고 있습니다. 많은 질병들이 이러한 신호 전달 체계의 문제로 인해 발생하는 경우가 많습니다. 우리 연구실에서는 다양한 질병(Cancer, Lung disease 등) 모델, 다양한 cell line에서 나타나는 신호 전달 체계를 단백질 수준에서 연구하고 있습니다. 특히, 신호 전달 체계 조절에 중요하다고 알려진 단백질의 post-translational modification(PTM)에 초점을 맞춰 단백질의 phosphorylation, ubiquitination을 중점적으로 연구하고 있습니다.

 

○ 응용 분야: 특정 질병에 중요하게 관여하는 세포 신호 전달 체계의 새로운 조절 기작을 밝혀낸다는 것은 그 질병을 치료하는데 있어 새로운 치료 타겟을 제시할 수 있음을 의미합니다. 실제로 우리 연구실에서는 대장염을 조절하는 새로운 치료 타겟 단백질을 찾았고 이를 이용하여 약으로 사용할 수 있는 물질을 개발, 현재 벤처 회사에 기술 이전하여 회사에서 임상 중에 있습니다.

 

○ 졸업생 취업 분야

▶삼성 바이오에피스	▶일동제약
▶LG 화학	▶한국 콜마
▶STGEN BIO	▶Bridgebio Therapeutics
▶GO Biolabs

 Research Background                                                                                                                                                                                     

1) Tumor microenvironment에서 면역세포와 암세포의 상호작용 분석

Tumor microenvironment (종양 미세 환경)는 종양과 그 주위의 수많은 세포와 조직 그리고 단백질을 아울러 총칭합니다. 암세포는 생존을 위해 주위의 환경을 본인의 성장에 유리하게 조정하며 이를 통해 영양과 산소를 공급받고 immune evasion (면역회피)를 유도합니다. 이는 암 치료의 큰 장벽으로 작용하여 이를 해결하기 위한 여러 노력들이 이루어지고 있고 최근 10년 동안 immunotherapy가 각광받는 이유입니다. 우리 연구실은 암세포의 immune evasion 기전을 신호 전달 체계를 중심으로 분석하고 주요 단백질의 post-translational modification에 의한 조절에 초점을 맞추어 면역세포와 암세포의 상호작용을 분석하고 있습니다.

2) Organ specific disease에서 특정한 단백질의 중요성과 역할 규명

우리가 겪는 여러가지 질병들은 주로 특정 장기의 기능이 손상되었을 때 발생합니다. 질병은 환경적인 요인과 유전적인 요인에 의해 발생할 수 있습니다. 질병의 발생은 환경적인 요인과 유전적인 요인, 혹은 동시에 같이 작용할 수 있습니다. 특히 같은 환경에 노출되더라도 유전적 요인에 의해 질병의 발생과 진행은 전혀 다른 양상을 보일 수 있습니다. 본 연구실은 Cre-loxp system을 통해 특정 조직에 특정 유전자가 발현되지 않는 tissue-specific knockout mouse를 여러 종류 확보하고 있고, 각 mouse에서 여러가지 질병 모델을 만들어 연구하고 있습니다. 이를 통해 특정 조직에서 유전자가 만들어내는 단백질이 질병의 주된 신호전달 체계에 어떤 방식으로 작용하는지 분석하고 있습니다.

 

  

 

 Research Interests                                                                                                                                                                                         

○ Cancer immunology in cancer microenvironment

○ Regulation of signaling pathway in organ-specific disease

 Education and experience                                                                                                                                                                               

2013                Professor, Dept.of Biological Sciences, Sungkyunkwan University

2007 - 2013       Associate Professor, Dept.of Biological Sciences, Sungkyunkwan University

2003 - 2007       Assistant Professor, College of Medicine Inha University

2001 - 2003       Senior Research Investigator, National Cancer Center, Korea

1998 - 2001       Postdoc, National Cancer Institute, NIH (USA)

