Microengineered Biomimicry of Human Physiological Systems

Dongeun HUH 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10

Microengineered Biomimicry of Human Physiological Systems

Dongeun HUH 한국생물공학회 2020 한국생물공학회 학술대회 Vol.2020 No.10

Microengineered Physiological Biomimicry: Human Organs-on-Chips

Dan Dongeun HUH 한국생물공학회 2019 한국생물공학회 학술대회 Vol.2019 No.4

가축에서 분리된 Vancomycin 내성 장구균의 내성유전자 구조 분석을 통한 분자생물학적 역학 연구

허지영,이선민,이석호,이위교,용동은,이경원,신완식,이동건 대한임상미샐물학회 2003 Annals of clinical microbiology Vol.6 No.2

Organomimetic Microsystems Technologies

박지흠,Dongeun Huh,김광복,이정철,Hee Chan Kim 대한의용생체공학회 2012 Biomedical Engineering Letters (BMEL) Vol.2 No.2

Microscale engineering technologies derived from the semiconductor and microelectronics industries provide new opportunities in biology to create and precisely control threedimensional cell culture microenvironments in a physiologically relevant and organ-specific context. Here we review recent advances in the development of ‘Organs-on-Chips’ in which microsystems technologies have been applied to develop cell culture systems that recapitulate the structural, biochemical,and mechanical characteristics of living organs in order to mimic their complex physiology in vitro. We highlight these new capabilities and advantages enabled by microengineered tissue and organ mimics to show their potential as robust alternatives to conventional two- and three-dimensional cell culture systems, as well as a potential replacement for animal models. We also discuss how this biomimetic microengineering approach is beginning to meet challenges in drug development and environmental testing.

Generalized On-Demand Production of Nanoparticle Monolayers on Arbitrary Solid Surfaces via Capillarity-Mediated Inverse Transfer

Chang, Jeehan,Lee, Jaekyeong,Georgescu, Andrei,Huh, Dongeun,Kang, Taewook American Chemical Society 2019 Nano letters Vol.19 No.3

<P>Century-old Langmuir monolayer deposition still represents the most convenient approach to the production of monolayers of colloidal nanoparticles on solid substrates for practical biological and chemical-sensing applications. However, this approach simply yields arbitrarily shaped large monolayers on a flat surface and is strongly limited by substrate topography and interfacial energy. Here, we describe a generalized and facile method of rapidly producing uniform monolayers of various colloidal nanoparticles on arbitrary solid substrates by using an ordinary capillary tube. Our method is based on an interesting finding of inversion phenomenon of a nanoparticle-laden air-water interface by flowing through a capillary tube in a manner that prevents the particles from adhesion to the capillary sidewall, thereby presenting the nanoparticles face-first at the tube’s opposite end for direct and one-step deposition onto a substrate. We show that our method not only allows the placement of a nanoparticle monolayer at target locations of solid substrates regardless of their surface geometry and adhesion but also enables the production of monolayers containing nanoparticles with different size, shape, surface charge, and composition. To explore the potential of our approach, we demonstrate the facile integration of gold nanoparticle monolayers into microfluidic devices for the real-time monitoring of molecular Raman signals under dynamic flow conditions. Moreover, we successfully extend the use of our method to developing on-demand Raman sensors that can be built directly on the surface of consumer products for practical chemical sensing and fingerprinting. Specifically, we achieve both the pinpoint deposition of gold nanoparticle monolayers and sensitive molecular detection from the deposited region on clothing fabric for the detection of illegal drug substances, a single grain of rice and an orange for pesticide monitoring, and a $100 bill as a potential anti-counterfeit measure, respectively. We believe that our method will provide unique opportunities to expand the utility of colloidal nanoparticles and to greatly improve the accessibility of nanoparticle-based sensing technologies.</P> [FIG OMISSION]</BR>

Organs-on-chips at the frontiers of drug discovery

Esch, Eric W.,Bahinski, Anthony,Huh, Dongeun Nature Publishing Group, a division of Macmillan P 2015 Nature reviews. Drug discovery Vol.14 No.4

Improving the effectiveness of preclinical predictions of human drug responses is critical to reducing costly failures in clinical trials. Recent advances in cell biology, microfabrication and microfluidics have enabled the development of microengineered models of the functional units of human organs — known as organs-on-chips — that could provide the basis for preclinical assays with greater predictive power. Here, we examine the new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening. We also discuss emerging drug discovery opportunities enabled by organs-on-chips, as well as important challenges in realizing the full potential of this technology.

