A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

김준대,진석원 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.7

Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical impor-tance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endo-thelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lym-phedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in verte-brates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels.

Zebrafish Crip2 Plays a Critical Role in Atrioventricular Valve Development by Downregulating the Expression of ECM Genes in the Endocardial Cushion

김준대,김혜진,권순일,함형진,김명진,이명철,허태린 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.5

The initial step of atrioventricular (AV) valve development involves the deposition of extracellular matrix (ECM) components of the endocardial cushion and the endocardial-mesenchymal transition. While the appropriately regulated expression of the major ECM components, Versican and Hyaluronan, that form the endocardial cushion is important for heart valve development, the underlying mechanism that regulates ECM gene expression remains unclear. We found that zebrafish crip2 expression is restricted to a subset of cells in the AV canal (AVC) endocardium at 55 hours post-fertilization (hpf). Knockdown of crip2 induced a heart-looping defect in zebrafish embryos, although the development of cardiac chambers appeared to be normal. In the AVC of Crip2-deficient embryos, the ex-pression of both versican a and hyaluronan synthase 2 (has2) was highly upregulated, but the expression of bone morphogenetic protein 4 (bmp4) and T-box 2b (tbx2b) in the myocardium and of notch1b in the endocardium in the AVC did not change. Taken together, these results indicate that crip2 plays an important role in AV valve development by downregulating the expression of ECM components in the endocardial cushion.

Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension

김준대,이아람,최지혜,박영숙,강혜수,장우철,이명숙,김종민 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-

Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH.

Alk3/Alk3b and Smad5 Mediate BMP Signaling during Lymphatic Development in Zebrafish

김준대,김종민 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.3

Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of ad-ditional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

Proper Activity of Histone H3 Lysine 4 (H3K4) Methyltransferase Is Required for Morphogenesis during Zebrafish Cardiogenesis

김준대,김은미,권순일,함형진,이명철,김명진,허태린 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.6

While increasing evidence indicates the important function of histone methylation during development, how this process influences cardiac development in vertebrates has not been explored. Here, we elucidate the functions of two histone H3 lysine 4 (H3K4) methylation enzymes, SMYD3 and SETD7, during zebrafish heart morphogenesis using gene expression profiling by whole mount in situ hybridization and antisense morpholino oligonucleotide (MO)- based gene knockdown. We find both smyd3 and setd7 are highly expressed within developing zebrafish heart and knock-down of these genes led to severe defects in cardiac morphogenesis without altering the expressions pattern of heart markers, including cmlc2, vmhc, and amhc. Furthermore, double knock-down by coinjection of smyd3 and setd7 MOs caused the synergistic defects in heart development. As similar to knock-down effect, overexpression of these genes also caused the heart morphogenesis defect in zebrafish. These results indicate that histone modifying enzymes, SMYD3 and SETD7, appear to function synergistically during heart development and their proper functioning is essential for normal heart morphogenesis during development.

마이크로프로세서 기반 EEFL 인버터 설계

김준대(Jun-dea Kim),조익현(Ig-hyun Cho),이충호(Choong-ho Lee),권창영(Chang-young Kwon),윤동한(Dong-han Yoon) 한국정보기술학회 2007 한국정보기술학회논문지 Vol.5 No.3

Proposed EEFL inverter design method with Dimming control to use microprocessor. Reduce power loss using Energy Recovery method, and design inverter control program that use RS-232 communication. Also, low temperature driving time shortened 50% that use duty variable control.

마이크로프로세서를 이용한 디지탈 제어방식의EEFL Inverter 연구

김준대(Kim jun-dea),조익현(Ig-hyun Cho),이충호(Choong-ho Lee),권창영(Chang-young Kwon),윤동한(Yoon dong-han) 한국정보기술학회 2007 Proceedings of KIIT Conference Vol.2007 No.-

본 논문에서는 마이크로프로세서를 이용하여 Dimming control이 있는 EEFL inverter 설계방법을 제안하였다. EEFL Inverter는 half-bridge 방식을 이용하였으며 마이크로 프로세서로는 Megal28을 사용하였고 프로그램은 C언어를 이용하였으며 제작한 Invertor를 이용하여 효율 실험 및 부하실험을 수행하였다. Design and implementation method of Dimming mode EEFL Inverter using micro-processor is described in this paper. The EEFL Invertor use a half-bridge topology. micro-processor use MEGAl28 and program language use C language. Achieved an efficient experiment and a load experiment using EEFL Inverter that design.

