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허원기 Huh, Won-Ki

허원기
연구분야
미생물학 생화학 세포생물학 유전체학

단백질(protein)은 생체를 이루는 주요 구성성분일 뿐만 아니라 다양한 구조를 형성하여 여러 가지 생리 기능을 수행함으로써 생명 현상의 발현과 조절에 핵심적인 역할을 담당한다. 본 연구실은 여러 가지 기능유전체학(functional genomics) 및 단백체학(proteomics)적 방법을 사용하여 현대 생물학의 주요 연구모델인 효모(Saccharomyces cerevisiae)와 인간 세포주에서 세포 기능 조절과 관련된 단백질들을 새로이 발굴하고 분자 수준에서 그들의 작용 기전을 규명하는 것을 연구 목표로 삼고 있다. 또한 2013년 11월에 창업한 바이오벤처기업 (주)지피씨알(http://gpcr.co.kr)을 통해 환자맞춤형 항암치료제(personalized cancer therapeutics)를 개발함으로써 기초연구성과의 산업적 가치 발굴과 활용을 적극 추구하고자 한다.
   
1. Functional study of human GPCR heterodimers

GPCR (G-protein-coupled receptor)은 세포 외부로부터의 자극을 세포 내 신호전달경로로 매개해주는 세포 표면 수용체로서 인체의 주요 약물표적으로 작용한다. 최근에는 GPCR heterodimerization이 GPCR의 실질적인 기능 발현 및 조절에 매우 중요한 역할을 한다는 사실이 새로이 밝혀지고 있다. 본 연구에서는 GPCR heterodimerization 네트워크를 체계적으로 분석하고, heterodimerization에 의한 GPCR의 기능 조절 기전을 규명하며, 이를 바탕으로 GPCR heterodimer 기능 제어를 통한 질병 치료 방안을 탐구하고자 한다.

  (1) Identification of new GPCR heterodimers
  (2) Investigation of functional roles of GPCR heterodimerization
  (3) Development of drugs targeting GPCR heterodimers

2. Dissection of signaling pathways regulating cell growth, proliferation, and death

세포의 분열, 성장, 증식, 노화, 사멸은 가장 본질적인 생명 현상이다. 본 연구에서는 이 과정에 관여하는 TOR (target of rapamycin) signaling pathway, autophagy, rDNA (ribosomal DNA) silencing 등과 관련된 신규 조절 인자를 발굴하고 그 기능을 분석, 연구한다.

  (1) Analysis of TOR kinase interactome
  (2) Relationship between TOR signaling pathway and autophagy
  (3) Investigation of rDNA silencing factors

3. In vivo analysis of protein interaction network using BiFC assay

정교한 생명 현상의 발현 및 조절은 궁극적으로 세포 내 다양한 단백질들 간의 상호작용 네트워크를 통해 일어나게 된다. 따라서 생명 현상의 본질을 이해하기 위해선 단백질 상호작용 분석이 필수적이다. 본 연구에서는 살아있는 세포에서 단백질 상호작용을 직접 관측할 수 있는 BiFC (bimolecular fluorescence complementation) assay를 이용하여 유전체 수준(genome-wide level)에서 단백질 상호작용을 분석, 연구한다.

  (1) Development of platforms for genome-wide BiFC assay
  (2) Systematic analysis of human GPCR heterodimerization network
  (3) Global analysis of protein interaction network in yeast  

