Janghwan Kim

Korea Research Institute of Bioscience and Biotechnology KRIBB | KRIBB · Stem Cell Convergenece Research Center (SCRC)

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxi...

Amphibians and fish show considerable regeneration potential via dedifferentiation of somatic cells into blastemal cells. In terms of dedifferentiation, in vitro cellular reprogramming has been proposed to share common processes with in vivo tissue regeneration, although the details are elusive. Here, we identified the cytoskeletal linker protein d...

Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletion, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, a defect in SMN2 splicing, involving exon 7 skipping, results in a low level of functional SMN protein. Therefore, the upregulation of SMN protein expression from the SMN...

Human pluripotent stem cell (hPSC)-derived organoids and cells have similar characteristics to human organs and tissues. Thus, in vitro human organoids and cells serve as a superior alternative to conventional cell lines and animal models in drug development and regenerative medicine. For a simple and reproducible analysis of the quality of organoi...

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of familial Parkinson's disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors...

Advanced technologies are required for generating human intestinal epithelial cells (hIECs) harboring cellular diversity and functionalities to predict oral drug absorption in humans and study normal intestinal epithelial physiology. We developed a reproducible two-step protocol to induce human pluripotent stem cells to differentiate into highly ex...

Parkinson’s disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in repr...

Direct neural reprogramming involves a rapid conversion of somatic cells into neural cells without passing through the intermediate pluripotent stage. This phenomenon can be mediated in the starting somatic cells by the introduction of lineage-specific master transcription factors or by pluripotency factors routinely used in iPS cell generation. In...

Although brain organoids are an innovative technique for studying human brain development and disease by replicating the structural and functional properties of the developing human brain, some limitations such as heterogeneity and long-term differentiation (over 2 months) impede their application in disease modeling and drug discovery. In this stu...

Human pluripotent stem cell (hPSC)-derived organoids and differentiated cells have similar characteristics, such as cell types, structure, and functions, to human organs and tissues. Thus, in vitro human organoids and tissue-specific cells serve as a superior alternative to conventional cell lines and animal models in drug development and regenerat...

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotect...

Lactobacilli, which are probiotic commensal bacteria that mainly reside in the human small intestine, have attracted attention for their ability to exert health-promoting effects and beneficially modulate host immunity. However, host epithelial-commensal bacterial interactions are still largely unexplored because of limited access to human small in...

Background: α-Synuclein (α-syn) is a major component of Lewy bodies, a pathologic marker of Parkinson's disease (PD) in post-mortem studies. The use of α-syn as a practical PD biomarker has been investigated by numerous researchers. However, reports of differences in α-syn levels in bio fluids, such as cerebrospinal fluid, plasma, and saliva, betw...

The diagnosis of Parkinson’s disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However,...

Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that lacks satisfactory treatment. In this...

Current cerebral organoid technology provides excellent in vitro models mimicking the structure and function of the developing human brain, which enables studies on normal and pathological brain; however, further improvements are necessary to overcome the problems of immaturity and dearth of non-parenchymal cells. Vascularization is one of the majo...

Human induced pluripotent stem cells (hiPSCs) are reprogrammed from somatic cells and are regarded as promising cell sources for regenerative medicine and disease research. Recently, techniques for analyses of individual cells, such as single-cell RNA-sequencing and mass cytometry, have been used to understand the stem-cell reprogramming process in...

Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient...

In Parkinson's disease (PD) research, human neuroblastoma and immortalized neural cell lines have been widely used as in vitro models. The advancement in the field of reprogramming technology has provided tools for generating patient- specific induced pluripotent stem cells (hiPSCs) as well as human induced neuronal progenitor cells (hiNPCs). These...

Human intestinal organoids (hIOs), which resemble the human intestine structurally and physiologically, have emerged as a new modality for the study of the molecular and cellular biology of the intestine in vitro. We recently developed an in vitro maturation technique for generating functional hIOs from human pluripotent stem cells (hPSCs). Here, w...

Background & aims: The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripot...

Using genetic engineering to convert cells into stem cells without leaving unwanted foreign DNA behind is made easier and more effective by a method that allows cells acquiring unwanted DNA to be selectively killed. Janghwan Kim, Mi-Young Son and colleagues at the Korea Research Institute of Bioscience and Biotechnology, Daejeon, included a cell “s...