1998                Ph.D., Dept. of Microbiology, SeoulNational University

1991                M.S., Dept. of Microbiology, SeoulNational University

1989                B.S., Dept. of Microbiolgy, SeoulNational University

 

 Lecture                                                                                                                                                                                                        

○ 분자생물학 (Molecular Biology): 학부생 대상

○ 감염반응생물학 (Infection Response Biology): 학부생 대상

○ 유전공학 (Genetic Engineering): 학부생 대상

○ 분자암학(Molecular Cancer Biology): 대학원 대상 

○ 의과학연구방법론(Experimental Medical Sciences): 대학원 대상

 

 Key Publications                                                                                                                                                                                           

1. Ha, J., Kim, M., Seo, D.,Park, J. S., Lee, J., Lee, J., Park, S. H.* (2020) The Deubiquitinating EnzymeUSP20 Regulates the TNFα-Induced NF-κB Signaling Pathway through Stabilizationof p62. Int J Mol Sci. 21(9), 3116. doi: 10.3390/ijms21093116

2. Seo, D., Jung, S. M., Park,J. S., Lee, J., Ha, J., Kim, M., Park, S. H.* (2019) The deubiquitinatingenzyme PSMD14 facilitates tumor growth and chemoresistance through stabilizingthe ALK2 receptor in the initiation of BMP6 signaling pathway. EBioMedicine,49, 55–71. doi: 10.1016/j.ebiom.2019.10.039

3. Park, J. S., Kim, M., Song,N. J., Kim, J. H., Seo, D., Lee, J. H., Jung, S. M., Lee, J. Y., Lee, J., Lee,Y. S., Park, K. W., Park, S. H.* (2019) A Reciprocal Role of the Smad4-Taz Axisin Osteogenesis and Adipogenesis of Mesenchymal Stem Cells. Stem cells, 37(3),368–381. doi: 10.1002/stem.2949

4. Kim, J.H., Seo, D., Kim,S.J., Choi, D.W., Park, J.S., Ha, J.H., Choi, J.W., Lee, J.H., Jung, Seo, K.W.,Lee, E.W., Lee, Y.S., Cheong, H.S, Choi, C.Y., Park S.H.* (2018) Thedeubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagyinitiation. EMBO Rep. Apr;19(4):e44378. doi: 10.15252/embr.201744378

5. Lee, J. H., Jung, S. M.,Yang, K. M., Bae, E., Ahn, S. G., Park, J. S., Seo, D., Kim, M., Ha, J., Lee,J., Kim, J. H., Kim, J. H., Ooshima, A., Park, J., Shin, D., Lee, Y. S., Lee,S., van Loo, G., Jeong, J., Kim, S. J., … Park, S. H.* (2017) A20 promotesmetastasis of aggressive basal-like breast cancers through multi-monoubiquitylationof Snail1. Nat Cell Biol. 19(10), 1260–1273. doi: 10.1038/ncb3609

6. Lee, J. Y., Seo, D., You,J., Chung, S., Park, J. S., Lee, J. H., Jung, S. M., Lee, Y. S., Park, S. H.*(2017) The deubiquitinating enzyme, ubiquitin-specific peptidase 50, regulatesinflammasome activation by targeting the ASC adaptor protein. FEBS Lett.591(3), 479–490. doi: 10.1002/1873-3468.12558

7. Park, J. S., Yi, T. G.,Park, J. M., Han, Y. M., Kim, J. H., Shin, D. H., Tak, S. J., Lee, K., Lee, Y.S., Jeon, M. S., Hahm, K. B., Song, S. U., Park, S. H.* (2015) Therapeuticeffects of mouse bone marrow-derived clonal mesenchymal stem cells in a mousemodel of inflammatory bowel disease. Journal of clinical J Clin Biochem Nutr.57(3), 192–203. doi: 10.3164/jcbn.15-56

