The purpose of my research is to contribute to the conservation of biodiversity by providing knowledge about conservation and restoration of plant species through basic ecology and population genetic studies.

To achieve this goal, the ongoing research in my lab is to infer changes in past population size and estimate historical and contemporary gene flow (seed or pollen) between populations of rare and endangered plant species using allozymes, microsatellites (SSRs), and single nucleotide polymorphisms (SNPs) as molecular markers.

As in multicellular organisms, the unicellular eukaryotic microorganism Saccharomyces cerevisiae is subjected to stress-induced programmed cell death (PCD). We are studying on the mechanism of the stress-induced PCD in the yeast cells lacking the enzymes involved in TCA cycle or glutamate metabolism, e.g., citrate synthase and glutamate dehydrogenase. We also concentrate our efforts on developing the yeast model of metabolic diseases caused by malfunctioning of the TCA cycle or glutamate metabolism.

The filamentous fungus A. nidulans has two distinct types of reproductive event, asexual and sexual cycles, which offer many common developmental themes. To understand the molecular genetic and biochemical mechanism governing the whole process of the life cycle, we have performed global gene expression profiling and cluster analysis of A. nidulans during vegetative growth and sexual/asexual differentiation. On the basis of the transcriptome profiling, we are performing functional characterization of several novel putative transcription factors expected to be involved in sexual/asexual differentiation and secondary metabolite production.

Breast cancer is currently diagnosed on the basis of several histopathological features including tumor size, grade, and lymph node status. In addition, hormone receptors (ER, PR) and HER2 expression in tumors are used to classify and monitor its severity and progression. Despite these common biomarker analyses and the information they provide regarding the molecular features and stage of breast tumors, there remains an unmet need for novel diagnostic and prognostic biomarkers for breast cancer with improved sensitivity and specificity. We have developed a novel breast cancer biomarker, MCB-MD2, useful for qRT-PCR-based diagnosis. Currently, we are performing characterization of MCB-MD2 as the novel tumor suppressor in breast cancer.

We are conducting a systematic zebrafish knockout project to validate candidate genes for mental disorders, including autism. Knockout (KO) zebrafish for the Miles-Carpenter syndrome gene (ZC4H2) were created and KO animal exhibited abnormal swimming, defective eye movement and pectoral fin contractures. We observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specific markers showed a specific loss of V2 interneurons in the brain and spinal cord. Loss of function of ZC4H2 thus likely results in altered connectivity of neuronal circuits, infantile spasm and intellectual disability. The second case is related to autism spectrum disorders (ASDs). ASDs comprise a wide range of neurodevelopmental disorders, characterized by deficits in social behavior, along with repetitive behaviors and impaired communication. Though the exact causes for ASD remain poorly understood, genetic mutations resulting in altered gene function have been implicated causally in ASD. Intragenic mutations in DYRK1A, which have been shown previously to be associated with clinical aspects of Down syndrome, have been associated recently with microcephaly and ASD-like symptoms. We provide a case study of an individual with a 21kb microdeletion within the DYRK1A locus, who has both microcephaly and ASD. We show that dyrk1aa KO fish have microcephaly and impaired social interactions through two newly developed behavioral tests: social interaction and shoaling assays. Also, we confirmed that behavior analysis for ASD through our dyrk1aa KO zebrafish is experimentally tractable, and propose these social behavioral assay methods in zebrafish as a tool for the widespread study of ASD candidate genes.

Control of mRNA translation, stability, and subcellular location is a key aspect of gene expression regulation in eukaryotic cells. We are interested in unveiling the regulatory roles of mRNA decapping activators (Dhh1, Edc3, Scd6, Pat1, Lsm1), or translation initiation factors (Caf20, Eap1). Specific mRNAs, including Ste12 transcription factor or Cln1 cell-cycle regulator, which are preferentially regulated at the translation level during yeast mating or filamentous growth pathway, are targets of our investigation.

Yeast Loc1 and Puf6 are well-known factors for the asymmetric translation of ASH1 mRNA at the bud tip of daughter cells. We observed that Loc1 and Puf6 also regulate the translation of Ste12 transcription factor. Our current interests are to investigate the localization of Ste12 protein and mRNAs during mating processes. Functional association of Loc1 and Puf6 proteins with Dhh1 decapping activator is under investigation.

Under various stress conditions, mRNAs assemble into non-translating mRNPs, which can concentrate in cytoplasmic mRNA granules known as processing bodies (P-bodies) or stress granules. mRNAs in these granules can either be degraded or stored for later translation. The virulence conditions responsible for C. albicans pathogenicity are very much relevant to P-body formation. The core components of P-bodies, Dcp2, Dhh1, Kem1/Xrn1, and Edc3, were identified in C. albicans and their localizations with respect to P-bodies were demonstrated. Deletion of P-body scaffolding protein Edc3 attenuated stress-induced responses, including cell death and ROS accumulation. Our current interest is to investigate the Edc3-dependent gene expression regulation during yeast apoptosis and filamentous growth.

