Minoru S.H. Ko

Brief Biography of Minoru S.H. Ko.

Born in Osaka, Japan, in 1961, I became a U.S. citizen in 2004 and now live in Baltimore, Maryland. My scientific career began in 1983, when I started laboratory research as a medical student at Keio University School of Medicine. I received my M.D. in 1986 and Ph.D. in 1991 from Keio. My early career as an independent scientist began at the ERATO Furusawa MorphoGene Project in Tsukuba, where I joined in 1988 and became Group Leader in 1991. In 1992, I moved to the United States to join Wayne State University in Detroit as an Assistant Professor and later became a tenured Associate Professor in 1996. In 1998, I was appointed Senior Investigator and Chief of the Developmental Genomics and Aging Section at the National Institute on Aging, NIH, a tenured position I held in Baltimore until 2012. I then became Professor and Chair of the Sakaguchi Memorial Department of Systems Medicine at Keio University School of Medicine, and Professor Emeritus in 2022. My research is driven by systems thinking, integrating large-scale experimental and informatics approaches, particularly from the perspective of gene networks. I co-founded Elixirgen (2012), Elixirgen Scientific (now Ricoh Biosciences, 2016), and Elixirgen Therapeutics (2017), served as Chief Scientific Officer, authored over 170 peer-reviewed articles, and contributed to the “Stem Cell Biology” chapter in Harrison’s Principles of Internal Medicine (17th–19th eds.). My lifelong aspiration is to develop effective therapies for people suffering from disease.

■ CURRENT POSITIONS
• Chief Scientific Officer, Elixirgen Therapeutics, Inc.
• Professor Emeritus, Keio University

■ OTHER BIOGRAPHICAL LINKS
• Academia Aeterna (Japanese page) https://academia-aeterna.org/m/?MinoruKo3
• Reproductive Biomedicine Online https://www.rbmojournal.com/article/S1472-6483(10)60852-8/fulltext
• LinkedIn https://www.linkedin.com/in/minoru-ko-b46374106
• Keio Researchers Information System https://k-ris.keio.ac.jp/html/100001708_en.html
• Legacy web site of my Keio Lab (2012-2022) https://www.systemsmedicine.jp/en/
• Google Scholar https://scholar.google.com/citations?user=f4D7YvQAAAAJ&hl=en

■ NOTABLE CONTRIBUTIONS TO SCIENCE
• Systems Thinking, Systems Biology, and Systems Medicine (1985-)
• Positive Feedback Gene Expression (1989)
• Stochastic Gene Expression (1990-2012)
• Equalized cDNA Libraries (aka Normalized cDNA Libraries) (1990, 1994)
• Mouse Whole Gene Catalog (1990-2003)
• NIA 15K Mouse cDNA Clone Set (2000)
• NIA 7.4K Mouse cDNA Clone Set (2002)
• NIA Mouse Whole cDNA Microarrays (2000)
• Agilent Mouse Whole cDNA Oligonucleotide Microarrays (2003, 2005)
• Global Gene Expression Patterns in Mouse Preimplantation Embryos (2000, 2004)
• Bioinformatics Tools (2006-)
• Half-lives of All mRNAs in Mouse (2009)
• Systematic Manipulation of Transcription Factors in Mouse ES Cells (2009) and Human ES Cells (2020)
• Transcription Factor mRNA-based Human ES/iPS Cell Differentiation (2011-)
• Controllable Self-replicating RNA (c-srRNA) Vectors (2022-)
• ZSCAN4 Discovery and Characterizations (2007-)


