연구자
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한재석, 이학박사
교수
Metabolic diseases, Endoplsamic resticulum stress, human diseases
순천향의생명연구원 본관동 409호
041-413-5027
hanjs015@sch.ac.kr
세포 소기관은 각기 고유의 기능을 가지고 있으며 이들 각 소기관의 항상성이 교란되었을 때 세포의 기능은 정상적으로 수행되지 못함. 조직을 이루는 세포들의 기능이 제대로 작동되지 못할 경우 인간의 질병이 나타남 (뇌세포 → 퇴행성뇌질환; 췌장베타세포 → 당뇨병; 간세포 → 간질환; 대식세포 → 염증반응 등). 본 연구실은 소포체 및 미토콘드리아의 스트레스 상황에서 이를 극복하기 위한 반응 (통합스트레스반응, Integrated Stress Response IRS)에 대한 분자기전 및 인간질병과 연관성을 탐구함.
Research Project
eIF2a 인산화에 의한 유전자 및 단백질 발현 조절
여러 질병의 병리기전에서 미토콘드리아 스트레스에 의한 미토콘드리아 내 단백질 조절
미토콘드리아 quality control (Mitophagy, Fusion and Fission)
미토콘드리아 Biogenesis 및 갈색지방 분화과정에서의 미토콘드리아 스트레스 역할 규명
미토콘드리아 스트레스에 의한 치매 (알츠하이머) 및 파킨슨병의 병리기전 연구
소포체 및 미토콘드리아 스트레스에 의한 대사염증성 간섬유화 및 인슐린 저항성 연구
소포체 및 미토콘드리아 스트레스에 의한 만능유도 줄기세포 분화 및 역분화 조절 기전
소포체 및 미토콘드리아 스트레스 반응 기전을 제어하는 물질 개발 및 기전 연구
Target Tissues and Human Diseases
Neurodegenerative diseases, Metabolic inflammation-related diseases (Diabetes and Liver diseases), Stem cells, Cancer, Drug development (Small molecules identification)
Research Techniques in the laboratory
Most of basic molecular biology techniques including qRT-PCR and Western blotting and cell culture.
Many cutting-edge techniques including Ribo-Seq, Polysome profiling, ChIP-Seq, Clip-Seq, Mass spectrometry (Proteomics), Bioinformatics, Animal models, HPLC, FACS, Virus work (Adeno and Lenti virus)
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Principal Investigator
Jaeseok Han, Ph.D. Education PhD: University of Calgary (2000-2005) M.S. Seoul National University (1997-1999) B.S. Seoul National University (1990-1997) Working Experience Associate Professor, SIMS, Soonchunhyang University (2018-present) Assistant Professor, SIMS, Soonchunhyang University (2014-2017) Staff Scientist, Sanford-Burnham Medical Research Institute (2012-2013) Postdoctoral Fellow, University of Michigan (2007-2011) Postdoctoral Fellow, Chicago Medical School (2005-2007) Postdoctoral Fellows
이지민 (Jimin Lee, Ph.D/Postdoctoral fellow) 박사 - 전남대학교 생물과학생명기술학과 - 소포체스트레스(ER stress) 억제를 통한 Beige adipocyte 분화 증가 - 소포체스트레스 조절을 통한 유도 만능 줄기 세포(iPSC) 효율 증가 - 소포체스트레스 조절을 통한 쿠퍼세포(Kupffer cell) 분극조절과 간 염증 및 섬유화 완화. Graduate Students
박소영 (Soyoung Park, Ms-Ph.D program) 학사 - 순천향대학교 생명공학과 & 의료생명공학과 - eIF2a 인산화에 의한 대식세포 (Macrophage)의 분극화 (Polarization) 연구 - eIF2a 인산화가 간섬유화 및 인슐린 저항성에 미치는 영향 연구 - 미토콘드리아 스트레스에 의한 미토콘드리아의 역동성 (Mitophagy, Fusion and Fission) 분자기전 연구 - PKR 및 eIF2a 인산화가 알츠하이머 (치매)에 미치는 영향 연구
Rosalie Elvira (Ms-Ph.D program) 학사 - 앗마자야 카톨릭 대학교 생명공학과, 인도네시아 자카르타 - 소포체 및 미토콘드리아 스트레스가 파킨슨병에 미치는 영향 연구 - 미토콘드리아 스트레스 반응 분자기전 연구 - 파킨슨병 환자 유래 인간 줄기세포에서 유래한 도파민 신경세포의 병리기전 연구
Fedho Kusuma 학사 - 아트마자야 카톨릭 대학교 생명공학과, 인도네시아 자카르타 - 미토콘드리아 스트레스가 근육세포 인슐린 저항성에 미치는 영향 - 미토콘드리아 스트레스에 의한 미토콘드리아 단백질 합성의 조절 기전 - 미토콘드리아 및 소포체 스트레스에 의한 One carbon metabolism 조절 기전 연구 - 미토콘드리아 스트레스에 의한 갈색지방 분화 및 에너지대사 조절 기전 Research Scientists
박상수 (Sangsoo Park, Research scientist) 석사- 울산대학교 의과대학 - 미토콘드리아 및 소포체 스트레스에 의한 암 발생 기전에서 mdm2 및 P53 단백질의 역할 규명 - 소포체 스트레스를 응용한 암 온열치료 효과 연구 |
