Moo-Yeal Lee

Moo-Yeal Lee
University of North Texas | UNT · Biomedical Engineering

PhD

About

86
Publications
17,515
Reads
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2,352
Citations
Citations since 2016
36 Research Items
1032 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Introduction
Our laboratory is focusing on creating miniaturized tissue constructs containing multiple layers of human cells in biomimetic hydrogels on several chip platforms using microarray 3D bioprinting technology (https://bioprinting.engineering.unt.edu). These 3D-printed mini-tissues with cells obtained from patients can be used as promising disease models for screening therapeutic drugs for individual patients, thereby potentially revolutionizing regenerative medicine, oncology, and drug discovery.
Additional affiliations
July 2021 - July 2021
University of North Texas
Position
  • Professor (Associate)
April 2018 - July 2021
Cleveland State University
Position
  • Professor (Associate)
November 2017 - present
Bioprinting Laboratories, Inc.
Position
  • CEO
Description
  • Bioprinting Labs (BPL) has been commercializing a 384-pillar plate with sidewalls and slits (384PillarPlate), bioprinted human tissues on the 384PillarPlate (TissuePlate), and related toxicity assessment assays.
Education
March 1995 - February 1999
Korea Advanced Institute of Science and Technology
Field of study
  • Chemical and Biomolecular Engineering
March 1993 - February 1995
Korea Advanced Institute of Science and Technology
Field of study
  • Chemical and Biomolecular Engineering
March 1987 - February 1993
Gyeongsang National University
Field of study
  • Chemical Engineering

Publications

Publications (86)
Article
Full-text available
Differential expression of various drug-metabolizing enzymes (DMEs) in the human liver may cause deviations of pharmacokinetic profiles, resulting in interindividual variability of drug toxicity and/or efficacy. Here, we present the 'Transfected Enzyme and Metabolism Chip' (TeamChip), which predicts potential metabolism-induced drug or drug-candida...
Article
Contemporary cancer therapy refers to treatment based on genetic abnormalities found in patient's tumor. However, this approach is faced with numerous challenges, including tumor heterogeneity and molecular evolution, insufficient tumor samples available along with genetic information linking to clinical outcomes, lack of therapeutic drugs containi...
Article
We have developed a novel three-dimensional (3D) cellular microarray platform to enable the rapid and efficient tracking of stem cell fate and quantification of specific stem cell markers. This platform consists of a miniaturized 3D cell culture array on a functionalized glass slide for spatially addressable high-throughput screening. A microarray...
Article
The generation of biological diversity by engineering the biosynthetic gene assembly of metabolic pathway enzymes has led to a wide range of "unnatural" variants of natural products. However, current biosynthetic techniques do not allow the rapid manipulation of pathway components and are often fundamentally limited by the compatibility of new path...
Article
Full-text available
We have developed a miniaturized 3D cell-culture array (the Data Analysis Toxicology Assay Chip or DataChip) for high-throughput toxicity screening of drug candidates and their cytochrome P450-generated metabolites. The DataChip consists of human cells encapsulated in collagen or alginate gels (as small as 20 nl) arrayed on a functionalized glass s...
Article
Neurological diseases are caused by defects in the brain, spinal cord, or nervous system. Excluding animal models, ex vivo brain tissues and brain organoids have been used for modeling neurological diseases. In addition, the blood–brain barrier (BBB) is a selective semipermeable membrane that separates the peripheral blood from the neural tissue. T...
Article
Neurotoxicity potential of compounds by inhibition of ion channels and efflux transporters has been studied traditionally using two-dimensionally (2D) cultured cell lines such as CHO and HEK-293 overexpressing the protein of interest. However, these approaches are time consuming and do not recapitulate the activity of ion channels and efflux transp...
Article
Full-text available
3D cardiac engineered constructs have yielded not only the next generation of cardiac regenerative medicine but also have allowed for more accurate modeling of both healthy and diseased cardiac tissues. This is critical as current cardiac treatments are rudimentary and often default to eventual heart transplants. This review serves to highlight the...
Article
Three-dimensional (3D) cell culture in vitro has proven to be more physiologically relevant than two-dimensional (2D) culture of cell monolayers, thus more predictive in assessing efficacy and toxicity of compounds. There have been several 3D cell culture techniques developed, which include spheroid and multicellular tissue cultures. Cell spheroids...
Article
Assessing the neurotoxicity of test chemicals has typically been performed using two-dimensionally (2D)-cultured neuronal cell monolayers and animal models. The in vitro 2D cell models are simple and straightforward compared to animal models, which have the disadvantage of being relatively low throughput, expensive, and time consuming. Despite thei...