Organ-on-a-chip technology for nanoparticle research

Kang Shawn,Park Sunghee Estelle,Huh Dan Dongeun 나노기술연구협의회 2021 Nano Convergence Vol.8 No.20

The last two decades have witnessed explosive growth in the field of nanoengineering and nanomedicine. In particular, engineered nanoparticles have garnered great attention due to their potential to enable new capabilities such as controlled and targeted drug delivery for treatment of various diseases. With rapid progress in nanoparticle research, increasing efforts are being made to develop new technologies for in vitro modeling and analysis of the efficacy and safety of nanotherapeutics in human physiological systems. Organ-on-a-chip technology represents the most recent advance in this effort that provides a promising approach to address the limitations of conventional preclinical models. In this paper, we present a concise review of recent studies demonstrating how this emerging technology can be applied to in vitro studies of nanoparticles. The specific focus of this review is to examine the use of organ-on-a-chip models for toxicity and efficacy assessment of nanoparticles used in therapeutic applications. We also discuss challenges and future opportunities for implementing organ-on-a-chip technology for nanoparticle research.

Src-mediated phosphorylation of βPix-b regulates dendritic spine morphogenesis

Shin, Mi-seon,Song, Sang-ho,Shin, Jung Eun,Lee, Seung-Hye,Huh, Sung-Oh,Park, Dongeun The Company of Biologists Ltd. 2019 Journal of cell science Vol.132 No.5

<P>PAK-interacting guanine nucleotide exchange factor (βPix; also known as Arhgef7) has been implicated in many actin-based cellular processes, including spine morphogenesis in neurons. However, the molecular mechanisms by which βPix controls spine morphology remain elusive. Previously, we have reported the expression of several alternative spliced βPix isoforms in the brain. Here, we report a novel finding that the b isoform of βPix (βPix-b) mediates the regulation of spine and synapse formation. We found that βPix-b, which is mainly expressed in neurons, enhances spine and synapse formation through preferential localization at spines. In neurons, glutamate treatment efficiently stimulates Rac1 GEF activity of βPix-b. The glutamate stimulation also promotes Src-mediated phosphorylation of βPix-b in both an AMPA receptor- and NMDA receptor-dependent manner. Tyrosine 598 (Y598) of βPix-b is identified as the major Src-mediated phosphorylation site. Finally, Y598 phosphorylation of βPix-b enhances its Rac1 GEF activity that is critical for spine and synapse formation. In conclusion, we provide a novel mechanism by which βPix-b regulates activity-dependent spinogenesis and synaptogenesis via Src-mediated phosphorylation.</P><P><B>Summary:</B> Src-mediated phosphorylation at tyrosine 598 of βPix-b, a major neuronal βPix isoform, regulates its guanine nucleotide exchange factor activity that is critical for spine and synapse formation.</P>

Development of a One-Step Multiplex PCR Assay for Differential Detection of Major <i>Mycobacterium</i> Species

Chae, Hansong,Han, Seung Jung,Kim, Su-Young,Ki, Chang-Seok,Huh, Hee Jae,Yong, Dongeun,Koh, Won-Jung,Shin, Sung Jae American Society for Microbiology 2017 Journal of clinical microbiology Vol.55 No.9

<P>The prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to (i) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750, (ii) differentiate M. tuberculosis (M. tuberculosis) from MTBC using RD9, (iii) selectively identify the widespread M. tuberculosis Beijing genotype by targeting mtbk_20680, and (iv) simultaneously detect five clinically important NTM (M. avium, M. intracellulare, M. abscessus, M. massiliense, and M. kansasii) by targeting IS1311, DT1, mass_3210, and mkan_rs12360. An initial evaluation of the multiplex PCR assay using reference strains demonstrated 100% specificity for the targeted Mycobacterium species. Analytical sensitivity ranged from 1 to 10 pg for extracted DNA and was 10(3) and 10(4) CFU for pure cultures and nonhomogenized artificial sputum cultures, respectively, of the targeted species. The accuracy of the multiplex PCR assay was further evaluated using 55 reference strains and 94 mycobacterial clinical isolates. Spoligotyping, multilocus sequence analysis, and a commercial real-time PCR assay were employed as standard assays to evaluate the multiplex PCR assay with clinical M. tuberculosis and NTM isolates. The PCR assay displayed 100% identification agreement with the standard assays. Our multiplex PCR assay is a simple, convenient, and reliable technique for differential identification of MTBC, M. tuberculosis, M. tuberculosis Beijing genotype, and major NTM species.</P>