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21세기 첨단과학의 꽃 Life Science
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02-6490-2660~1
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home > 학과소개 > Labs
Cellular Signal Transduction Lab
Professor : Eek-hoon Jho
Tel : +82-2-6490-5625
Location : Natural Science Building Room 8-503
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  • Introduction

    Our lab is mainly focusing on identification of mechanisms for the signal transduction of Wnt signaling. The Wnt signaling plays pivotal roles in the regulation of cell proliferation and differentiation during embryonic development of multicellular organisms and in the maintenance of homeostasis in adult tissues. Therefore misregulation of Wnt signaling leads to diverse human diseases such as cancers and Alzheimer’s disease etc. Recently, the list of diseases that are due to the misregulation of Wnt signaling has been increased and more researchers are interested in curing diseases by controlling Wnt signaling. We are trying to identify novel regulation mechanisms for Wnt signaling with aim to provide therapeutic targets for human diseases. The detail information about Wnt signaling can be obtained at the Wnt homepage (http://www.stanford.edu/~rnusse/wntwindow.htm).


  • Current Projects

    1. Identification of novel regulators of Wnt signaling.

    Fig.1 shows some of proteins are known to be involved in the regulation of Wnt signaling. However, the list of proteins which control Wnt signaling is expanding. In our lab we are trying to find novel regulators of Wnt signaling. Currently, we have identified DP1, Peg1/MEST, Ptpro and Arf1 as novel regulators for Wnt signaling. We are using biochemical and cell biological approaches to prove their involvement in the regulation of Wnt signaling. In addition, we are using Xenopus embryo and Drosophila system in collaboration with Dr. Jin-Kwan Han at POSTEC and Dr. Vladimir Katanaev at University of Konstanz (Germany), respectively.

    2. Regulation of differentiation of embryonic stem cell via changing the level of Tcf/Lef1.

    The role of Wnt signaling in the regulation of stemness and differentiation of embryonic stem cell is still controversial. Recently we found that Tcf/Lef1, terminal regulators of Wnt/b-catenin signaling, plays critical role in the maintenance of stemness and differentiation of mouse embryonic stem cell. In order to study the role of Wnt signaling we also established methods to derive embryonic stem cell from Wnt knock-out mice. Fig.2 shows results for the derivation of mouse embryonic stem cells from Wnt4 and Wnt5a knock-out mice.

    3. Study the role of Wnt signaling in neuro-degeneration and generation of mice models for the

    neuro-degeneration
    We have examined that the degeneration of hippocampal neurons can be caused by mis-regulation of Wnt/b-catenin signaling. Using primary hippocampal neuronal culture system and Tet-on inducible transgenic mice we could provide evidences for an idea that down-regulation of Wnt/b-catenin signaling causes degeneration of hippocampal neurons in vivoand may be a cause of neurodegenerative diseases related to an anxiety related response. Currently we are extending our findings to identify linkage between mis-regulation of Wnt signaling and Alzheimer’s disease in collaboration with physicians who are seeing patients suffering from Alzheimer’s disease. We plan to isolate novel biomarkers which can be used for the diagnosis of Alzheimer’s disease in early stage. Fig.3 shows results for the degeneration of hippocampal neurons when Wnt/b-catenin signaling is inhibited.

  • Current Lab membersand Research Projects

    PI : Eek-hoon Jho, Ph. D. (ej70@uos.ac.kr)

    Ph.D. Candidates
    - Hanjun Kim, MS (kimbab1jul@empal.com)
    : Degeneration of Hippocampal neuron/ Role of Wnt signal during the differentiation of ES cells.
    - Sewoon Kim, MS (ksw8007@naver.com)
    : E3 ligase for Axin/ Role of Tcf/Lef1 in the regulation of stemness of ES cells
    - Wantae Kim, MS (staymyblog@naver.com)
    : Novel role of DP1 in the regulation of Wnt signaling/Regulation of Hippo signaling by Wnt signaling.
    - Boksik Cha, MS (carboxy78@hotmail.com)
    : Role of protein Arginine methylation in the regulation of Wnt signaling.
    - Hwajin Jung, MS (bbabba1218@hanmail.net)
    : Role of Peg1/Mest in the regulation of Wnt signaling during adipogenesis.
    - Minseong Kim, MS (megryan20@naver.com)
    : Identification of a novel receptor for Wnt/ Regulation of Hippo signaling by Wnt signaling.

