BioWave,  Vol. 22 No. 1
건국대학교 발생유전학 연구실 조경상 교수
연구실 홈페이지
실험실 소개  
 
인간을 비롯한 지구상의 모든 생명체들은 특별한 유전암호체계(genetic code)를 가지며 이들의 조합과 발현으로 특성이 부여된다. 즉, 생명체는 유전자들에 의해 프로그램되어 있는 것이다. 또한 생명체는 주어진 환경에 따라 이 유전적 프로그램을 바꾸어 환경에 적응한다. 더 나아가 생명체가 노화할 때나 우리 몸에서 질병이 생겼을 때도 마찬가지로 세포 내의 유전적 프로그램은 바뀔 것이다. 우리 연구실은 이러한 유전적 프로그램을 밝혀(decoding) 생명현상의 원리를 규명하고, 더 나아가 재프로그램(reprogramming)을 통해 질병치료 등에 이용할 수 있는 유전적 기술을 개발하고자 한다.

특히 우리는 초파리(Drosophila)를 이용하여 난치병 원인 유전자의 기능과 이들 유전자가 관여하는 생체 내 기전을 밝힘으로써 난치병의 발병 원인을 규명하고자 한다. 초파리를 이용한 연구는 흔히 질병 연구에 사용되는 세포배양 실험이나 생쥐 모델에 비해 빠른 연구가 가능하다는 장점을 가진다. 또한 초파리는 유전학적 재료로서 그 시스템이 잘 구축되어 있어서 유전학적 스크리닝 등을 통해서 서로 상호 작용하는 인자들을 생체 내(in vivo)에서 찾기 쉽다. 이에 더하여, 초파리 게놈에는 약 74%의 인간질병 원인 유전자 유사체(homologue)가 포함되어 있다. 이러한 이유로 초파리는 난치병 발병의 분자 세포학적 기전을 연구하기에 가장 적합한 모델 중의 하나이며, 초파리를 이용한 연구 결과는 세포배양이나 생쥐 모델을 이용한 연구의 방향성을 제시해 준다.

우리 연구실의 주제는 크게 퇴행성 뇌질환과 노화 연관 유전자 발굴이다.

Lab_intro

 
연구분야  
 
Parkinsons Disease
One of the research goals of our laboratory is understanding the molecular mechanism by which Parkinson’s disease (PD) is caused. To achieve this goal, we use genetic approaches using Drosophila system which is the best developed genetic model.

PD is characterized by typical motor dysfunction and is thought to be caused by the loss of nigrostriatal dopaminergic (DA) neurons that connect the substantia nigra pars compacta (SNpc) to other brain regions. The death of these neurons has been closely linked to oxidative stress. Markers of oxidative damage to lipids, proteins and DNA, as well as mitochondrial DNA deletions, which can be caused by oxidative stress, are significantly elevated in postmortem samples of the SNpc of PD patients.

Parkinsons Disease_1

Among the genes related to PD, DJ-1 is the most closely associated with oxidative stress. Previous studies have demonstrated that DJ-1β loss-of-function mutants are acutely sensitive to oxidative stress and prone to locomotive dysfunction, resembling the phenotypes seen in PD.

Our lab identified a Drosophila homologue of death domain-associated protein (Daxx), Daxx-like protein (DLP), as a mediator of Drosophila DJ-1β mutant phenotypes (Hwang et al., 2013). Our results show that Drosophila DJ-1 protects dopaminergic neurons from oxidative stresses by regulating the subcellular localization and gene expression of DLP, providing a clue to understanding the molecular mechanism underlying oxidative stress-induced neuronal death in PD.

Parkinsons Disease_2

Alzheimers Disease
Alzheimer’s disease (AD) is a neurodegenerative disorder, with typical clinical symptoms including memory loss and changes in personality, and is characterized by extracellular senile plaques, neurofibrillary tangles, neuronal cell death and progressive neurodegeneration. The extracellular plaques predominantly contain amyloid-beta (Aβ) peptides, and important roles of Aβ as a risk factor in the pathogenesis of AD have been suggested.

Alzheimers Disease_1

Through the genetic screening to find AD-associated genetic factors, our laboratory identified several candidate genes which are implicated in the cytotoxicity of Aβ. Now we are characterizing their roles in AD pathogenesis.

Expression of the Down syndrome critical region 1 (DSCR1) protein, an inhibitor of the Ca2+-dependent phosphatase calcineurin, is elevated in the brains of individuals with Down syndrome (DS) or Alzheimer’s disease (AD). However, the roles of DSCR1 on the pathogenesis of AD remain controversial. From the genetic approaches in Drosophila, we found that DSCR1 overexpression exacerbates Aβ42 phenotypes in a Drosophila AD model, which suggests that DSCR1 upregulation or calcineurin downregulation in the brain might exacerbate Aβ42-associated neuropathogenesis in AD or DS.