8. Lee, Y. S., Park, J. S.,Jung, S. M., Kim, S. D., Kim, J. H., Lee, J. Y., Jung, K. C., Mamura, M., Lee,S., Kim, S. J., Bae, Y. S., Park, S. H.* (2015) Inhibition of lethalinflammatory responses through the targeting of membrane-associated Toll-likereceptor 4 signaling complexes with a Smad6-derived peptide. EMBO Mol Med.7(5), 577–592. doi: 10.15252/emmm.201404653

9. Jung, S.M., Lee, J.H.,Park, J., Oh, Y.S., Lee, S.K., Park, J.S., Lee, Y.S., Kim, J.H., Lee, J.Y.,Bae, Y.S., Koo, S.H., Kim, S.J., Park, S.H.* (2013) Smad6 inhibitsnon-canonical TGF-beta1 signalling by recruiting the deubiquitinase A20 toTRAF6. Nat. Commun. Oct 7;4:2562. doi: 10.1038/ncomms3562.

10. Lee, H.J., Kim, J.H., Kim,J.H., Martinus, R.D., Park, S.H. (2013) Angiopoietin-like protein 2, a chronicinflammatory mediator, is a new target induced by TGF-β1 through aSmad3-dependent mechanism. Biochem. Biophys. Res. Commun.430:981- 986

11. Lee, Y.S., Park, J.S., Kim,J.H., Jung, S.M., Lee, J.Y., Kim, S.J., and Park, S.H.* (2011) Smad6-specificrecruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 inTLR4 signalling. Nat. Commun. 2:460. doi:10.1038/ncomms1469.

12. Kim, J.H., Sung, K.S.,Jung, S.M., Lee, Y.S., Kwon, J.Y., Choi, C.Y., and Park, S.H.* (2011)Pellino-1, an adaptor protein of interleukin-1 receptor/toll-like receptorsignaling, is sumoylated by Ubc9. Mol Cells. 31(1):85-89.

13. Lee, Y.S., Kim, J.H., Kim,S.T., Kwon, J.Y., Hong, S., Kim, S.J., and Park, S.H.* (2010) Smad7 and Smad6bind to discrete regions of Pellino-1 via their MH2 domains to mediateTGF-beta1-induced negative regulation of IL-1R/TLR signaling. Biochem. Biophys.Res. Commun.393:836-843

14. Lee, E.K., Jeon, W.K.,Chae, M.Y., Hong, H.Y., Lee, Y.S., Kim, J.H., Kwon, J.Y., Kim, B.C., and Park,S.H.* (2010) Decreased expression of glutaredoxin 1 is required fortransforming growth factor-beta1-mediated epithelial-mesenchymal transition ofEpRas mammary epithelial cells. Biochem. Biophys. Res. Commun.391:1021-1027

15. Lee, E.K., Lee, Y.S., Lee,H., Choi, C.Y., and Park, S.H.* (2009) 14-3-3epsilon protein increases matrixmetalloproteinase-2 gene expression via p38 MAPK signaling in NIH3T3 fibroblastcells. Exp. Mol. Med. 41:453-461

16. Lee, Y.S., Lee, E.K., Han,I.O., and Park, S.H.* (2008) Etoposide-induced Smad6 expression is required forthe G1 to S phase transition of the cell cycle in CMT-93 mouse epithelialcells. Exp. Mol. Med. 40:43-51       

17. Choi. K.-C., Lee, Y.S., Lim, S., Choi, H.K.,Lee, C.-H., Lee, E.-K., Hong, S., Kim, I.-H., Kim, S.-J., and Park, S.H.*(2006) Smad6 negatively regulates interleukin-1 receptor-Toll-like Receptorsignaling through direct interaction with the adaptor Pellino-1. Nature Immunol.7:1057-65

18. Ju, E.M., Choi, K.-C.,Hong, S.-H., Lee, C.-H., Kim, B.-C., Kim, S.-J., Kim, I.-H., and Park, S.H.*(2005) Apoptosis of Mink lung epithelial cells by co-treatment of low-doseStaurosporine and Transforming Growth Factor-b1 depends on the enhanced TGF-bsignaling and requires the decreased phosphorylation of PKB/Akt. Biochem.Biophys. Res. Commun. 328:1170-1181.       