We have found that abolition of a dual-specificity LAMMER kinase exerts profound effects on differentiation of fission yeast Schizosaccharomyces pombe including oxidative stress response, cell division cycle, mating, and so on. Our recent study also revealed that the LAMMER kinase modulates various cellular events by regulating gene-expression and activity of key regulatory proteins in eukaryotic microorganisms. Recently, we found that the LAMMER kinase regulates G1- to S-phase cell cycle progression at transcriptional as well as post-translational level in the fission yeast. At present, we are trying to understand the molecular mechanisms for G1- to S-phase progression and DNA-damage response mediated by LAMMER kinase in fission yeast.

With the aids of various screening technologies such as proteome, DEG (differentially expressed gene) and real-time PCR analysis, we have identified developmental stage-specific genes possibly modulated by the regulatory factors, VeA, NsdD, and etc. in the model filamentous fungus Aspergillus nidulans. At present we are attempting several approaches such as forced mass mating and phospho-proteome analyses to identify novel factors for sexual development in opportunistic human pathogen Aspergillus fumigatus. We are performing the gene disruption with CRISPR/Cas9, suppression test, protein-protein interaction, and morphogenetic analyses in order to characterize function of the genes and regulation mode of gene-expressions in Aspergillus spp.

Human hepatitis B virus (HBV) is a major pathogen for liver diseases including cirrhosis and hepatocellular carcinoma. Among the HBV proteins, X protein plays critical roles in HBV replication and liver oncogenesis. However, the promiscuous functions of HBx are not elucidated yet. We are trying to validate the various regulatory functions of HBx protein in transcriptional transactivation, signal transduction, and carcinogenesis.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus which causes a variety of diseases in human. Among immediate early proteins of HSV-1, ICP27 is essential for viral replication and has multiple functions at transcriptional and post-transcriptional levels. We are dissecting the functional mechanism of ICP27 in the regulation of signal transduction, apoptosis, and viral reactivation. In addition, we also carry the functional analysis of ICP22 and glycoproteins of HSV-1.

Ribozymes are catalytic RNA molecules which bind target RNA sequences and cleave them in a sequence specific manner. We are developing the highly efficient ribozymes which are suppressing the specific viral gene expressions.

Prof. Kim is interested in understanding the molecular mechanisms of cell polarity, especially the signaling pathways for the morphogenetic change during cellular differentiation and development.

• Hippocampal neurons:

  He studies the molecular functions of GEFs or GAPs for Rho GTPases and their regulatory or effector proteins affecting the formation of dendrites or spines in hippocampal neurons.

• Yeast:

  He also investigates the roles of the NDR kinase (Cbk1) and its downstream effectors in morphogenesis and interaction of Candida albicans with intestinal epithelial cells.

Prof. Kim’s research includes the study on the roles of Sirtuin proteins, which belong to a class III histone deacetylase, in cellular aging process.

• Neuronal stem cells:

  He is keen on investigating the mechanisms by which sirtuins regulate aging of neuronal stem cells.

• Yeast:

  He has been studying how Sir2 regulates yeast aging process in response to environmental and metabolic stresses and how Sir2 interacts with key kinases, such as TOR and PKA, in nutrient signaling pathways.

My research interests are focused on the ‘Diversity and Functions of Prokaryotes in Environment’, which include the following areas.

Taxonomy, diversity, evolution and bioactive compounds of filamentous actinobacteria, in particular Streptomyces family

Genome analysis and comparative genomics of prokaryotes, with particular emphasis on filamentous actinobacteria, producers of bioactive compounds and also on acidophilic species

Taxonomic characterization of prokaryotes in natural environment, and description of novel taxa using polyphasic and multigene approaches.

Analysis of prokaryotic diversity using next-generation sequencing (NGS) technology, identification of 'core microbiome', and elucidation of its functions based on genomic and transcriptomic approaches

My research interests are focused on the ‘Diversity and Functions of Prokaryotes in Environment’, which include the following areas.

To identify new cancer drug targets, we examined global changes in gene expression between tumor biopsies and normal tissues. Several unknown genes were identified as genes exhibiting significant differential expression in multiple human cancer tissues. Among those, we identified a gene, Cancer- upregulated gene 2 (CUG2), which is significantly up-regulated in several human tissues such as ovary and liver. Recent our studies also revealed that CUG2 play multiple roles by interacting with various key proteins including CENP-T, an important regulator in the interaction between kinetochore and mitotic spindle during mitosis, and CSN5, a key regulator in the proteasome-mediated protein degradation. CUG2 may play important regulatory roles in cell division and mitosis by modulating the cellular activities of these interacting proteins. Our goal is to investigate the cellular function of the newly-identified cancer-related genes in tumor biogenesis and to develop potentially promising new targets for cancer therapy.