● Systems Thinking, Systems Biology, and Systems Medicine (1985-)
My research is driven by systems thinking, integrating large-scale experimental and information-science approaches to understand biological systems as a whole, particularly from the viewpoint of the network of all genes. Initially, I worked on computer simulations of gene regulatory networks but soon found that there was insufficient quantitative data about gene regulation, gene interactions, network formation, and the structure and dynamics of these networks. Some of my early attempts are described in further detail below in the “Positive Feedback Gene Expression” and “Stochastic Gene Expression” sections.
To enable global gene network analyses, one of the critical technologies that I envisioned was a method to measure the expression levels of all genes. To develop such technologies, I conceived and designed experimental strategies that my lab developed and carried out systematic, genome-scale, large-scale analyses of all mouse genes. Some genes function only in embryos and stem cells, and thus the work heavily focuses on the junction of developmental biology, stem cell biology, and genomics. We thus called this developmental genomics or embryogenomics. These efforts are described further in detail in “Equalized cDNA Libraries,” “Mouse Whole Gene Catalog,” “NIA 15K Mouse cDNA Clone Set,” “NIA 7.4K Mouse cDNA Clone Set,” “NIA Mouse Whole cDNA Microarrays,” “Agilent Mouse Whole cDNA Oligonucleotide Microarrays,” “Global Gene Expression Patterns in Mouse Preimplantation Embryos,” “Bioinformatics Tools,” “Half-lives of All mRNAs in Mouse,” and “Systematic Manipulation of Transcription Factors in Mouse ES Cells and Human ES Cells.”
As my lifelong aspiration is to develop effective therapies for people suffering from disease, I always view these efforts in my research from the perspective of medical research and therapeutic application. For example, my interest in “Positive Feedback Gene Expression” led to the development of “Controllable Self-replicating RNA (c-srRNA) Vectors,” which can potentially be used as a T-cell vaccine.
My research in “Systematic Manipulation of Transcription Factors in Mouse ES Cells and Human ES Cells” led to the development of “Transcription Factor mRNA-based Human ES/iPS Cell Differentiation,” which can be directly applied to regenerative medicine. Therapeutic application of mRNA technologies has become one of my current focused research areas.
My research in systematic large-scale analyses of “Global Gene Expression Patterns in Mouse Preimplantation Embryos” led to the discovery of the ZSCAN4 gene around the early 2000s, which further led us to the discovery of its functions in telomere elongation, genome integrity, karyotype integrity, stem cell aging, and rejuvenation, as described in “ZSCAN4 Discovery and Characterizations.” I am focusing more and more on the therapeutic application of ZSCAN4.

Key References:
• Takano, Ko (1985). Enhancer sequences for gene expression regulation.
• Ko (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs. A quote from the Discussion section, “I expect the current procedure to allow the production of a catalogue of a full set of the genes expressed throughout the life time of any organism. This catalogue could be used to estimate simultaneously the expression levels of most genes using radiolabeled cDNA copies of mRNA at the original abundance as mixed probes and make it possible to identify tissue-specifically expressed genes. It is worth noting that it is more appropriate to use the current short cDNA fragments than full length cDNA species in these applications, since the high sequence specificity of the 3’-framgments should eliminate cross-hybridization of different cDNA species.”
https://pubmed.ncbi.nlm.nih.gov/2216762/
• Schlessinger, Ko (1998). Developmental Genomics and Its Relation to Aging.
https://pubmed.ncbi.nlm.nih.gov/10348638/
• Ko (2001). Embryogenomics: developmental biology meets genomics.
https://pubmed.ncbi.nlm.nih.gov/11711195/
• Ko (2004). Embryogenomics of preimplantation mammalian development: Current Status.
https://pubmed.ncbi.nlm.nih.gov/14972105/
• Tanaka et al. (2004). Genomic approaches to stem cell biology.
• VanBuren, Ko (2004). Principles and Application of Embryogenomics.
• Aiba et al. (2006). Genomic approaches to early embryogenesis and stem cell biology.
https://pubmed.ncbi.nlm.nih.gov/17123228/
• Ko (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions.
https://pubmed.ncbi.nlm.nih.gov/15820015/
• Ko (2006). Expression profiling of the mouse early embryo: Reflections and perspectives.
https://pubmed.ncbi.nlm.nih.gov/16739220/


● Positive Feedback Gene Expression (1989)
I conceived the use of a positive feedback loop to enhance the expression of a transgene in mammalian cells. By designing glucocorticoid receptor production to amplify its own signaling, I carried out experiments and achieved much stronger induction with very low basal expression compared with conventional systems. The concept was first demonstrated experimentally in transient expression assays and then shown in stable transformant cells after genomic integration. We demonstrated for the first time that artificial positive-feedback regulation could be implemented in gene expression in mammalian cells. This work was among the earliest attempts to treat genes as switches and to investigate their interconnections and feedback loops.