19. Choi, K-.C., Lee, S., Kwak,S.Y., Kim, M-.S., Choi, H.K., Kim, K.H., Chung, J.H., and Park, S.H.* (2005)Increased expression of 14-3-3e protein in intrinsically aged and photoagedhuman skin in vivo. Mech. Age. Dev. 126: 629-636 

20. Park, S.H.* (2005) Finetuning and cross-talking of TGF-beta signal by inhibitory Smads. J. Biochem.Mol. Biol. 38(1):9-16       

 

 Co-work publications                                                                                                                                                                                     

1.  Jung,J., Baek, J., Tae, K., Shin, D., Han, S., Yang, W., Yu, W., Jung, S. M., Park,S. H., Choi, C. Y., Lee, S. (2022) Structural mechanism for regulation of Rab7by site-specific monoubiquitination. Int J Biol Macromol. 194, 347–357. doi:10.1016/j.ijbiomac.2021.11.074

2.  Kim,J., Shin, J. W., Lee, H. J., Kim, J. H., Choi, S. M., Lee, C. H., Kang, H. R.,Park, S. H., Bae, Y. S., Chung, D. H., Kim, H. Y. (2021) Serum amyloid Apromotes emphysema by triggering the reciprocal activation of neutrophils andILC3s. Clin Transl Med. 11(12), e637. doi: 10.1002/ctm2.637

3.  Yoon,C. I., Ahn, S. G., Cha, Y. J., Kim, D., Bae, S. J., Lee, J. H., Ooshima, A.,Yang, K. M., Park, S. H., Kim, S. J., Jeong, J. (2021) Metastasis RiskAssessment Using BAG2 Expression by Cancer-Associated Fibroblast and TumorCells in Patients with Breast Cancer. Cancers (Basel)., 13(18), 4654. doi:10.3390/cancers13184654

4.  Kim,G. Y., Jeong, H., Yoon, H. Y., Yoo, H. M., Lee, J. Y., Park, S. H., Lee, C. E.(2020) Anti-inflammatory mechanisms of suppressors of cytokine signaling targetROS via NRF-2/thioredoxin induction and inflammasome activation in macrophages.BMB rep. 53(12), 640–645. doi: 10.5483/BMBRep.2020.53.12.161

5.  Jeon,J., Noh, H. J., Lee, H., Park, H. H., Ha, Y. J., Park, S. H., Lee, H., Kim, S.J., Kang, H. C., Eyun, S. I., Yang, S., Kim, Y. S. (2020) TRIM24-RIP3 axisperturbation accelerates osteoarthritis pathogenesis. Ann Rheum Dis. 79(12),1635–1643. doi: 10.1136/annrheumdis-2020-217904

6.  Hong,E., Park, S., Ooshima, A., Hong, C. P., Park, J., Heo, J. S., Lee, S., An, H.,Kang, J. M., Park, S. H., Park, J. O., Kim, S. J. (2020) Inhibition of TGF-βsignalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorinsuppresses invasion and prolongs survival in pancreatic tumour mouse models.Sci rep. 10(1), 2935. doi: 10.1038/s41598-020-59893-5

7.  Yoon,C. I., Ahn, S. G., Bae, S. J., Shin, Y. J., Cha, C., Park, S. E., Lee, J. H.,Ooshima, A., Lee, H. S., Yang, K. M., Kim, S. J., Park, S. H., Jeong, J. (2019)High A20 expression negatively impacts survival in patients with breast cancer.PLoS one, 14(8), e0221721. doi: 10.1371/journal.pone.0221721

8.  Park,J. E., Park, J. S., Jang, S. Y., Park, S. H., Kim, J. W., Ki, C. S., Kim, D. K.(2019). A novel SMAD6 variant in a patient with severely calcified bicuspidaortic valve and thoracic aortic aneurysm. Mol Genet Genomic Med., 7(5), e620.doi: 10.1002/mgg3.620