    M.S. Candidates
    - Taeyoon Kim, BA (mirib4gi@hanmail.net) : Role of Arf1 in the regulation of Wnt signaling.
    - Hyejoo Lee, BA (hjjm24@hanmail.net) : Role of Tcf/Lef1 during differentiation of ES cells.
    - Sung-Ho Moon, BA (moon20000@hanmail.net) : Regulation of Hippo signaling by Wnt signaling.
    - Minhye Kim, BA (asuka16@hanmail.net) : Role of Arf1 in the regulation of Wnt signaling.

    Undergraduate
    - Byulnim Hwang (oppa21c@hanmail.net)
    : Role of protein Arginine methylation in the regulation of Wnt signaling.

  • Recent Publications
    1. Kim W, Kim SY, Kim T, Kim M, Bae DJ, Choi HI, Kim IS and Jho EH. ADP-ribosylation factor regulates Wnt/b-
    catenin signaling via control of LRP6 phosphorylation. Oncogene. In press.

    2. Kim W, Kim H, Katanaev V, Lee S, Ishitani T, Cha B, Han JK and Jho EH.Dual functions of DP1 promote biphasic
    Wnt-on and Wnt-off states during anteroposterior neural patterning.EMBO J. In press.

    3. Cha B and Jho EH.Protein arginine methyltransferases (PRMT) as therapeutic targets.Expert Opinion on
    Therapeutic Targets16(7):651-64. (Invited review).

    4. Kim SY, Kim S, Yun-Choi HS and Jho EH.2011 Wnt5a potentiates U46619-induced platelet aggregation via the
    PI3K/Akt pathway. Mol Cells.32(4):333-6

    5. Lyu J, Jho EH, Lu, W. 2011Smek promotes histone deacetylation to suppress transcription of Wnt target gene
    brachyury in pluripotent embryonic stem cells. Cell Research 21(6):911-21

    6. Jung H, Lee SK and Jho EH. 2011 Mest/Peg1 inhibits Wnt signaling via regulation of LRP6 glycosylation.
    Biochemical Journal 436(2):263-9

    7. Kim SY, Kim S, Kim JM, Jho EH, Park S, Oh D and Yun-Choi HS. 2011 PKC inhibitors RO 31-8220 and Gø 6983
    enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. BMB Report44(2):140-5

    8. Cha B, Kim W, Kim YK, Hwang BN, Park SY, Yoon JW, Park WS, Cho JW, Bedford MT and Jho EH.
    2011Methylation by protein arginine methyltransferase1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene 30(20):2379-89

    9. Kim H, Won S, Hwang DY, Lee JS, Kim M, Kim R, Kim W, Cha B, Kim T, Kim D, Costantini F, Jho EH. 2011.
    Down-regulation of Wnt/ -catenin signaling causes degeneration of hippocampal neurons in vivo. Neuro.Aging.32(12):2316.e1-2316.e15

    10. Kim SW, Jho EH.2010. The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad
    Ubiquitination Regulatory Factor 2 (Smurf2).J. Biol. Chem.285(47):36420-6

    11. Kim M, Kim H, Jho EH. 2010. Identification of ptpro as a novel target gene of Wnt signaling and its potential
    role as a receptor for Wnt. FEBS Letters 584(18):3923-28

    12. Jung H, Kim H, Lee SK, Kim R,Kopachik W, Han JK, Jho EH. 2009. Negative feedback regulation of Wnt signaling
    by G -mediated reduction of Dishevelled. Exp. Mol. Med. 41(10):695-706.

    13. Kim JA, Kang YJ, Park G, Kim M, Park YO, Kim H, Leem SH, Chu IS, Lee JS, Jho EH, Oh IH. 2009. Identification
    of a Stroma-Mediated Wnt/β-catenin Signal Promoting Self-renewalof Hematopoietic Stem Cells in Stem Cell Niche. Stem Cells.27(6):1318-29.

    14. Kim H, Cheong SM, Ryu J, Jung HJ, Jho EH and Han JK. 2009. XenopusWntless and the Retromer complex
    cooperate to regulate XWnt4 secretion. Mol Cell Biol.29(8):2118-28.

    15. Kim SM, Choi E, Song, K, Kim S, Seo E, Jho EH, Kee SH. 2009.Axin localizes to mitotic spindles and
    centrosomes in mitotic cells. Exp Cell Res.315(6):943-54.

    16. Seo E, Kim S, Jho EH. 2009.Induction of cancer cell-specific death via MMP2 promoter-dependent expression
    of Bax. BMB reports.42(4):217-22.

    17. Seo E, Kim H, Kim R, Yun S, Kim M, Han JK, Costantini F, Jho EH. 2009. Multiple isoforms of beta-TrCP display
    differential activities in the regulation of Wnt signaling.Cell Signal. 21:43-51.

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