학력/경력
학력
  • - 1994.03 - 1998.08 박사: 서울대학교 미생물학과 (생물물리학 전공)
  • - 1992.03 - 1994.02 석사: 서울대학교 미생물학과 (생물물리학 전공)
  • - 1987.03 - 1992.02 학사: 서울대학교 미생물학과
경력
  • - 2023.06 - 현재 학부장, 서울대학교 생명과학부
  • - 2020.08 - 2023.06 소장, 서울대학교 미생물연구소
  • - 2013.11 - 현재 (주)지피씨알 공동창업자/CTO
  • - 2013.09 - 현재 교수, 서울대학교 생명과학부
  • - 2016.08 - 2019.02 부원장, 서울대학교 기초교육원
  • - 2014.10 - 2020.08 BK21플러스 생명과학고급인력양성사업단장
  • - 2012.11 - 2014.06 학생부학장, 서울대학교 자연과학대학
  • - 2010.02 - 2012.10 부학부장, 서울대학교 생명과학부
  • - 2008.09 - 2013.08 부교수, 서울대학교 생명과학부
  • - 2004.09 - 2008.08 조교수, 서울대학교 생명과학부
  • - 2001.03 - 2004.08 Postdoctoral Fellow, University of California-San Francisco
  • - 1998.09 - 2001.02 연수연구원, 서울대학교 분자미생물학연구센터
주요논문
  1. Hong , S., Kim, S.-K., Chung, C. H., Yun, C.-H., Lee, J., Cho, C.-S.*, and Huh, W.-K.* (2024) Pullulan nanoparticles inhibit the pathogenicity of Candida albicans by regulating hypha-related gene expression. Microbiol. Spectr. (In press)
  2. Jang, H.-S., Lee, Y., Kim, Y., and Huh, W.-K.* (2024) The ubiquitin-proteasome system degrades fatty acid synthase under nitrogen starvation when autophagy is dysfunctional in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 733:150423.
  3. Hong, S., Lee, H., and Huh, W.-K.* (2024) ARV1 deficiency induces lipid bilayer stress and enhances rDNA stability by activating the unfolded protein response in Saccharomyces cerevisiae. J. Biol. Chem. 300(5):107273.
  4. Liang, J., Seghiri, M., Singh, P. K., Seo, H. G., Lee, J. Y., Jo, Y., Song, Y. B., Park, C., Zalicki, P., Jeong, J.-Y., Huh, W.-K., Caculitan, N. G.*, Smith, A. W.* (2024) The β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells. Proc. Natl. Acad. Sci. U. S. A. 121(14):e2304897121.
  5. Choi, C., Bae, J., Kim, S., Lee, S., Kang, H., Kim, J., Bang, I., Kim, K., Huh, W.-K., Seok, C., Park, H., Im, W., Choi, H.J. (2023) Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family. Nat. Commun. 14(1):8105.
  6. Sukhtankar, D. D., Fung, J. J., Kim, M-n., Cayton, T., Chiou, V., Caculitan, N. G., Zalicki, P., Kim, S., Jo, Y., Kim, S., Lee, J. M., Choi, J., Mun, S., Chin, A., Jang, Y., Lee, J. Y., Kim, G., Kim, E. H., Huh, W.-K., Jeong, J.-Y., Seen, D.-S., Cardarelli, P. M.* (2023) GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol. PLoS One 18(10):e0287863.
  7. Hong, J. M., Lee, J.-W., Seen, D.-S., Jeong, J.-Y., and Huh, W.-K. (2023) LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration. Cell Commun. Signal. 21:257.
  8. Lee, Y., Kim, B., Jang, H.-S., and Huh, W.-K. (2023) Atg1-dependent phosphorylation of Vps34 is required for dynamic regulation of the phagophore assembly site and autophagy in Saccharomyces cerevisiae. Autophagy 19(9):2428-2442.
  9. Park, C., Lee, J.-W., Kim, K., Seen, D.-S., Jeong, J.-Y., and Huh, W.-K. (2023) Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration. Sci. Rep. 13:1894.
  10. Jung, S.-J., Yun, M., Yim, C., Hong, S., Huh, W.-K., and Kim, H. (2022) Expression level of Sec62 modulates membrane insertion of marginally hydrophobic segments. Biochim. Biophys. Acta, Biomembr. 1864(12):184051.
  11. Ramesh, R., Dautel, M., Lee, Y., Kim, Y., Storey, K., Gottfried, S., Goss Kinzy, T., Huh, W.-K., and Sattlegger, E. (2021) Asp56 in actin is critical for the full activity of the amino acid starvation-responsive kinase Gcn2. FEBS Lett. 595(14):1886-1901.
  12. Hong, S. and Huh, W.-K. (2021) Loss of Smi1, a protein involved in cell wall synthesis, extends replicative lifespan by enhancing rDNA stability in Saccharomyces cerevisiae. J. Biol. Chem. DOI: 10.1074/jbc.RA120.015456.