FPGA기반 BLDC 모터 제어 IP 코어 개발

김경석,김현구,박희영,김준대,권영 제어로봇시스템학회 2011 제어로봇시스템학회 국내학술대회 논문집 Vol.2011 No.5

MCU and DSC(or DSP) for a driving unit of Artillery and Naval gun in the defense are not inefficiency because they are lack of flexibility with fixed function and category. Recently, we have researched FPGA for uprising the function of a driving unit and making product life cycle longer in the defense. FPGA, that have parallel architecture, is able to minimize the load of occurring in a computation. We explain how to design BLDC motor control IP of FPGA, and results of the experiment. We have experimented this field for a long time. We expect that FPGA will apply a variety of filed in the defense.

연속 웨이브렛 역변환의 멀티 필터 뱅크 시스템

조익현(Ig-hyun Cho),이충호(Choong-ho Lee),권창영(Chang-young Kwon),김준대(Jun-dea Kim),윤동한(Dong-han Yoon) 한국정보기술학회 2007 Proceedings of KIIT Conference Vol.2007 No.-

이 논문은 신호 f(t)의 실제적인 스케일 정보를 나타내는 웨이브렛 플랜을 중심으로 연속 웨이브렛 역변환의 특성에 대하여 논하였다. 웨이브렛 변환에 비해 역변환의 적용이 상대적으로 미비한 이유는 수치적인 연산의 복잡성에 기인한 것이며, 이 논문은 웨이브렛 역변환의 안정된 복원을 위한 방법에 대하여 연구하였다. 웨이브렛 역변환이 안정적으로 실현될 경우 신호 f(t)에 대한 실제적인 스케일 정보를 지니고있는 웨이브렛 플랜 이라는 새로운 “시간-스케일” 공간을 구할 수 있으며, 이는 완전한 멀티 필터 뱅크 시스템과 동일한 특성을 나타낸다. 즉 연속 웨이브렛 변환을 통해 신호 f(t)의 모든 스케일 성분을 독립적으로 주파수 전체 대역에 걸쳐 분산하고 다시 역변환을 통해 원래의 신호를 복원하는 과정은 필터뱅크이론의 분석(analysis)과 합성(synthesis) 과정과 일치한다. 이 논문에서는 연속 웨이브렛 역변환을 이용하여 “시간-스케일” 필터를 통한 신호 f(t)의 스케일 분해와 웨이브렛 멀티 필터 뱅크이론에 대하여 논하였다. This paper is contribute to Inverse continuous wavelets transform which permits to determine real “time-scale” plan. The application of Inverse wavelets transform is not yet represented because of the numerical difficulty. If the signal can be reconstructed stably by Inverse Continuous Wavelets Transform, the multi scale filter bank system which composed by analysis and synthesis process can be designed. In this work, we represent the Inverse Continuous Wavelets Transform which leads to nearly perfect reconstruction of signal and the multi-scale filter bank system.

Full-HD AC PDP 구동파형에 대한 연구

권창영(Chang-young Kwon),조익현(Ig-hyun Cho),이충호(Choong-ho Lee),김준대(Jun-dea Kim),윤동한(Dong-han Yoon) 한국정보기술학회 2007 Proceedings of KIIT Conference Vol.2007 No.-

본 논문은 Full-HID AC PDP 구동에 있어서 새로운 구동파형을 제안한다. 제안된 구동파형은 AC PDP의 선택적 기입(selective writing)구동방식에 기반으로 패널 구조적 변경 없이 (l920×1080 pixels) Full-HD 패널을 구동할 수 있다. 종래의 구동파형은 셀을 초기화 하기 위해서 한 프레임 내에 매 서브필드마다 리셋구간에서 Positive 약방전과 Negative 약방전을 하기 위해서 램프파를 인가하는 구동파형에서 제안된 구동파형은 첫 서브필드에서는 종래의 셀 초기화 방식을 이용하며 나머지 서브필드는 Negative 약방전 과 세폭약방전을 이용하여 고속 어드레스 방전을 실현시킨 구동파형이다. 실험결과 종래의 구동파형은 스캔 펄스폭을 1.2us이하로 FHD AC-PDP 구동이 불가능한 반면 제안된 구동파형은 5000:1의고명암비를 구현과 동시에 어드레스 펄스폭을 0.7us에서 구동할 수 있다. This paper proposes a driving waveform for Full-HD AC plasma display panel(PDP) with a significantly reduced scan time. The proposed driving waveform is based on the selective writing method for driving an AC PDP, and can drive an Full-HD(l920×l080pixels) AC PDP without physically modifying the panel structure. For the conventionall driving waveform, all PDPcells are reset by the ramp waveform with positive dark discharge and negative dark discharge, during all sub-fields of one frame. For the proposed driving waveform, during the first sub-field of one frame, all PDP cells are reset by the conventional ramp waveform during the other sub-fields, all cells is reset by negative dark discharge and a narrow weak discharge. The conventional driving waveform is difficult to drive Full-HD AC PDP within 1.2us scan width, otherwhile the proposed driving waveform can realize to drive Full-HD AC PDP using scan pulse width as narrow as 0.7us with 5000:1 high contrast ratio.