Key References:
• Ko, Takano (1989). A highly inducible system of gene expression by positive feedback production of glucocorticoid receptors.
https://pubmed.ncbi.nlm.nih.gov/2494026/
• Ko et al. (1989). An auto-inducible vector conferring high glucocorticoid-inducibility upon stable transformant cells (1989).
https://pubmed.ncbi.nlm.nih.gov/2558971/


● Stochastic Gene Expression (1990-2012)
I wanted to investigate how the expression of a single gene is regulated at a single cell resolution, as a single mammalian cell contains only two copies of a single gene that are derived from mother and father. I conceived the use of a transgene, beta-galactosidase, whose expression can be visualized by LacZ-staining of cell populations. In this experiment, we discovered for the first time that gene expression is a stochastic process. This body of work is now recognized as foundational and is regarded as the earliest set of papers in the field. For example, Raj and van Oudenaarden wrote in a 2008 Cell review: “One of the first studies to use an expression reporter in single cells to examine the stochastic underpinnings of expression variability was the pioneering work of Ko et al., 1990.”
I also developed a theoretical framework and did a computer simulation of this stochastic gene expression regulation. In this model, transcription factors bind and dissociate randomly from a gene. When a transcription complex is bound (the "on" state), messenger RNA (mRNA) is produced. Without the complex (the "off" state), no transcription occurs and no mRNA production. The increased amount of transcription factors increases the probability of switching from off state to on state, thereby increasing the gene expression levels. Importantly, the model predicted that if the "on" complex was stable, individual cells would exhibit heterogeneous, or variable, levels of gene expression among the cell population. Larson, Singer, and Zenklusen stated in their 2009 Trends in Cell Biology review: “This model of gene induction, sometimes called a Random Telegraph model, was first proposed by Ko (1991).”

Key References:
• Ko, Nakauchi, Takahashi (1990). The dose-dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates.
https://pubmed.ncbi.nlm.nih.gov/2167833/
• Ko (1991). A stochastic model for gene induction.
https://pubmed.ncbi.nlm.nih.gov/1787735/
• Ko (1992). Induction mechanism of a single gene molecule: Stochastic or Deterministic?
https://pubmed.ncbi.nlm.nih.gov/1637366/
• Yang, Ko (2012). Stochastic modeling for the expression of a gene regulated by competing transcription factors.
https://pubmed.ncbi.nlm.nih.gov/22431973/


● Equalized cDNA Libraries (aka Normalized cDNA Libraries) (1990, 1994)
To enable large-scale gene cataloging and global gene expression studies, I began developing a method for constructing equalized cDNA libraries around 1986 and published the paper in 1990. For the first time, this method made it possible to equalize cDNA (gene) clones present at highly variable abundances in standard cDNA libraries. It relied on self-reassociation of short double-stranded cDNAs followed by PCR recovery, which dramatically reduced abundance bias and made rare transcripts (mRNAs) much easier to detect. To identify genes represented in the equalized cDNA libraries, I manually sequenced 184 cDNA clones. This 1990 paper was probably one of the first examples of a large-scale cDNA sequencing project, later known as expressed sequence tag (EST) analysis.
We subsequently applied this method to mouse embryos across development, demonstrating that an equalized library could approximate a broad “whole cDNA catalog” with far less redundancy and improved representation of tissue-specific genes. Interestingly, the highly equalized cDNA library contained only about 15,000 independent genes, close to the current consensus of 20,000–25,000 genes. This was probably among the earliest experimental evidence that mammalian gene sets are smaller than the estimates common at the time (35,000–100,000 genes).