Article
Full-text available
A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA deto...
Article
It is challenging to rapidly identify immune responses that reflect the state and capability of immune cells due to complex heterogeneity of immune cells and their plasticity to pathogens and modulating molecules. Thus, high-throughput and easy-to-use cell culture and analysis platforms are highly desired for characterizing complex immune responses...
Article
The assessment of neurotoxicity has been performed traditionally with animals. However, in vivo studies are highly expensive and time-consuming, and often do not correlate to human outcomes. Thus, there is a need for cost-effective, high-throughput, highly predictive alternative in vitro test methods based on early markers of mechanisms of toxicity...
Chapter
A variety of oxidative and conjugative enzymes are involved in the metabolism of compounds including drugs, which can be converted into toxic metabolites by Phase I drug-metabolizing enzymes (DMEs), such as the cytochromes P450 (CYP450s), and/or detoxified by Phase II DMEs, such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and...
Article
Full-text available
Conventional in vitro toxicity studies have focused on identifying IC50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain understudied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organi...
Article
Today one out of six children are diagnosed with developmental disorders and there is a critical need to screen compounds such as environmental toxicants and pharmaceutical drugs for their potential developmental toxicity. It is widely accepted that developing central nervous system is highly susceptible to damage by exposure to toxicants due to th...
Article
High-content imaging (HCI) assays on two-dimensional (2D) cell cultures often do not represent in vivo characteristics accurately, thus reducing the predictability of drug toxicity/efficacy in vivo. On the other hand, conventional 3D cell cultures are relatively low throughput and possess difficulty in cell imaging. To address these limitations, a...
Article
Full-text available
The US Environmental Protection Agency (EPA) launched the Transform Tox Testing Challenge in 2016 with the goal of developing practical methods that can be integrated into conventional high-throughput screening (HTS) assays to better predict the toxicity of parent compounds and their metabolites in vivo. In response to this need and to retrofit exi...
Article
Numerous chemicals including environmental toxicants and drugs have not been fully evaluated for developmental neurotoxicity. A key gap exists in the ability to predict accurately and robustly in vivo outcomes based on in vitro assays. This is particularly the case for predicting the toxicity of chemicals on the developing human brain. A critical n...
Article
For better mimicking tissues in vivo and developing predictive cell models for high-throughput screening (HTS) of potential drug candidates, three-dimensional (3D) cell cultures have been performed in various hydrogels. In this study, we have investigated several polymer coating materials to robustly attach PuraMatrix peptide hydrogel on a micropil...
Article
Full-text available
Human liver contains various oxidative and conjugative enzymes that can convert nontoxic parent compounds to toxic metabolites or, conversely, toxic parent compounds to nontoxic metabolites. Unlike primary hepatocytes, which contain myriad drug-metabolizing enzymes (DMEs), but are difficult to culture and maintain physiological levels of DMEs, immo...
Article
The majority of high-content imaging (HCI) assays have been performed on two-dimensional (2D) cell monolayers for its convenience and throughput. However, 2D-cultured cell models often do not represent the in vivo characteristics accurately and therefore reduce the predictability of drug toxicity/efficacy in vivo. Recently, three-dimensional (3D) c...
Article
Full-text available
Tumor spheroids are multicellular, three-dimensional (3D) cell culture models closely mimicking the microenvironments of human tumors in vivo, thereby providing enhanced predictability, clinical relevancy of drug efficacy and the mechanism of action. Conventional confocal microscopic imaging remains inappropriate for immunohistological analysis due...
Article
Full-text available
Layer-by-layer cell printing is useful in mimicking layered tissue structures inside the human body and has great potential for being a promising tool in the field of tissue engineering, regenerative medicine, and drug discovery. However, imaging human cells cultured in multiple hydrogel layers in 3D-printed tissue constructs is challenging as the...
Article
Neural progenitor cell (NPC) fate is influenced by a variety of biological cues elicited from the surrounding microenvironment and recent studies suggest their possible role in pediatric glioblastoma multiforme (GBM) development. Since a few GBM cells also display NPC characteristics, it is not clear whether NPCs transform to tumor cell phenotype l...
Article
Horseradish peroxidase was chemically modified with comb-shaped polymaleic anhydride-alt-1-tetradecene (PMA-TD) in microemulsion systems to produce surface-active peroxidase that has capability to form micellar structures in aqueous solutions and can be concentrated at liquid/liquid interfaces without unfolding of the enzyme. For chemical modificat...
Article
Full-text available
Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosync...
