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Park Seong-hoe

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Seong Hoe Park
Born1947 (age 76–77)
NationalitySouth Korean
Alma materSeoul National University College of Medicine
Known forT cell-T cell interaction,

Development of leukemic antigen,

Antigen-specific T cell tolerance
AwardsPfizer Medical Research Award (1976)
Emil von Behring Medical Award (1999)
National Academy of Science Award (2001)
Scientific career
FieldsImmunology, Pathology
InstitutionsProfessor, Seoul National University College of Medicine
Park Seong-hoe
Hangul
박성회
Revised RomanizationBak Seong-hoe
McCune–ReischauerPak Sŏnghoe

Seong Hoe Park (born October 3, 1947) is a South Korean immunologist and pathologist and a distinguished professor of pathology at the Seoul National University College of Medicine. He served as the chair of the Department of Pathology (2000–2004), the chair of the Graduate Program of Immunology (2002–2006), the president of Center for Animal Resource Development (2004–2006) at Seoul National University. He was the president of the Korean Association of Immunologists (2000–2001). Throughout his career as a T cell immunologist, Park established the theory of T cell-T cell interaction in human thymus, in which T cells expressing MHC class II drive previously unrecognized types of T cells and provide another significant developmental mechanism of T cells.

Another important achievement of his research is the induction of antigen-specific T cell tolerance, which has been a distant dream of immunologists for pinpoint-targeted control of the immune system. He successfully inhibited porcine pancreatic islet graft rejection in primates by preconditioning the host for the development of tolerogenic dendritic cells before the xenotransplantation (J Exp Med. 208:2477-2488, 2011). In this experiment, Park suggested a theoretical base of the prevention of graft rejection and the treatment of autoimmune diseases without serious complication. He also found the novel antigen JL1 on thymocytes, which has been developed as a therapeutic target for leukemia.

Today he is the director of the Transplantation Research Institute at the Seoul National University College of Medicine, and his team is conducting the basic research on the induction of T cell tolerance and the application of it to various immune diseases.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]

Education

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Seong Hoe Park was born in 1947 and spent his childhood in Incheon. He moved to Seoul and attended Seoul High School until the age of 18. He graduated from the Seoul National University College of Medicine in 1975 and received his PhD in Pathology from the same college in 1983. After his doctorate, he worked as a research fellow at the Harvard University Dana–Farber Cancer Institute.

Work

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As a professor of the department of pathology, he has investigated the developmental mechanism of T cells, particularly addressing the issues of human thymocytes distinct from mouse thymocytes. T cell has been believed to be developed only by thymocyte-thymic epithelial cell interaction in thymus, the “central dogma” in T cell development. However, he suggested the presence of another important developmental pathway of human T cells, denying the central dogma of developmental dependence of T cells on thymic epithelial cells. In 1992, Park found human fetal thymocytes expressed the class II major histocompatibility complex (MHC) molecules in contrast to mouse thymocytes (Hum Immunol. 33:294-298, 1992), and provided the first in vitro evidence that human thymocytes can interact with other thymocytes, possibly for T cell receptor recognition of T cell-derived peptides within MHC class II on neighboring thymocytes (Hum Immunol. 54:15-20, 1997). Since then, he has tried to demonstrate that thymocyte-thymocyte (or, T cell-T cell, so called T-T) interaction is really present and T cells can be developed by the interaction in vivo.

After almost 15 years, he finally established a delicately engineered mouse system in which T cells including thymocytes could expressed MHC class II molecules mimicking human T cells and successfully demonstrated that the T-T interaction occurred in the engineered murine thymus, resulting in the generation of functional CD4+ helper T cells (Immunity. 23:387-96, 2005). This work was supported by the data of another American research team (Immunity. 23:375-86, 2005), and contributed to the new line of research for the development of T cells of innate-like features (J Exp Med. 207:237-246, 2010). Based on this theory, he subsequently established humanized mouse system in which human T cells can develop via T cell-T cell interaction in the mouse.

During the same period, he was investigating the immune-modulating mechanism of dendritic cells. He screened the functional antigenic epitopes on dendritic cells, and found a novel epitope of ICAM-1. Through the development of an anti-ICAM1 antibody against the newly found epitope, he succeeded in inducing antigen-specific T cell tolerance via the development of tolerogenic semi-mature dendritic cells (J Exp Med. 208:2477-2488, 2011).

Applying this technology to the organ transplantation, his team extracted pancreatic islets from wild type pigs, and transplanted those into hepatic portal vein in non-human primates. His team treated the monkeys with the anti-ICAM1 epitope antibody before the xenotransplantation process, expecting the induction of immune-tolerance to the pancreatic antigens of other species in the non-human primates. This trial of xenotransplantation of pancreatic islets was proved to be a fantastic success, inhibiting graft rejection for almost a year. Park's work has been continued to the further researches on the possibilities of various clinical applications. To offer an extended therapeutic scope using the induction mechanism of immune tolerance, his team is investigating the possibilities of transplantation of various organs and treatment of autoimmune disease.

He also found the novel antigen JL1 expressed in thymocytes (J Exp Med. 178:1447-51, 1993). JL1 is a unique epitope of CD43 that is expressed only in immature leukocytes and leukemic cells, and a useful marker of acute leukemia. Based on this, follow-up experiments demonstrated that anti-JL1 antibody were able to effective eradicate leukemic cells.