Short‑chain fatty acids (SCFAs; butyrate, propionate and acetate) are metabolites derived from the gut microbiota via dietary fiber fermentation. In colon cancer, treatment with SCFAs, mainly butyrate and propionate, suppresses cell proliferation, migration and invasion. Furthermore, although sodium butyrate is known to induce cell apoptosis in lun...

Spinal muscular atrophy (SMA) is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Only ∼10% of the products of SMN2, a paralogue of SMN1, are functional full-length SMN (SMN-FL) proteins, whereas SMN2 primarily produces alternatively spliced transcripts lacking exon 7. Reduced SMN protein levels in SMA patients lead to...

The microbiota and bacterial metabolites in the colon are regarded as alternative targets for colon cancer prevention and therapy. Among these metabolites, short-chain fatty acids (SCFAs) exhibit anticancer effects and suppress inflammation in the colon. However, the molecular mechanisms and target development of SCFAs require additional study. In...

A compound that establishes metabolic conditions favorable for sustaining stem cells may also offer a safe drug for promoting hair regrowth. Drugs that inhibit mitochondrial activity help lock stem cells into a pluripotent state that allows them to actively divide and repair various tissues, but many of these drugs are toxic. Researchers led by Myu...

Leucine‐rich repeat kinase 2 (LRRK2) is a causal gene of Parkinson disease. G2019S pathogenic mutation increases its kinase activity. LRRK2 regulates various phenotypes including autophagy, neurite outgrowth, and vesicle trafficking. Leucyl‐tRNA synthetase (LRS) attaches leucine to tRNALeu and activates mTORC1. Down‐regulation of LRS induces autoph...

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism...

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. PD can result from a mutation of alpha-synuclein (α-SNCA), such as α-SNCA A53T. Using episomal vectors, induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts with the α-SNCA A53T mutation. A huge bacterial artificial chromosome (BAC) har...

Lytic induction of latent Epstein-Barr virus (EBV) has been considered as a therapeutic approach for efficient treatment of EBV-associated malignancies. Here, we established a robust assay system quantitatively measuring EBV lytic induction and identified three Euphorbia extracts as strong inducers from a screen of Korean medicinal plant extracts l...

Alternative cell models of human neural stem cells (hNSCs) have been developed and used for investigations ranging from in vitro experiments to in vivo clinical studies. However, a cell model capable of mimicking the 'normal' state of hNSCs is mandatory in order to extrapolate the results of these studies to humans. In the present study, to select...

Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human-induced p...

The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's...

Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic organisms. Even though DGAT2, one of two distinct DGATs, has a vital role in TG biosynthesis, little is known about the regulation of DGAT2 activity. In this study, we examined the role of...

The relative protein amount of wild type and mutant human DGAT2. The band intensity of DGAT2 proteins in Fig 2C was quantified and normalized by the corresponding band intensity of Magoh proteins. The relative protein amount was calculated by setting the value from wild-type human DGAT2 to 1. The mean values and standard deviations were determined...

The effect of ROS and ROS generator on intermolecular disulfide crosslinking of human DGAT1. Membrane extracts from human DGAT1-overexpressing Sf9 insect cells were treated with H2O2 (A) or β-lapachone (B) in the presence or absence of 20 mM DTT and subjected to Western blot analysis using anti-DGAT1 antibody. The amount of monomeric human DGAT1 pr...

The effect of ROS and ROS generator on human DGAT1 catalytic activity. Membrane extracts from human DGAT1-overexpressing Sf9 insect cells were treated with indicated concentrations of H2O2 (A) or β-lapachone (B) in the presence or absence of 20 mM DTT. The activities of membrane extracts treated with PBS (instead of H2O2) or DMSO (instead of β-lapa...

Multimeric complex of human DGAT2 formed by H2O2-induced disulfide crosslinking in HEK293 cells. HEK293 cells were transfected with plasmid overexpressing human DGAT2 for 47 hours and further incubated with indicated concentrations of H2O2 for 1 hour. Cell extracts were harvested in a way described in Materials and Methods section and subjected to...

TLC analysis of intracellular lipids extracted from cells overexpressed with wild-type or mutants human DGAT2. Wild-type or mutants (C87A, C96A, C99A, C172A, C214A, C312A and C0) human DGAT2 were overexpressed in HEK293 cells for 42 hours and incubated in the presence of [14C]-glycerol for additional 6 hours. Intracellular lipids were extracted fro...