1. Yong J, Johnson J, *Han J, *Kaufman RJ. (2020) Therapeutic opportunities around pancreatic β-cell ER stress in diabetes. Nat. Rev. Endocrinol. In press. * Co-corresponding author
2. Kim HK, Bhattarai KR, Junjappa RP, Ahn JH, Pagire SH, Yoo HJ, Han J, Lee D, Kim KW, Kim HR, Chae HJ. (2020) TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation. Nat. Commun. 11(1): 4012
3. Seo J, Lee CR, Paeng JC, Kwon HW, Lee D, Kim SC, Han J, Ku JL, Chae JH, Lim BC, Choi M. (2020) Biallelic mutations in ABCB1 display recurrent reversible encephalopathy Ann. Clin. Transl. Neurol. doi: 10.1002/acn3.51125. Online ahead of print
4. Kwon JH, Kim HK, Ha TW, Im JS, Song BH, Hong KS, Oh JS, *Han J, *Lee MR (2020) Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies Biomedicines 8(6): 176 * co-corresponding author
5. Ko MS, Yun JY, Baek IJ, Jang JE, Hwang JJ, Lee SE, Heo SH, Bader DA, Lee CH, Han J, Moon JS, Lee JM, Hong EG, Lee IK, Kim SW, Park JY, Hartig SM, Kang UJ, Moore DD, Koh EH, Lee KU. (2020) Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice. Autophagy
6. Ha TW, Jeong JH, Shin HS, Kim HK, Im JS, Song BH, Hanna J, Oh JS, *Woo DH, *Han J, *Lee MR (2020) Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress Cells 9(5): 1078 * co-corresponding author
7. Hiramatsu N, Chiang K, Aivati C, Rodvold JJ, Lee JM, Han J, Chea L, Zanetti M, Koo EH, Lin JH (2020) PERK-mediated induction of microRNA-483 disrupts cellular ATP homeostasis during the unfolded protein response J. Biol. Chem. 295(1):237-249
8. Park YJ, Choi DW, Cho SW, Han J, Yang S, Choi CY (2020) Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin Int. J. Mol. Sci. 21(15), 5360
9. Kim JS, Hwang SI, Ryu JL, Hong HS, Lee J-M, Lee SM, Jin X, Han C, Kim J-H, Han J*, Lee M-R*, Woo D-H* (2020) ER stress reliever enhances functionalities of in vitro cultured hepatocytes Stem Cell Res. 43:101732 * co-corresponding author
10. Elvira R, Cha SJ, Noh G-M, Kim K, Han J (2020) PERK-mediated eIF2a phosphorylation contritubes to the protection of dopaminergic neurons from chronic heat stress in Drosophila. Int. J. Mol. Sci. 21(3):845
11. Lee D, Hokinson D, Park S, Elvira R, Kusuma F, Lee J-M, Yun M, Lee S-G, Han J. (2019) ER stress induces cell cycle arrest at the G2/M phase through eIF2a phosphorylation and GADD45a. Int. J. Mol. Sci. 20(24):6039
12. Park S, Lim Y, Lee D, Elvira R, Lee JM, Lee MR, Han J. (2018) Modulation of protein synthesis by eIF2a phosphorylation protects cell from heat stress-mediated apoptosis. Cells. 7(12).pii:E254
13. Ha TW, Kang HS, Kim TH, Kwon JH, Kim HK, Ryu A, Jeon H, Han J, Broxmeyer HE, Hwang Y, Lee YK, Lee MR. (2018) MiR-9 Controls Chemotactic Activity of Cord Blood CD34⁺ Cells by Repressing CXCR4 Expression. Int. J. Stem Cells 11(2):187-195
14. Chandrahas VK, Han J*, Kaufman RJ* (2018). Coordinating Organismal Metabolism During Protein Misfolding in the ER Through the Unfolded Protein Response. Curr. Top. Microbiol. Immunol. 414:103-130 * co-corresponding author
15. Han J*, Kaufman RJ* (2017) Physiological/pathological ramifications of tranion factors in the unfolded protein response. Gen. Dev. 31(14):1417 * co-corresponding author