  13. Kim, B., Lee, Y., Choi, H., and Huh, W.-K. (2021) The trehalose-6-phosphate phosphatase Tps2 regulates ATG8 transcription and autophagy in Saccharomyces cerevisiae. Autophagy 17(4):1013-1027.
  14. Chang, Y., Lim, G., and Huh, W.-K. (2021) Analysis of the TORC1 interactome reveals spatially distinct function of TORC1 in mRNP complexes. J. Cell Biol. 220(4):e201912060.
  15. Lim, G., Chang, Y., and Huh, W.-K. (2020) Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle-specific activation of homologous recombination. Sci. Adv. 6(6):eaay2669.
  16. Singh, K., Lee, M. E., Entezari, M., Jung, C.-H., Kim, Y., Park, Y., Fioretti, J. D., Huh, W.-K., Park, H.-O., Kang, P. J. (2019) Genome-wide studies of Rho5-interacting proteins that are involved in oxidant-induced cell death in budding yeast. G3 (Bethesda). 9(3):921-931.
  17. Kim, Y., Jung, J. P., Pack, C.-G., and Huh, W.-K. (2019) Global analysis of protein homomerization in Saccharomyces cerevisiae. Genome Res. 29(1):135-145.
  18. Li, H.-M., Jang, J. H., Jung, J.-S., Shin, J., Park, C. O., Kim, Y.-J., Ahn, W.-G., Nam, J.-S., Hong, C.-W., Lee, J., Jung, Y.-J., Chen, J.-F., Ravid, K., Lee, H. T., Huh, W.-K., Kabarowski, J. H., and Song, D.-K. (2019) G2A protects mice against sepsis by modulating Kupffer cell activation: Cooperativity with adenosine receptor 2b. J. Immunol. 202(2):527-538.
  19. Yi, D.-G., Hong, S., and Huh, W.-K. (2018) Mitochondrial dysfunction reduces yeast replicative lifespan by elevating RAS-dependent ROS production by the ER-localized NADPH oxidase Yno1. PLoS One. 13(6):e0198619.
  20. Sing, T., Hung, M. P., Ohnuki, S., Suzuki G., San Luis, B.-J., McClain, M., Unruh, J., Yu, Z., Ou, J., Marshall-Sheppard, J., Huh, W.-K., Costanzo, M., Boone, C., Ohya, Y., Jaspersen, S., and Brown, G. (2018) The budding yeast RSC complex maintains ploidy by promoting spindle pole body insertion. J. Cell Biol. 217(7):2445-2462.
  21. Chang, Y., and Huh, W.-K. (2018) Ksp1-dependent phosphorylation of eIF4G modulates post-transcriptional regulation of specific mRNAs under glucose deprivation conditions. Nucleic Acids Res. 46(6):3047-3060.
  22. Choi, J.-H., Jeong, Y.-M., Kim, S., Lee, B., Ariyasiri K., Kim, H.-T., Jung, S.-H., Hwang, K.-S., Choi, T.-I., Park, C. O, Huh, W.-K., Carl, M., Rosenfeld, J. A., Raskin, S., Ma, A., Gecz, J., Kim, H.-G., Kim, J.-S., Shin, H.-C., Park, D.-S., Gerlai, R., Jamieson, B. B., Kim, J. S., Iremonger, K. J., Lee, S. H., Shin, H.-S., and Kim, C.-H. (2018) Targeted knockout of a chemokine-like gene increases anxiety and fear responses. Proc. Natl. Acad. Sci. U.S.A. 115(5):E1041-E1050.
  23. Lim, G., and Huh, W.-K. (2017) Rad52 phosphorylation by Ipl1 and Mps1 contributes to Mps1 kinetochore localization and spindle assembly checkpoint regulation. Proc. Natl. Acad. Sci. U.S.A. 114(44):E9261-E9270.
  24. So, Y. S., Yang, D. H., Jung, K. W., Huh, W.-K., and Bahn, Y. S. (2017) Molecular characterization of adenylyl cyclase complex proteins using versatile protein-tagging plasmid systems in Cryptococcus neoformans. J. Microbiol. Biotechnol. 27(2):357-364.
  25. Yi, D.-G., Kim, M. J., Choi, J. E., Lee, J., Jung, J., Huh, W.-K., and Chung, W.-H. (2016) Yap1 and Skn7 genetically interact with Rad51 in response to oxidative stress and DNA double-strand break in Saccharomyces cerevisiae. Free Radic. Biol. Med. 101:424-433.
  26. Klionsky, D. J. et al. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12(1):1-222.
