BioLab
BioWave,  Vol. 21 No. 2
UNIST 종양후생유전학 연구실 고명곤 교수
연구실 홈페이지
실험실 소개 
Deciphering and exploiting cancer-specific alterations to improve cancer therapy

How do alterations in epigenetic landscape disturb the barrier between normal and malignant states to cause cancers? How can we translate these cancer-related aberrations into more efficient cancer therapy? These are two overarching questions that our research is currently addressing. The intricate interplay between genetic and epigenetic pathways plays key roles in regulating normal and malignant cellular development.

1. 생체 내 암 발생 원리 규명
2. 세포의 정상 분화 및 암화의 조절 메커니즘 규명
3. 암특이적인 변이를 표적으로 하는 새로운 표적항암치료제 개발
4. 세포 내 대사의 후생유전학적 조절
연구분야 
Recent technological advances have enabled us to gain comprehensive views of genetic and epigenetic modifications in normal and malignant states. By taking a multidisciplinary approach, including mouse genetics, cellular and molecular biology, biochemistry and genomics, coupled with studies of hematopoietic and non-hematopoietic cancers, we aim to understand how dysregulation of key epigenetic players leads to the onset and progression of cancers, thereby identifying novel pathways that can be clinically targeted for the prevention and/or treatment of cancers.

Epigenetic alterations in cancer
The recent discovery of TET (Ten-eleven-translocation) enzyme functions has led to a paradigm shift in our understanding of how imbalances in DNA methylation-demethylation dynamics are coupled to cancers. The TET proteins (TET1, TET2 and TET3) alter DNA methylation status by sequentially oxidizing 5-methylcytosine. The resulting oxidized methylcytosines function as intermediates in DNA demethylation as well as independent epigenetic marks. Because DNA methylation and hydroxymethylation are highly aberrant in cancers, leading to abnormal gene expression and genomic instability, we will take the DNA methylation-demethylation cycles as a starting point of our research, with an emphasis on understanding the role of TET proteins in normal and oncogenic hematopoiesis.

- 혈액암(백혈병) 및 고형암 (간암, 대장암) 발달
- 정상 성체줄기세포 혹은 암줄기세포 조절 메커니즘
- 생체 내 대사, 염증 및 면역반응
- 유전자 발현 및 세포 분화의 후생유전학적 조절 기전

Epigenetic alterations in cancer

Translational application of cancer-specific epigenetic aberrations
Global epigenomic alterations common in cancers represent an attractive target for cancer therapy because epigenetic marks are generated and erased in a highly dynamic and reversible manner. Loss of TET function is generally associated with malignant transformation. Thus, we are exploring whether manipulation of methylcytosine oxidation status by targeting TET enzymes displays clinical efficacy in cancer patients. To this aim, we will identify proteins or small molecules that physically or functionally interact with TET enzymes, then molecular basis of their action and therapeutic effects will be rigorously tested alone or in combination with conventional therapy.

- 종양특이적 후생유전학적 변이를 표적으로 하는 신개념 항암 치료제 개발

Translational application of cancer-specific epigenetic aberrations

연구성과 
Selected Publications

  • Jungeun An, Anjana Rao, Myunggon Ko (2017)
    TET family dioxygenases and DNA demethylation in stem cells and cancers.
    Exp. Mol. Med., 49(4):e323


  • Nair VS, Song MH, Ko M, Oh KI (2016)
    DNA Demethylation of the Foxp3 Enhancer Is Maintained through Modulation of Ten-Eleven-Translocation and DNA Methyltransferases.
    Mol. Cells, 39(12):888-897


  • Xiaotian Zhang*, Jianzhong Su*, Mira Jeong*, Myunggon Ko, Yun Huang, Hyun Jung Park, Anna Guzman, Yong Lei, Yung-Hsin Huang, Anjana Rao, Wei Li & Margaret A Goodell (2016)
    DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells.
    Nat. Genet., 48(9):1014-23


  • Sara Motagner, Cristina Leoni, Stefan Emming, Giulia Della Chiara, Chiara Balestrieri, Iros Barozzi, Viviana Piccol, Susan Tougher, Myunggon Ko, Anjana Rao, Cioacchino Natoli, Silvia Monticelli (2016)
    TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities.
    Cell Reports, 15:1566-1579


  • Jungeun An, Edahi Gonzalez-Avalos, Ashu Chawla, Mira Jeong, Isaac F. Lopez-Moyado, Wei Li, Margaret A. Goodell, Lukas Chavez*, Myunggon Ko*, Anjana Rao* (2015)
    Acute loss of TET function results in aggressive myeloid cancer in mice.
    Nat. Comm., 6:10071 (*co-corresponding authors)


