KOSEN 한인과학기술자네트워크

Our biological body depends on diverse organs, each of which in turn consists of different cells and depends on their functions. To play their functions properly and on time as need, the cells communicate with extracellular microenvironments including diverse soluble factors and neighboring cells. To achieve the efficient bidirectional communications between cells and microenvironments, the membrane receptors such as integrins, tetraspan(in)s, growth factor receptors (GFRs), GPCR, and cadherins dynamically play pivotal roles in mediating the both intracellular and extracellular spaces. Understanding their roles and mechanisms to function will allow clues to develop reagents to deal with diseases due to abnormal cellular functions. 1. Dynamics and Mechanisms of Cellular Functions (adhesion, morphology, migration, and invasion) in 2D or 3D Cells sense extracellular cues including extracellular matrix, cytokines, chemokines, growth factors and even neighboring cells. Via mediations by membrane receptors such as integrin, tetraspan(in), and GFR, intracellular signal pathways are activated leading to dynamic alterations in cellular morphology (via Rho GTPase activation and actin reorganization), proliferation, migration, and invasion. To understand mechanisms of the cell functions, in vitro cell and in vivo animal systems are examined to answer how the functions can be regulated (up- or down-regulated) and which signaling molecules are critically underlying for. Current topics include followings. (a)Dynamics and molecular basis of filopodia and lamellipodia formation (b)Dynamics of invadopodia by a tetraspan, TM4SF5 (c)Dynamics and mechanisms for TM4SF5-dependent cell adhesion and migration (d)Regulation of cell cycle via Rho GTPase (e)Cell adhesion-dependent protein modification (phosphorylation versus O-glycosylation) and actin reorganization 2. Communication between (tumor) cells and microenvironments Cell functions such as adhesion, spreading, proliferation, migration and invasion depend critically on extracellular matrix and soluble factors. To respond to extracellular cues, cell membrane receptors including integrin, TM4SF5 (a tetraspan collaborative with integrins), GFRs, and E-cadherins can transduce intracellular signaling pathways in direct (a receptor type alone) or indirect (collaboratively via multiple receptors types) manners. By virtues of the signal transductions, alterations in activity, expression, and localization of signaling molecules allow modulation of diverse cellular functions leading for (tumor) cells to gain more efficient functions within certain microenvironments. To understand the nature of the communication can allow us to develop anti-tumor reagents, which may be designed to suppress tumor cells’ functions. Followings are intensively investigated. (a) Angiogenesis via cross-talks between TM4SF5 and integrin alpha 5 on hepatocytes (b) Migration and invasion of hepatocarcinoma cells under collagen type I environments (c) TM4SF5-mediated FAK and c-Src regulation during cell migration (d) Mechanisms of TGF-beta1-mediated TM4SF5 induction and significance in liver pathology 3. Development of a small synthetic compound as an anti-TM4SF5 inhibitor: anti-tumor reagent? We observed that Korean patients with liver or colon carcinoma overexpressed TM4SF5, which is critically involved in loss of contact inhibition (i.e., multilayer growth), migration, invasion, and angiogenesis. With rationales that anti-TM4SF5 reagent(s) may functions as an anti-tumor reagent specifically against TM4SF5-dependent tumors, via a collaboration with Dr. KH Park group at Gyeongsang National University, we have identified a small synthetic compound that inhibits the TM4SF5-mediated effects, presumably by affecting the 2nd extracellular loop and/or N-glycosylation status of TM4SF5. We are currently trying to understand the nature of the candidate for preclinical studies.

본 연구실은 암세포주변 미세환경을 이루는 인자들과 암세포와의 상호 소통 (communication)을 통하여, 세포의 암적 기능들(adhesion, morphology, transdifferentiation, migration, invasion 등)이 조절되는 기전들을 분자적 수준에서 규명하고, 그들을 제어할 수 있는 단서를 찾고자 한다. 특히, 간상피세포를 포함하여, 암의 근원이 되는 상피세포들의 세포막에 발현하는 다양한 막단백질 혹은 세포막 receptor들의 상호 신호전달 활성 및 기능을 통하여, 세포의 형태, 전이, 이동, 및 침윤 등의 기능을 2차원 및 세포외기질로 둘러싸인 3차원적 환경에서 어떻게 조절되고 그 기전을 제어할 수 있는 지를 알고자 세포 및 동물, 그리고 임상조직을 이용하는 연구들을 수행하고 있다. 박사후연구원, 서울대 약대 및 유전공학(협동과정)의 박사과정, 석박사통합과정, 그리고 석사과정 연구원으로 구성되어 밤낮으로 연구에 매진하고 있는 본 연구실을 소개합니다.

본 연구실에서는 과학자로서의 꿈을 향한 과정에서, 생화학, 세포생물학, 및 분자생물학적 연구기법을 세포 (2차원 및 3차원적 배양환경), 동물, 환자조직 차원에서 적극적인 approaches를 통하여, 세포의 부착, 형태, 이동, 침윤등 다양한 기능의 제어 시스템을 기전적으로 이해하고 규명하는 시도를 추구함으로서, 체계적인 연구의 경험을 갖게끔 한다고 할 수 있다. 석사, 박사, 그리고 나아가 박사후과정에서의 훌륭한 연구자적 자신감과 고찰능력을 연구원들간, 지도교수와의 충분하게 논의하여 각 연구원들의 장래 개발에 낭비 시간이 생기지 않도록 하고 있다.

교수: 이정원 | 박사후연구원: 김태영, 이미숙 | 박사과정: 강민경, 김혜진, 류혜진, 남서희
석사과정: 송행은, 이규호, 최정은, 정재우, 김지언, 정진규 | 행정직원: 장기쁨