Resistance of human GPAT1 activity to thiol-modifying reagents. (A) The effect of NEM and H2O2 on human GPAT1 activity compared to that on human DGAT2. Membrane extracts from human DGAT2- or GPAT1-overexpressing Sf9 insect cells were treated with indicated concentrations of NEM or H2O2. Human DGAT2 and GPAT1 activities were measured by using the co...

Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during...

Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplan...

Aims: The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patien...

The biological applications of vertical nanostructures mostly rely on their intracellular accessibility through the cellular membrane by promoting cell-to-nanostructure interactions. Herein, we report a seemingly counter-intuitive approach for the spontaneous formation of mouse induced pluripotent stem cell (iPSC)-derived three-dimensional spherica...

Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fi...

Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative...

Enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. However, no effective therapy is currently available for the treatment of these infections. We identified gemcitabine, a nucleoside-analog drug used for cancer treatment, from a screen of bioactive...

Background: Leucine-rich repeat kinase 2 (LRRK2) is a gene in which a mutation causes Parkinson's disease (PD), and p53 is a prototype tumor suppressor. In addition, activation of p53 in patient with PD has been reported by several studies. Because phosphorylation of p53 is critical for regulating its activity and LRRK2 is a kinase, we tested whet...

Recent work generating induced dopaminergic (iDA) neurons using direct lineage reprogramming potentially provides a novel platform for the study and treatment Parkinson's disease (PD). However, one of the most important issues for iDA-based applications is the degree to which iDA neurons resemble the molecular and functional properties of their end...

The direct lineage reprogramming of somatic cells to other lineages by defined factors has led to innovative cell-fate-change approaches for providing patient-specific cells. Recent reports have demonstrated that four pluripotency factors (Oct4, Sox2, Klf4, and c-Myc) are sufficient to directly reprogram fibroblasts to other specific cells, includi...

Recently we have witnessed an array of studies on direct reprogramming that describe induced inter conversion of mature cell types from higher organisms including human. While these studies reveal an unexpected level of plasticity of differentiated somatic cells, they also provide unprecedented opportunities to develop regenerative therapies for ma...

This study was undertaken to generate and characterize human induced pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to examine whether these cells can be developed into disease-relevant cell types for use in disease modeling and drug discovery. Human synovial cells isolated from two 71-year-old women with advanced OA were...

Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC differentiation paradigm is the inability to effectively capture and, in the long-term, stably expand p...

The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this proc...

Here we show that conventional reprogramming towards pluripotency through overexpression of Oct4, Sox2, Klf4 and c-Myc can be shortcut and directed towards cardiogenesis in a fast and efficient manner. With as little as 4 days of transgenic expression of these factors, mouse embryonic fibroblasts (MEFs) can be directly reprogrammed to spontaneously...

Document S1. Supplemental Figures, Supplemental Tables, and Supplemental Experimental ProceduresxDownload (1.5 MB ) Document S1. Supplemental Figures, Supplemental Tables, and Supplemental Experimental ProceduresMovie S1. Rhythmically Beating Cardiomyocytes from hiPSC-O Cells after Application of Embryoid Body Differentiation ApproachxDownload (4.0...

Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focu...

Supplemental table. Primers of NOTCH signaling pathway related Human genes for RT-PCR.

The ability to generate neural lineages from human embryonic stem cells (hESCs) in a controlled manner would further investigation of human neurogenesis and development of potential cell therapeutic applications to treat neurological diseases; however, generating such neural stem cells (NSCs) remains a challenge. In an attempt to characterize the c...

Complex signaling pathways operate in human embryonic stem cells (hESCs) and are coordinated to maintain self-renewal and stem cell characteristics in them. Protein tyrosine kinases (PTKs) participate in diverse signaling pathways in various types of cells. Because of their functions as key molecules in various cellular processes, PTKs are anticipa...

Pluripotent human embryonic stem cells (hESCs) have the distinguishing feature of innate capacity to allow indefinite self-renewal. This attribute continues until specific constraints or restrictions, such as DNA methylation, are imposed on the genome, usually accompanied by differentiation. With the aim of utilizing DNA methylation as a sign of ea...