Alzheimers Disease_2

Aging
Ageing of organisms is under genetic control, and key genes involved in the regulation of ageing and the mechanisms by which these genes control ageing have been identified.

One of the prominent markers of ageing is increased aggregation of a large number of ubiquitinated proteins in muscles of both Drosophila and mouse. However, the molecular mechanism underlying the ageing-associated increased aggregation of proteins is not fully understood.

Aging_1

We are studying the molecular mechanism through which protein aggregation is increased during ageing, and the role of the aggregation of ubiquitinated protein in ageing process.

Aging_2

 
연구성과  
 

Publications(대표 논문들)

  • Shin M, Liu QF, Choi B, Shin C, Lee B, Yuan C, Song YJ, Yun HS, Lee IS, Koo BS, Cho KS. (2019)
    Neuroprotective effects of limonene (+) against Aβ42-induced neurotoxicity in a Drosophila model of Alzheimer's disease.
    Biol Pharm Bull., doi: 10.1248/bpb.b19-00495

  • Cho KS, Lee JH, Cho J, Cha GH, Song GJ (2019)
    Autophagy Modulators and Neuroinflammation.
    Curr Med Chem., doi: 10.2174/0929867325666181031144605

  • Liu QF, Jeon Y, Sung YW, Lee JH, Jeong H, Kim YM, Yun HS, Chin YW, Jeon S, Cho KS*, Koo BS*. (2018)
    Nardostachys jatamansi DC ethanol extract ameliorates Aβ42 cytotoxicity.
    Biol Pharm Bull., doi: 10.1248/bpb.b17-00750

  • Cho KS, Shin M, Kim S, Lee SB (2018)
    Recent Advances in Studies on the Therapeutic Potential of Dietary Carotenoids in Neurodegenerative Diseases.
    Oxidative Medicine and Cellular Longevity, 2018:4120458

  • Lee J, Hwang YJ, Kim Y, Lee MY, Hyeon SJ, Lee S, Kim DH, Jang SJ, Im H, Min S-J, Choo H, Par AN, Kim DJ, Cho KS, Kowall NW, Ryu H (2018)
    Remodeling of heterochromatin structure slows neuropathological progression and prolongs survival in an animal model of Huntington’s disease.
    Acta Neuropathol., 134(5):729-748

  • Lee JH, Kim J-H, Kim S, Cho KS*, Lee SB* (2018)
    Chromatin Changes Associated with Neuronal Maintenance and Their Pharmacological Application.
    Current Neuropharmacology, 16:118-125

  • Kim J-H, Lee JH, Lee, I_S, Lee SB, Cho KS (2017)
    Histone Lysine Methylation and Neurodevelopmental Disorders.
    Int. J. Mol. Sci., 18:1404

  • Lee S, Bang SM, Hong YK, Lee JH, Jeong H, Park SH, Liu QF, Lee IS, Cho KS. (2016)
    The calcineurin inhibitor Sarah (Nebula) exacerbates Aβ42 phenotypes in a Drosophila model of Alzheimer's disease.
    Dis. Model. Mech., 9(3):295-306

  • Morimoto M, Choi K, Boerkoel CF, Cho KS. (2016)
    Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia.
    Nucleus, 7(6):560-571

  • Liu QF, Jeong H, Jang Ho Lee, Hong YK, Oh Y, Kim YM, Suh YS, Bang S, Yun HS, Lee K, Cho SM, Lee SB, Jeon S, Chin YW, Koo BS, Cho KS. (2016)
    Coriandrum sativum suppresses Aβ42-induced ROS increases, glial cell proliferation, and ERK activation.
    The American Journal of Chinese Medicine, 44(7):1-23

  • Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS. (2013)
    Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO.
    PLoS Genet., 9(4):e1003412

  • Han SY, Lee M, Hong YK, Hwang S, Choi G, Suh YS, Park SH, Lee S, Lee SH, Chung J, Baek SH, Cho KS. (2012)
    Tsp66E, the Drosophila KAI1 homologue, and Tsp74F function to regulate ovarian follicle cell and wing development by stabilizing integrin localization.
    FEBS Lett., 586(22):4031-4037

  • Lee J, Hong YK, Jeon GS, Hwang YJ, Kim KY, Seong KH, Jung MK, Picketts DJ, Kowall NW, Cho KS, Ryu H. (2012)
    ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease.
    Cell Death Differ., 19(7):1109-1116

  • Cha, G. H., Kim S., Park, J., Lee, E., Kim, M., Lee, S. B., Kim, J., M., Chung, J., Cho, K. S. (2005)
    Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila.
    Proc. Natl. Acad. Sci. USA, 102:10345-10350
 
     
 
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  지도교수: 조경상

 연구교수: 원소윤 박사
 Post-doc: 이장호 박사
 M.S. / Ph.D. student : 신명철
 M.S. student : 최병윤, 원춘옥, 이반석, 신창민, 박영재, 장석희
Contact : 02-450-3424 (Tel.) /
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등록일 2019.12.27
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