Chapter
Acquiring high-content images of 3D-cultured cells for analyzing multiple cellular events is a daunting task, requiring an automated fluorescent microscope and high-throughput image analysis software. High throughput is an important feature for high-content imaging (HCI) devices to enable rapid image acquisition. Various factors come into play when...
Chapter
Microarray bioprinting refers to printing extremely small amounts of biological samples in patterns on a chip platform, such as functionalized silicone wafers, glass slides, and plastic chips [1, 2]. This technology is mostly based on inkjet printing technologies that allows nanoliter droplet dispensing in high throughput to deposit and pattern bio...
Chapter
Applications for microarray bioprinting include compound toxicity and efficacy assessments, disease diagnostics, and simulation of tissue microenvironments on a small scale. The low volume, high-throughput nature of this system makes it ideal for rapid screening and assay development, particularly in regards towards assays that can be used on vario...
Chapter
Fluorescence-based cell imaging is an important technology for analyzing various biological processes at cellular and molecular levels [1]. Morphological and functional features in a cell can be labeled with multiple fluorescent probes/reagents, imaged with automated fluorescence microscopes, and quantified with image analysis algorithms [2]. In pa...
Chapter
The early stages of drug discovery heavily rely on high-throughput screening (HTS) of compound libraries to identify effective lead compounds. Biochemical and cell-based assays have been commonly performed with the assistance of robotic liquid dispensing systems to rapidly test and identify the potential efficacy and toxicity of drug candidates [1,...
Chapter
High-content imaging (HCI) and image processing of cells grown in 3D pose a significant challenge because 3D cells are not grown in a single focal plane, and the cell culture systems are often incompatible with traditional microscopes. Confocal microscopy is an important tool for imaging 3D cells due to its ability to acquire high definition images...
Chapter
There are three significant types of platforms used in microarray printing technology: glass slides, micropillar chips, and microwell chips. The surfaces of these platforms are treated for different applications. For example, a glass slide is ideal for micropatterning and can be used for microscopic image analysis. Micropillar and microwell chips a...
Chapter
Microarray spotters equipped with solenoid valves are capable of printing a wide range of biological samples, including reagents, growth media, compounds, hydrogels, genes, proteins, viruses, and cells, for biochemical and cell-based assays. Solenoid valve-driven bioprinting has clear advantages over other printing technologies in terms of controll...
Article
Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3 B human hepatoma cells in algina...
Article
Three-dimensional (3D) cancer cell culture models mimic the complex 3D organization and microenvironment of human solid tumor tissue and are thus considered as highly predictive models representing avascular tumor regions. Confocal laser scanning microscopy is useful for monitoring drug penetration and therapeutic responses in 3D tumor models; howe...
Chapter
Exposure to environmental toxicants such as heavy metals, pesticides, and nanoparticles poses a severe threat to both the developing and the adult human brain, causing various neurodegenerative disorders. Detection and quantification of neurotoxicity induced by such toxicants represent a major challenge due to the complexity of neuronal pathways in...
Article
Full-text available
High content imaging (HCI) is a multiplexed cell staining assay developed for better understanding of complex biological functions and mechanisms of drug action, and it has become an important tool for toxicity and efficacy screening of drug candidates. Conventional HCI assays have been carried out on two-dimensional (2D) cell monolayer cultures, w...
Article
Full-text available
Conventional drug screening processes are a time-consuming and expensive endeavor, but highly rewarding when they are successful. To identify promising lead compounds, millions of compounds are traditionally screened against therapeutic targets on human cells grown on the surface of 96-wells. These two-dimensional (2D) cell monolayers are physiolog...
Article
Full-text available
Area-based and intensity-based 3D cell viability measurement methods are compared in high-throughput screening in order to analyze their effects on the assay results (doubling time and IC50) and their repeatability. Many other 3D cell-based high-throughput screening platforms had been previously introduced, but these had not clearly addressed the e...
Conference Paper
Full-text available
A high-throughput cell printing technology has developed to simulate the liver tissue environment using a hydrogel-based chip platform that has potential to shift in vivo drug toxicity models towards in vitro tests. However, the hydrophobic nature of polystyrene chips is not promoting direct adhesion of hydrogels, which created a problem with spot...
Article
Full-text available
The limiting dilution assay (LDA) is a clonogenic drug efficacy test designed to determine a value for drug efficacy based on an all-or-none (positive or negative) response within replicates. It also attempts to calculate minimum cell numbers for cells to form colony in each drugged conditions, wherein a large value implies high drug efficacy (as a...