We newly identified a gene, neuronal growth regulator 1 (NEGR1), which displayed commonly down-regulated expression in multiple tumor biopsies. This protein is identified as GPI-anchored protein and localized in lipid raft subcompartment of the cell membrane. Recent reports revealed that the genetic variation of human NEGR1 is highly associated with the human overweight. By using NEGR1 knockout mice, we currently investigate the cellular function of human NEGR1 to reveal the molecular basis of the link between NEGR1 and human obesity and to validate NEGR1 as a future anti-obesity drug target.

The term "Osteoimmunology" has been coined to encourage an interdisciplinary approach to understanding the cross-talk between bone and the immune system. Despite extensive cross-talk between bone metabolism and the immune system, the mechanisms by which one regulates the other, and the biological implications of such interactions, are poorly understood. It has recently come to be appreciated that the skeletal and immune systems regulate each other to a much greater degree than previously believed. In particular, various pathological conditions which lead to excessive bone loss, such as rheumatoid arthritis, osteoarthritis, periodontal diseases, and some tumor-associated bone abnormalities have been shown to be influenced by cellular components (e.g., T lymphocytes) as well as by soluble factors produced by infiltrating lymphocytes (e.g., interferon produced by infiltrating lymphocytes).


Future preventative treatments for these bone-related diseases that impact the quality of life will require a high degree of specificity and selectivity. In this regard, my research is focused on the molecular analysis of the osteoimmune system. The better understanding of how the osteoimmune system operates in normal and pathological situations is likely to lay the groundwork for future therapies for the variety of diseases that affect both bone and the immune system.

Proteins in plants are used to detect the presence of pathogens and initiate the defense signaling againstinvading pathogens. Because of the deleterious effects in growth and development, the expression levels of Rproteins are tightly controlled in various ways but affected by surrounding environmental conditions. Using SNC1 andRPP4, which encode R proteins with TIR (Toll/Interleukin 1 receptor) domain, we are investigating (1) structuraldeterminants for the functions of these R genes in different growth conditions and (2) the mechanism responsible for SNC1 hypermutation in the bal mutant background after mutagen treatment.

Rapid increase in numbers of plant species with whole genome sequences provides challenges in characterizing thespecificity of evolutionarily related biochemical enzymes. Especially it is true for plants because genome-wideduplication and allopolyploidy leading to functional divergence of related genes, and species-specific biochemicalpathways are widespread in plants.With comparative genomics approach based on the functional information obtained from the model plant Arabidopsisthaliana and other plant species, we are characterizing biochemical specificities of enzymes from Brassicaceaeplants involved in specific steps in sulfur and lipid metabolism.

We focused on the development and application of mass spectrometry-based proteomics techniques to a wide range of biological questions. Our research encompasses the area of bioinformatics and software development, methods development and clinical applications. The integration of all the elements in the proteomics pipeline within one lab facilitates advances in all of them.

• (1) Proteomic Approaches for Biomarker Discovery: Discovering clinical biomarkers and developing disease diagnosis models using artificial intelligence on liquid chromatography and mass spectrometry-based proteome big data.
• (2) Diagnostic LC-MS Assay in Clinical Laboratory: Improving and verifying analytical performance based on LC-MS assays and developing internationally standardized in vitro and companion diagnostic assays with new health technology.
• (3) Software Solution for Big Data Analytics: Developing a tool that can help the clinician’s decision-making process in hospitals using multi-omics big data and artificial intelligence algorithms.

Epigenetics (Chromatin Biology) is a study to understand the mechanisms that cause changes in gene expression regulation and post-transcriptional regulation according to various chemical changes in the genome that occur without changing the DNA sequence by various environmental changes or stimuli. In addition, it is a study to understand various normal biological pathways and mechanisms that cause human diseases according to the causal relationship of these epigenetic changes. My research undertakes a comprehensive and systematic analysis of interdisciplinary approaches such as molecular biochemical, genome-wide (Transcriptomic and Epigenomic analyzes; Nascent RNA-seq [GRO-seq], mRNA-seq, ChIP-seq, and eCLIP-seq), and/or proteomic (Mass-spec based analyses) analysis systems in primary cultured precursor neuron/glia, mouse disease models, or induced pluripotent stem cells (iPSCs) from patient samples, and mouse behavioral analyses to further examine the epigenetic regulatory mechanisms underlying various brain diseases.
(1) Understanding the functional dynamics of various functional regulatory non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), enhancer RNAs (eRNAs), or circular RNAs (circRNAs).
(2) Understanding the role of regulatory ncRNAs and associated epigenetic regulators in triggering various intracellular condensates in the nucleus.
(3) Understanding the function of modifications/ de-modifications on RNAs and epigenetic regulators.
(4) Understanding the functional regulatory mechanisms of histone code interactions and dynamics..