16. Choi WG*, Han J*, Kim JH, Kim MJ, Park JW, Song B, Cha HJ, Choi HS, Chung HT, Lee IK, Park TS, Hatzoglou M, Choi HS, Yoo HJ, Kaufman RJ, Back SH. (2017) eIF2α phosphorylation is required to prevent hepatocyte death and liver fibrosis in mice challenged with a high fructose diet. Nutrition Metabolism 14:48. * co-first author
17. Han J*, Kaufman RJ*. (2016) The role of ER stress in lipid metabolism and lipotoxicity. J. Lipid Res. 57(8):1329-1338 * co-corresponding author
18. Hassler JR, Scheuner DL, Wang S, Han J, Kodali VK, Li P, Nguyen J, George JS, Davis C, Wu SP, Bai Y, Sartor M, Cavalcoli J, Malhi H, Baudouin G, Zhang Y, Yates Iii JR, Itkin-Ansari P, Volkmann N, Kaufman RJ. (2015) The IRE1α/XBP1s Pathway Is Essential for the Glucose Response and Protection of β Cells. PLoS Biol. 13(10):e1002277.
19. Zhou AX, Wang X, Lin CS, Han J, Yong J, Nadolski MJ, Boren J, Kaufman RJ, Tabas I. (2015) C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions. Circ. Res. 116(11):1736-43
20. Han J, Song B, Kim J, Kodali VK, Pottekat A, Wang M, Hassler J, Wang S, Pennathur S, Back SH, Katze MG, Kaufman RJ. (2015) Antioxidants complement the requirement for protein chaperone function to maintain beta cell function and glucose homeostasis. Diabetes 64(8):2892-2904
21. Wang S, Park S, Kodali VK, Han J, Yip T, Chen Z, Davidson NO, Kaufman RJ. (2015) Identification of protein disulfide isomerase 1 as a key isomerase for disulfide bond formation in apolipoprotein B100. Mol. Biol. Cell 26(4):594-604
22. Scortegagna M, Kim H, Li JL, Yao H, Brill LM, Han J, Lau E, Bowtell D, Haddad G, Kaufman RJ, Ronai ZA (2014) Fine tuning of the UPR by the ubiquitin ligases Siah1/2. PLoS Genet 10(5); e1004348
23. Hiramatsu N, Messah C, Han J, LaVail MM, Kaufman RJ, Lin JH (2014) Translational and posttranslational regulation of XIAP by eIF2alpha and ATF4 promotes ER stress-induced cell death during the unfolded protein response. Mol. Biol. Cell 25 (9):1411-1420
24. Han J, Kaufman RJ (2014). Measurement of the Unfolded Protein Response (UPR) to investigate its role in adipogenesis and obesity. Methods Enzymol. 538C:135-50
25. Malhi H, Kropp EM, Clavo VF, Kobrossi CR, Han J, Kaufman RJ (2013) C/EBP homologous protein-induced macrophage apoptosis protects mice from steatohepatitis. J Biol. Chem. 288(26):18624-42.
26. *Krokowski D, *Han J, Saikia M, Majumder M, Yuan CL, Guan BJ, Bevilacqua E, Bussolati O, Broer S, Arvan P, Tchorzewski M, Snider MD, Puchowicz M, Croniger CM, Kimball SR, Pan T, Koromilas AE, Kaufman RJ, and Hatzoglou M. (2013). A Self-Defeating Anabolic Program Leads to beta cell apoptosis in ER Stress-Induced Diabetes via Regulation of Amino Acid Flux. J Biol. Chem. 288(24):17202-13
27 *Han J, *Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, Yuan CL, Krokowski D, Wang S, Hatzoglou M, Kilberg MS, Sartor MA, and Kaufman RJ. (2013). ER-stress-induced tranional regulation increases protein synthesis leading to cell death. Nat. Cell Biol. 15(5):481-90.