9.  Yang,K. M., Bae, E., Ahn, S. G., Pang, K., Park, Y., Park, J., Lee, J., Ooshima, A.,Park, B., Kim, J., Jung, Y., Takahashi, S., Jeong, J., Park, S. H., Kim, S. J.(2017) Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B inTriple-Negative Breast Cancer Cells. Cell rep. 21(10), 2952–2964. doi:10.1016/j.celrep.2017.11.026

10.  Shin,D., Na, W., Lee, J. H., Kim, G., Baek, J., Park, S. H., Choi, C. Y., Lee, S.(2017). Site-specific monoubiquitination downregulates Rab5 by disruptingeffector binding and guanine nucleotide conversion. eLife, 6, e29154. doi:10.7554/eLife.29154

11.  YoonJH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, KimOH, Oh BC, Sumida T, Kuroda M, Ju JH, Jung KC, Park SH, Kim DK, Mamura M.Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitindegradation of Smad4, thereby derepressing eomesodermin in cytotoxic Tlymphocytes. (2013) EMBO Mol. Med. 5(11):1720-39

12.  Lim,S., Bae, E., Kim, H.S., Kim, T.A., Byun, K., Kim, B., Hong, S., Im, J.P., Yun,C., Lee, B., Lee B, Park, S.H., Letterio, J., Kim, S.J. (2012) TRAF6 mediatesIL-1β/LPS-induced suppression of TGF-β signaling through its interaction withthe type III TGF-β receptor. PLoS One 7(3):e32705

13.  Kang,Y.J.,Shin, J.W., Yoon, J.H., Oh, I.H., Lee, S.P., Kim, S.Y., Park, S.H., Mamura, M. (2012)Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stemcells. Biochem. Biophys. Res. Commun.423:750-756

14.  Kang,H.S., Lee, S.C., Park, Y.S., Jeon, Y.E., Lee, J.H., Jung, S.Y., Park, I.H.,Jang, S.H., Park, H.M., Yoo, C.W., Park, S.H., Han, S.Y., Kim, K.P., Kim, Y.H.,Ro, J., and Kim, H.K. (2011) Protein and lipid MALDI profiles classify breastcancers according to the intrinsic subtype. BMC Cancer 11:465

15.  Kim,S.J., Shin, J.Y., Lee, K.D., Bae, Y.K., Choi, I.J., Park, S.H., and Chun, K.H.(2011) Gallectin-3 facilitates cell motility in gastric cancer by up-regulatingProtease-Activated Receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1).PLoS ONE  6(9): e25103.doi:10.1371/journal.pone.0025103

16.  Kim,S.J., Shin, J.Y., Cheong, T.C., Choi, I.J., Lee, Y.S., Park, S.H., and Chun,K.H. (2011) Galectin-3 germline variant at position 191 enhances nuclearaccumulation and activation of β-catenin in gastric cancer Clin Exp Metastasis.

17.  Kim,S.J., Choi, I.J., Cheong, T.C., Lee, S.J., Lotan, R., Park, S.H., and Chun,K.H. (2010) Galectin-3 increases gastric cancer cell motility by up-regulatingfascin-1 expression. Gastroenterology 138:1035-1045

18.  Hong,J.H., Lee, G.T., Lee, J.H., Kwon, S.J., Park, S.H., Kim, S.J., and Kim, I.Y.2009. Effect of bone morphogenetic protein-6 on macrophages. Immunology128:e442-450

19.  Lee,E.K., Lee, Y.S., Lee, H., Choi, C.Y., and Park, S.H.* 2009. 14-3-3epsilonprotein increases matrix metalloproteinase-2 gene expression via p38 MAPKsignaling in NIH3T3 fibroblast cells. Exp. Mol. Med. 41:453-461

20.  Ryu,J.K., Piao, S., Shin, H.Y., Choi, M.J., Zhang, L.W., Jin, H.R., Kim, W.J., Han,J.Y., Hong, S.S., Park, S.H., Lee, S.J., Kim, I.H., Lee, C.R., Kim, D.K.,Mamura, M., Kim, S.J., and Suh, J.K. (2009) IN-1130, a novel transforminggrowth factor-beta type I receptor kinase (activin receptor-like kinase 5)inhibitor, promotes regression of fibrotic plaque and corrects penile curvaturein a rat model of Peyronie's disease. J. Sex. Med. 6:1284-1296