  27. Yi, D.-G., and Huh, W.-K. (2015) UDP-glucose pyrophosphorylase Ugp1 is involved in oxidative stress response and long-term survival during stationary phase in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 467(4):657-663.
  28. Yi, D.-G., and Huh, W.-K. (2015) PKA, PHO and stress response pathways regulate the expression of UDP-glucose pyrophosphorylase through Msn2/4 in budding yeast. FEBS Lett. 589(18):2409-2416.
  29. Miller, K. E., Kim, Y., Huh, W.-K., and Park, H.-O. (2015) Bimolecular fluorescence complementation (BiFC) analysis: advances and recent applications for genome-wide interaction studies. J. Mol. Biol. 427(11):2039-2055.
  30. Lee, K., Sung, M.-K., Kim, J., Kim, K., Paik, H., Kim, B., Huh, W.-K., and Ideker, T. (2014) Proteome-wide remodeling of protein location and function by stress. Proc. Natl. Acad. Sci. U.S.A. 111(30):E3157-E3166.
  31. Ha, C. W., Kim, K., Chang, Y. J., Kim, B., and Huh, W.-K. (2014) The β-1,3-glucanosyltransferase Gas1 regulates Sir2-mediated rDNA stability in Saccharomyces cerevisiae. Nucleic Acids Res. 42(13):8486-8499.
  32. Song, Y. B., Park, C. O, Jeong, J.-Y., and Huh, W.-K. (2014) Monitoring G protein-coupled receptor activation using an adenovirus-based beta-arrestin bimolecular fluorescence complementation assay. Anal. Biochem. 449:32-41.
  33. Sung, M.-K., Lim, G., Yi, D.-G., Chang, Y. J., Yang, E. B., Lee, K., and Huh, W.-K. (2013) Genome-wide bimolecular fluorescence complementation analysis of SUMO interactome in yeast. Genome Res. 23(4):736-746.
  34. Choi, E.-W., Seen, D.-S., Song, Y. B., Son, H.-S., Jung, N.-C., Huh, W.-K., Hahn, J.-S., Kim, K., Jeong, J.-Y., and Lee, T. G. (2012) AdHTS: A high-throughput system for generating recombinant adenoviruses. J. Biotechnol. 162(2-3):246-252.
  35. Ha, C. W., Sung, M.-K., and Huh, W.-K. (2012) Nsi1 plays a significant role in the silencing of ribosomal DNA in Saccharomyces cerevisiae. Nucleic Acids Res. 40(11):4892-4903.
  36. Klionsky, D. J. et al. (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8(4):445-544.
  37. Pu, J., Ha, C. W., Zhang, S., Jung, J. P., Huh, W.-K., and Liu, P. (2011) Interactomic study on interaction between lipid droplets and mitochondria. Protein Cell 2(6):487-496.
  38. Shin, C.-S., and Huh, W.-K. (2011) Bidirectional regulation between TORC1 and autophagy in Saccharomyces cerevisiae. Autophagy 7(8):854-862.
  39. Ha, C. W., and Huh, W.-K. (2011) The implication of Sir2 in replicative aging and senescence in Saccharomyces cerevisiae. Aging 3(3):319-324.
  40. Kim, Y., Chay, K.-O., Song, Y. B., Kim, T.-Y., Kim, I., Han, S.-J., Ahn, Y., Cho, S.-H., Hoe, K.-L., Ahn, B. W., Huh, W.-K., and Lee, S.-R. (2011) Redox regulation of the tumor suppressor PTEN by glutaredoxin 5 and Ycp4. Biochem. Biophys. Res. Commun. 407(1):175-180.
  41. Lee, P., Paik, S. M., Shin, C. S., Huh, W.-K., and Hahn, J. S. (2011) Regulation of yeast Yak1 kinase by PKA and autophosphorylation-dependent 14-3-3 binding. Mol. Microbiol. 79(3):633-646.
  42. Ha, C. W., and Huh, W.-K. (2011) Rapamycin increases rDNA stability by enhancing association of Sir2 with rDNA in Saccharomyces cerevisiae. Nucleic Acids Res. 39(4):1336-1350.
  43. Chang, Y. J., Shin, C.-S., Han, D., Kim, J., Kim, K., Kwon, Y.-M., and Huh, W.-K. (2010) Genomewide profiling of rapamycin sensitivity in Saccharomyces cerevisiae on synthetic medium. Genomics & Informatics 8(4):177-184.