28. Han J, Murthy R, Wood B, Song B, Wang S, Sun B, Malhi H, Kaufman RJ (2013) ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice Diabetologia 56(4): 911-924
29. Oh YS, Lee YJ, Kang Y, Han J, Lim OK, and Jun HS. (2013). Exendin-4 inhibits glucolipotoxic ER stress in pancreatic beta cells via regulation of SREBP1c and C/EBPbeta tranion factors. J. Endocrinology 216(3):343-52
30. Wang S, Chen Z, Lam V, Han J, Hassler J, Finck B, Davidson N, and Kaufman RJ (2012) IRE1 alpha-XBP1s Induces PDI Expression to Increase MTP Activity for Hepatic VLDL Assembly and Lipid Homeostasis Cell Metab. 16(4):473-86.
31. Han J, Kim EH, Choi W, Jun HS. (2012) Glucose responsive artificial promoter-mediated insulin gene transfer improves glucose control in obese diabetic mice. World J. Gastroenterology 18(44):6420-6
32. Sakaki K, Yoshina S, Shen X, Han J, DeSantis RS, Xiong M, Mitani S, and Kaufman RJ (2012) RNA surveillance is required for endoplasmic reticulum homeostasis Proc. Natl. Acad. Sci. USA 109(21):8079-84.
33. Back SH, Kang SW, Han J and Chung HT (2012) Endoplasmic reticulum stress in the β-cell pathogenesis of type 2 diabetes Exp. Diabetes Res. 2012:618396.
34. Han J, McLane B, Kim EH, Yoon JW, and Jun HS (2011) Remission of Diabetes by Insulin Gene Therapy Using a Hepatocyte-Specific and Glucose-Responsive Synthetic Promoter Mol. Therapy 19(3):470-8
35. Liu MJ, Han J, Lee YS, Park MS, Shin S, Jun HS. (2010) Amelioration of hyperglycemia by intestinal overexpression of glucagon-like peptide-1 in mice. J. Mol. Med. 88(4):351-8.
36. Kaufman RJ, Back SH, Song B, Han J, Hassler J (2010) The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in β-cells. Diabetes Obes. Metab. 12 Suppl 2:99-107.
37. Back SH, Scheuner D, Han J et al. (2009). Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells. Cell Metab. 10(1): 13-26
38. *Han J, *Lee HW, Kwon H, Shin S, Yoon JW, Jun HS (2007) Engineered enteroendocrine Cells Secrete Insulin in Response to Glucose and Reverse Hyperglycemia in Diabetic Mice. Mol. Therapy 15(6):1195-202.
39. Lee YS, Hahm E, Liu M, Han J, Yoon JW, Jun HS (2006) Glucagon-Like Peptide-1 Gene Therapy in Obese Diabetic Mice Results in Long-Term Cure of Diabetes by Improving Insulin Sensitivity and Reducing Hepatic Gluconeogenesis. Diabetes 56(6):1671-9
40. Okitsu T, Kobayashi N, Jun HS, Shin S, Kim SJ, Han J, Kwon H, Sakaguchi M,Totsugawa T, Kohara M, Westerman KA, Tanaka N, Leboulch P, Yoon JW (2004) Transplantation of reversibly immortalized insulin secreting human hepatocytes controls diabetes in pancreatectomized pigs. Diabetes 3(1):105-12
41. Hirasawa K, Kim A, Han HS, Han J, Jun HS and Yoon JW (2002) Effect of p38 Mitogen-Activated Protein Kinase on the Replication of Encephalomyocarditis Virus. J. Virology 77(10):5649-56.
42. Sobel DO, Han J, Williams J, Yoon JW, Jun HS, Ahvazi B (2002) Gamma Interferon Paradoxically Inhibits the Development of Diabetes in the NOD Mouse. J. Autoimmunity 19(3):129-37
43. Jun HS, Chung YH, Han J, Kim A, Yoo S, Sherwin RS, Yoon JW (2002). Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase. Diabetologia 45(5):668-76
44. Han J, Yoo HY, Choi BH, Rho HM. (2000) Selective tranional regulations in the human liver cell by hepatitis B viral X protein. Biochem. Biophys. Res. Commun. 272(2); 525-530
45. Lee DH, Han J, Lee WG, Lee SW, Rho HM. (1998) Quadruplex amplification of polymorphic STR loci in a Korean population. Int. J. Legal Med. 111(6); 320-322
46. Han J, Lee DH, Rho HM (1998) Characteristics of hypervariable regions of mitochondrial DNA in korean population. J Biochem. Mol. Biol. 31(6):604-606