  • Myunggon Ko#, Jungeun An, Anjana Rao (2015)
    DNA methylation and hydroxymethylation in hematologic differentiation and transformation.
    Curr. Opin. Cell Biol., 37: 91-101 (#corresponding author)


  • Jae-A Han, Jungeun An, Myunggon Ko (2015)
    Functions of TET proteins in hematopoietic transformation.
    Mol. Cells, 38:925-935


  • Evisa Gjini, Marc R. Mansour, Jeffry D. Sander, Nadine Moritz, Ashley T. Nguyen, Michiel Kesarsing, Si Chen, Myunggon Ko, You-Yi Kuang, Song Yang, Yi Zhou, Leonard I. Zon, J. Keith Joung, Anjana Rao, A. Thomas Look (2015)
    A zebrafish model of myelodysplasia produced through tet2 genomic editing.
    Mol. Cell. Biol., 35:789-804


  • Myunggon Ko*, Jungeun An*, William A. Pastor, Sergei Koralov, Klaus Rajewsky, Anjana Rao (2015)
    TET proteins and 5-methylcytosine oxidation in hematological cancers.
    Immunological Reviews, 263:6-21 (*equally contributed)


  • Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Ko M, Wang H, Chen R, Gunaratne P, Godley LA, Darlington GJ, Rao A, Li W and Goodell MA (2014)
    Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a.
    Nat. Genet., 46:17-23


  • Myunggon Ko*, Jungeun An*, Hozefa S. Bandukwala, Lukas Chavez, Tarmo Aijo, William A. Pastor, Matthew F. Segal, Huiming Li, Kian Peng Koh, Harri Lahdesmaki, Patrick G. Hogan, L. Aravind, Anjana Rao (2013)
    Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.
    Nature, 497:122-126


  • Masato Sasaki, Christiane B. Knobbe, Momoe Itsumi, Andrew J. Elia, Isaac S. Harris, Iok In Christine Chio, Rob A. Cairns, Susan McCracken, Andrew Wakeham, Jillian Haight, Annick You Ten, Bryan Snow, Takeshi Ueda, Satoshi Inoue, Kazuo Yamamoto, Myunggon Ko, Anjana Rao, Katharine E. Yen, Shinsan M. Su, and Tak Wah Mak (2012)
    D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function.
    Genes Dev., 26:2038-2049


  • Jinwook Choi*, Myunggon Ko* Shin Jeon, Yoon Jeon, Kyungsoo Park, Changjin Lee, Ho Lee, and Rho H (2012)
    The SWI/SNF-like BAF complex is essential for early B cell development.
    J. Immunol., 188:3791-3803


  • Myunggon Koand Anjana Rao (2011)
    TET2: epigenetic safeguard for HSC.
    Blood, 118:4501-4503


  • Myunggon Ko*, Hozefa S. Bandukwala*, Jungeun An, Edward D. Lamperti, Elizabeth C. Thompson, Ryan Hastie, Angeliki Tsangaratou, Klaus Rajewsky, Sergei B. Koralov, and Anjana Rao (2011)
    Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice.
    Proc. Natl. Acad. Sci. USA, 108:14566-14571


  • William A. Pastor*, Utz J. Pape*, Yun Huang*, Hope R. Henderson, Ryan Lister, Myunggon Ko, Erin M. McLoughlin, Yevgeny Brudno, Sahasransu Mahapatra, Philipp Kapranov, Mamta Tahiliani, George Q. Daley, X. Shirley Liu, Joseph R. Ecker, Patrice M. Milos, Suneet Agarwal & Anjana Rao (2011)
    Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells.
    Nature, 473:394-397


  • Jeongeun Ahn*, Myunggon Ko*, Changjin Lee, Jieun Kim, Hana Yoon, and Rho H.Seong (2011)
    Srg3, a mouse homolog of BAF155, is a novel p53 target and acts as a tumor suppressor by modulatingp21WAF1/CIP1expression.
    Oncogene, 30:445-456


  • Myunggon Ko*, Yun Huang*, Anna M. Jankowska, Utz J. Pape, Mamta Tahiliani, Hozefa S. Bandukwala, Jungeun An, Edward D. Lamperti, Kian Peng Koh, Rebecca Ganetzky, X. Shirley Liu, L. Aravind, Suneet Agarwal, Jaroslaw P. Maciejewski& Anjana Rao (2010)
    Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2.
    Nature, 468:839-843
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     Combined M.S./Ph.D. candidate : 정형민,변성준
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