As the director of Transplantation Research Institute and a distinguished professor of pathology at the Seoul National University College of Medicine, Park continues his study of T cell development, induction of immune tolerance, and their applications.

Awards

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  • Park won the Pfizer Medical Research Award 1976 and was awarded the Emil von Behring Medical Award 1999.
  • In 2001, Park was awarded the National Academy of Science Award for providing.

References

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  1. ^ Park SH, Bae YM, Kim TJ, Ha IS, Kim S, Chi JG, Lee SK. HLA-DR expression in human fetal thymocytes. Hum Immunol. 33:294-298, 1992
  2. ^ Park SH, Bae YM, Kwon HJ, Kim TJ, Kim J, Lee SJ, Lee SK. JL1, a novel differentiation antigen of human cortical thymocyte. J Exp Med. 178:1447-51, 1993
  3. ^ Choi EY, Park WS, Jung KC, Chung DH, Bae YM, Kim TJ, Song HG, Kim SH, Ham DI, Hahn JH, Kim J, Kim K, Hwang TS, ParkSH. Thymocytes positively select thymocytes in human system. Hum Immunol. 54:15-20,1997
  4. ^ Choi EY, Park WS, Jung KC, Kim SH, Kim YY, Lee WJ, ParkSH. Engagement of CD99 induces up-regulation of TCR and MHC class I and II molecules on the surface of human thymocytes. J Immunol, 161:749-754, 1998
  5. ^ Kim SH, Choi EY, Shin YK, Kim TJ, Chung DH, Chang SI, Kim NK, ParkSH. Generation of cells with Hodgkin's and Reed-Sternberg phenotype through downregulation of CD99 (Mic2). Blood, 92:4287-4295, 1998
  6. ^ Sohn HW, Choi EY, Kim SH, Lee I-S, Chung DH, Sung UA, Hwang DH, Cho SS, Jun BH, Jang JJ, Chi JG, ParkSH. Engagement of CD99 Induces Apoptosis Through a Calcineurin-Independent Pathway in Ewing's Sarcoma Cells. Am J Pathol, 153:1937-1945, 1998
  7. ^ Kim SH, Shin YK, Lee IS, Bae YB, Sohn HW, Suh YH, Ree HJ, Rowe M, ParkSH. Viral latent membrane protein 1(LMP-1)-induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype. Blood, 95:294-300, 2000
  8. ^ Shin YK, Choi EY, Kim SH, Chung J, Chung DH, Park WS, Jung KC, Kim HS, Park S, Kim HJ, Park MH, Min CK, Kim CC, ParkSH. Expression of Leukemia-Associated Antigen, JL1, in bone marrow and thymus. Am J Pathol, 158:1473-1480, 2001
  9. ^ Sohn HW, Shin YK, Lee I-S, Bae YM, Suh YH, Kim MK, Kim TJ, Jung KC, Park WS, Park C-S, Chung DH, Ahn K, Kim IS, Ko YH, Bang YJ, Kim CW and ParkSH. CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface. J Immunol, 166:787-794, 2001
  10. ^ Lee IS, Shin YK, Chung DH, ParkSH. LMP1-induced downregulation of CD99 molecules in Hodgkin and Reed-Sternberg cells. Leuk Lymphoma, 42:587-94, 2001
  11. ^ Lee I-S, Kim MK, Choi EY, Anja Mehl, Jung KC, Gil MC, Rowe M, ParkSH.CD99 expression is positively regulated by Sp1 and is negatively regulated by Epstein-Barr virus latent membrane protein 1 through nuclear factor-κB. Blood, 97:3596-3604, 2001
  12. ^ Park SH, Shin YK, Suh YH, Park WS, Ban YL, Choi H-S, Park HJ, Jung KC. Rapid divergency of rodent CD99 orthologs: implications for the evolution of the pseudoautosomal region. Gene, 353:177-88, 2005
  13. ^ Choi EY, Jung KC, Park HJ, Chung DH, Song JS, Yang SD, Simpson E, ParkSH. Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells. Immunity. 23:387-96, 2005
  14. ^ Lee YJ, Jung KC, ParkSH. MHC class II-dependent T-T interactions create a diverse, functional and immunoregulatory reaction circle. Immunol Cell Biol. 87:65-71, 2009
  15. ^ Lee YJ, J YK, Kang BH, Chung DH, Park C-G, Shin HY, Jung KC, ParkSH. Generation of PLZF+ CD4+ T cells via MHC class II–dependent thymocyte–thymocyte interaction is a physiological process in humans. J Exp Med. 207:237-246, 2010
  16. ^ Min HS, Lee YJ, Jeon YK, Kim EJ, Kang BH, Jung KC, Chang CH, ParkSH. MHC class II-restricted interaction between thymocytes plays an essential role in the production of innate CD8+ T cells. J Immunol. 186:5749-57, 2011
  17. ^ Jung KC, Park CG, Jeon YK, Park HJ, Ban YL, Min HS, Kim EJ, Kim JH, Kang BH, Park SP, Bae Y, Yoon IH, Kim YH, Lee JI, Kim JS, Shin JS, Yang J, Kim SJ, Rostlund E, Muller WA, ParkSH. In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates. J Exp Med. 208:2477-2488, 2011
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