  44. Bandyopadhyay, S., Mehta, M., Kuo, D., Sung, M.-K., Chuang, R., Jaehnig, E. J., Bodenmiller, B., Licon, K., Copeland, W., Shales, M., Fiedler, D., Dutkowski, J., Guénolé, A., van Attikum, H., Shokat, K. M., Kolodner, R. D., Huh, W.-K., Aebersold, R., Keogh, M.-C., Krogan, N. J., and Ideker, T. (2010) Rewiring of genetic networks in response to DNA damage. Science 330(6009):1385-1389.
  45. Sung, M.-K., and Huh, W.-K. (2010) In vivo quantification of protein-protein interactions in Saccharomyces cerevisiae using bimolecular fluorescence complementation assay. J. Microbiol. Methods 83(2): 194–201.
  46. Kim, Y., Song, Y. B., Kim, T.-Y., Kim, I., Han, S.-J., Ahn, Y., Cho, S.-H., Chay, K.-O., Yang, S. Y., Ahn, B. W., Huh, W.-K., and Lee, S.-R. (2010) Redox regulation of the tumor suppressor PTEN by glutathione. FEBS Lett. 584(16):3550-3556.
  47. Song, Y. B., Jhun, M. A., Park, T., and Huh, W.-K. (2010) Quantitative proteomic analysis of ribosomal protein L35b mutant of Saccharomyces cerevisiae. Biochim. Biophys. Acta 1804:676-683.
  48. Shin, C.-S., Chang, Y.-J., Lee, H.-G., and Huh, W.-K. (2009) Rapamycin-Induced Abundance Changes in the Proteome of Budding Yeast. Genomics & Informatics 7:203-207.
  49. Shin, C.-S., Kim, S. Y., and Huh, W.-K. (2009) TORC1 Controls Degradation of Transcription Factor Stp1, a Key Effector of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae. J. Cell Sci. 122:2089-2099.
  50. Kim, T.-Y., Ha, C. W., and Huh, W.-K. (2009) Differential Subcellular Localization of Ribosomal Protein L7 Paralogs in Saccharomyces cerevisiae. Mol. Cells 27:539-546.
  51. Lee, K. Y., Chuang, H.-Y., Beyer, A., Sung, M.-K., Huh, W.-K., Lee, B., and Ideker, T. (2008) Protein networks markedly improve prediction of subcellular localization in multiple eukaryotic species. Nucleic Acids Res. 36:e136.
  52. Sung, M.-K., Ha, C. W., and Huh, W.-K. (2008) A vector system for efficient and economical switching of C-terminal epitope tags in Saccharomyces cerevisiae. Yeast 25:301-311.
  53. Huh, W.-K., Song, Y. B., Lee, Y.-S., Ha, C. W., Kim, S.-T., and Kang, S.-O. (2008) D-Erythroascorbic acid activates cyanide-resistant respiration in Candida albicans. Biochem. Biophys. Res. Commun. 369:401-406.
  54. Lee, H.-G., Lee, H.-S., Jeon, S.-H., Chung, T.-H., Lim, Y.-S., and Huh, W.-K. (2008) High-resolution analysis of condition-specific regulatory modules in Saccharomyces cerevisiae. Genome Biol. 9:R2.
  55. Sung, M.-K., and Huh, W.-K. (2007) Bimolecular fluorescence complementation analysis system for in vivo detection of protein-protein interaction in Saccharomyces cerevisiae. Yeast 24:767-775.
  56. Lee, M.-W., Kim, B.-J., Choi, H.-K., Ryu, M.-J., Kim, S.-B., Kang, K.-M., Cho, E.-J., Youn, H.-D., Huh, W.-K., and Kim, S.-T. (2007) Global protein expression profiling of budding yeast in response to DNA damage. Yeast 24:145-154.
  57. Howson, R., Huh, W.-K., Ghaemmaghami, S., Falvo, J. V., Bower, K., Belle, A., Dephoure, N., Wykoff, D. D., Weissman, J. S., and O’Shea, E. K. (2005) Construction, verification and experimental use of two epitope-tagged collections of budding yeast strains. Comp. Funct. Genom. 6:2-16.
  58. Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R., Belle, A., Dephoure, N., O'Shea, E. K., and Weissman, J. S. (2003) Global analysis of protein expression in yeast. Nature 425:737-741.
  59. Huh, W.-K., Falvo, J., Gerke, L., Carroll, A., Howson, R., Weissman, J. S., and O'Shea, E. K. (2003) Global analysis of protein localization in budding yeast. Nature 425:686-691.
08826 서울시 관악구 관악로1 서울대학교 자연과학대학 생명과학부 분자세포단백체학 연구실
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