Article
Full-text available
Similar to what lipase does, a surface-active enzyme was developed by attaching peroxidase on combshaped polymaleic anhydride-alt-1-tetradecene (PMA-TD) in a microemulsion system composed of n-butyl acetate and buffer solution, and its catalytic characteristics of polyphenol synthesis were investigated in an aqueous solution. The modified peroxidas...
Article
Full-text available
The DataChip is a universal platform for three-dimensional (3D) cell cultures on a micropillar chip, which can be applicable to a variety of human cells to simulate organ-specific toxicity. In addition, the MetaChip is developed for various combinations of drug metabolizing enzymes that can be spotted into the microwell chip and incubated with 3D h...
Article
We have developed a plastic pillar insert to facilitate miniaturized three-dimensional (3D) cell cultures in 96-well plates by forming 3D hydrogel droplets containing cells (about 1μL) on the tip of the pillar insert. Hemispherical 3D droplets containing cells were formed simply by immersing the tip of the pillar insert into a mixture of poly-l-lys...
Article
A method for high-throughput retroviral transfection of genes and interfering RNA into 3D cell-culture microarrays is described. 3D cultures more closely mimic the in vivo cellular milieu, thus providing cellular responses to genetic manipulation more similar to the in vivo situation than 2D cultures. This technique is applied to transfect several...
Article
Full-text available
The enormous pool of chemical diversity found in nature serves as an excellent inventory for accessing biologically active compounds. This chemical inventory, primarily found in microorganisms and plants, is generated by a broad range of enzymatic pathways under precise genetic and protein-level control. In vitro pathway reconstruction can be used...
Article
Three-dimensional (3D) cellular assays closely mimic the in vivo milieu, providing a rapid, inexpensive system for screening drug candidates for toxicity or efficacy in the early stages of drug discovery. However, 3D culture systems may suffer from mass transfer limitations, particularly in delivery of large polypeptide or nucleic acid compounds. N...
Article
Full-text available
Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug ca...
Conference Paper
The development of genomic and proteomic technologies has led to the generation of enormous data sets of differentially expressed genes or proteins under varying conditions (e.g. environmental perturbations, cell differentiation, carcinogenesis, etc.) The critical issue is to identify which of these differentially expressed genes play a causal role...
Article
Full-text available
Cytochrome P450 enzyme (CYP450s) assays are critical enzymes in early-stage lead discovery and optimization in drug development. Currently available fluorescence-based reaction assays provide a rapid and reliable method for monitoring CYP450 enzyme activity but are confined to medium-throughput well-plate systems. The authors present a high-through...
Conference Paper
A common in vivo drug-drug interaction is the inhibition of Cytochrome P450 (CYP450) enzymes responsible for drug metabolism, resulting in higher systemic levels of a drug and possible toxicity. Drug-drug interactions represent a safety hurdle and a major expense in drug discovery. Hence it is vital to incorporate in vitro CYP450 inhibition assays...
Conference Paper
Combinatorial chemistry and advances in genomics and proteomics has resulted in a dramatic increase in the number of new chemical entities (NCEs) and screenable drug targets. Nevertheless, these advances have not translated into an increased number of new drug approvals, in part because of the high failure rate due to toxicity of the NCE or its met...
Article
A heparin glycan chip (HepGlyChip) with a 4800-fold enhanced signal-to-noise ratio as compared with the control without heparin was developed for high-throughput analysis of heparin-protein interactions for new drug development and for screening biological samples in diagnostic applications. As a proof of concept, a heparin glycan microarray was pr...
Article
We have developed an immunofluorescence-based assay for high-throughput analysis of target proteins on a three-dimensional cellular microarray platform. This process integrates the use of three-dimensional cellular microarrays, which should better mimic the cellular microenvironment, with sensitive immunofluorescence detection and provides quantita...
Article
Poor drug candidate safety profiles are often identified late in the drug development process, manifesting themselves in the preclinical and clinical phases and significantly contributing to the high cost and low yield of drug discovery. As a result, new tools are needed to accelerate the assessment of drug candidate toxicity and human metabolism e...
Article
The development of a tool that can provide early-stage predictive toxicology data may accelerate the identification of safer drug candidates, and thereby improve the clinical progression of drug candidates to pharmaceuticals. Such a system would require an accurate and reliable technique that is amenable to the large number of drug candidates that...
Article
Chitosan-based polymeric surfactants (CBPSs) were prepared by N-acylation of chitosans (chitosan 10 and 500) with several acid anhydrides such as hexanoic (C6), lauric (C12), and palmitic (C16) anhydrides. Among the CBPS samples, CBPSs having a good solubility at pH 4.0 were selected and observed for viscosity, surface tension, and adsorption of he...