21.  Lee,H., Kwak, H.J., Cho, I.T., Park, S.H., and Lee, C.H. (2009) S1219 residue of53BP1 is phosphorylated by ATM kinase upon DNA damage and required for properexecution of DNA damage response. Biochem Biophys Res Commun. 378:32-36       

22.  Zhang,L.W., Piao, S., Choi, M.J., Shin, H.Y., Jin, H.R., Kim, W.J., Song, S.U., Han,J.Y., Park, S.H., Mamura, M., Kim, S.J., Ryu, J.K., and Suh, J.K. (2008) Roleof increased penile expression of transforming growth factor-beta1 andactivation of the Smad signaling pathway in erectile dysfunction in streptozotocin-induceddiabetic rats. J. Sex. Med. 5:2318-2329       

23.  Lee,S.A., Park, S.H. and Kim, B.C. (2008) Raloxifene, a selective estrogen receptormodulator, inhibits lipopolysaccharide-induced nitric oxide production byinhibiting the phosphatidylinositol 3-kinase/Akt/nuclear factor-kappa B pathwayin RAW264.7 macrophage cells. Mol. Cells 26:48-52       

24.  Piao,S., Ryu, J.K., Shin, H.Y., Zhang, L., Song, S.U., Han, J.Y., Park, S.H., Kim,J.M., Kim, I.H., Kim, S.J., and Suh, J.K. (2008) Repeated intratunicalinjection of adenovirus expressing transforming growth factor-beta1 in a ratinduces penile curvature with tunical fibrotic plaque: a useful model for thestudy of Peyronie's disease. Int. J. Androl. 31: 346-353       

25.  Lee,E.K., Lee, Y.S., Han, I.O., and Park, S.H.* (2007) Expression of Caveolin-1reduces cellular responses to TGF-beta1 through down-regulating the expressionof TGF-beta type II receptor gene in NIH3T3 fibroblast cells. Biochem BiophysRes Commun. 359:385-390       

26.  Hong,S., Lim, S., Li, A.G., Lee, C. Lee, Y.S. Lee, E.-K., Park, S.H., Wang, X.-J.,and Kim, S.-J. (2007) Smad7 binds to the adaptors TAB2 and TAB3 to blockrecruitment of the kinase TAK1 to the adaptor TRAF2. Nature Immunol. 8:504-513       

27.  Jung,J.W. Hwang, S.Y., Hwang, J.S., Oh, E.S., Park, S.H., and Han, I.O. (2007)Ionising radiation induces changes associated with epithelial-mesenchymaltransdifferentiation and increased cell motility of A549 lung epithelial cells.Eur. J. Cancer. 43:1214-1224       

28.  Ku,J.-L., Park, S.H., Yoon, K.-A., Shin, Y.-K., Kim, K.-H., Choi, J.-S., Kang,H.-C., Kim, I.-J., Han, I.-O., and Park, J.-G. (2007) Genetic alterations ofthe TGF-β signaling pathway in colorectal cancer cell lines: A novel mutationin Smad3 associated with the inactivation of TGF-β-induced transcriptionalactivation. Cancer Lett. 247:283-92.         

29.  Kwak,H., Kim, S.H., Yoo, H.G., Park, S.H., and Lee, C.-H. (2005) Jun activationdomain-binding protein 1 is required for hyperphosphorylation of 53BP1 uponmitotic checkpoint activation. J. Cancer Biol. Clin. Oncol. 131:789-96.        

 

 Lab member                                                                                                                                                                                                 

	김민범 (Minbeom Kim)
	학위과정	석박통합과정
	연구실	세포성장조절연구실
	이메일	minbum@skku.edu
	연구주제	Function of deubiquitinase in apoptosis pathway.