Key References:
• Ko (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs.
https://pubmed.ncbi.nlm.nih.gov/2216762/
• Takahashi, Ko (1994). Towards a whole cDNA catalog: an equalized cDNA library from mouse embryos.
https://pubmed.ncbi.nlm.nih.gov/7829072/


● Mouse Whole Gene Catalog (1990-2003)
After moving to Wayne State University, with the goal of making a mouse whole gene catalog, my lab continued making cDNA libraries from cells and tissues that are otherwise difficult to obtain from human materials. As the automated DNA sequencer became available, we continued sequencing cDNA clones. We also developed a rapid PCR-based gene mapping method utilizing sequence polymorphism commonly found in 3’-UTR of cDNAs (1993, 1994). With the support of NIH grant, we first focused on extraembryonic tissues at peri-implantation stage, generated 3,186 EST, and mapped 155 novel genes in mouse genome (1998). With additional support from ERATO Doi Bioasymmetry Project, we generated cDNA libraries from all the stages of mouse preimplantation embryos (Unfertilized egg, fertilized egg [zygote], 2-cell embryos, 4-cell embryos, 8-cell embryos, Morula, Blastocyst) (2000). We did a large-scale sequencing and generated 25,438 ESTs, representing 9,718 unique genes, and mapped 798 new genes on the mouse genome (2000).
After moving to National Institute on Aging (NIA), National Institutes of Health (NIH), my lab continued making cDNA libraries and sequencing individual cDNA clones. We continued focusing on mouse cells and tissues that are difficult to obtain from humans, such as mouse embryos, newborn ovaries, embryonic stem cells, and tissue stem cells. At the NIA, the project was further expanded. I served as Principal Investigator for NIA mouse cDNA project at the Intramural Research Program, NIA, NIH (1998 – 2004). The project contributed to the research community by sharing the following resources: ~400,000 cDNA sequence information (EST) deposited to the public database (dbEST and GenBank), which is about 10% of total 4,218,080 mouse cDNA sequences in the public database (NCBI/dbEST) at that time with the contribution of the largest number (89,440 out of total 158,039) of mouse cDNA clones/sequences collected from preimplantation embryos at that time; ~0.3 million cDNA clones deposited to the American Type Culture Collection (ATCC); Contribution to the NIH-wide Mammalian Gene Collection (MGC), where 716 (~4%) full-length cDNA clones/genes out of 17,707 (total) were derived from our Mouse cDNA Project at that time.

Key References:
• Takahashi, Ko (1993). The short 3′-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome.
https://pubmed.ncbi.nlm.nih.gov/8486351/
• Ko et al. (1994). Genetic mapping of 40 cDNA clones on the mouse genome by PCR.
https://pubmed.ncbi.nlm.nih.gov/8043949/
• Ko et al. (1998). Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome.
https://pubmed.ncbi.nlm.nih.gov/9811942/
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Piao et al. (2001). Construction of long-transcript enriched cDNA libraries from submicrogram amounts of total RNAs by a universal PCR amplification method.
https://pubmed.ncbi.nlm.nih.gov/11544199/
• Sharov et al. (2003). Transcriptome Analysis of Mouse Stem Cells and Early Embryos.
https://pubmed.ncbi.nlm.nih.gov/14691545/
• Carter et al. (2003). The NIA cDNA Project in mouse stem cells and early embryos.
https://pubmed.ncbi.nlm.nih.gov/14744099/
• Ko (2004). Embryogenomics of preimplantation mammalian development: Current Status.
https://pubmed.ncbi.nlm.nih.gov/14972105/
• Tanaka, Ko (2004). A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst.
https://pubmed.ncbi.nlm.nih.gov/15196723/
• Gerhard et al., (2004). The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
https://pubmed.ncbi.nlm.nih.gov/15489334/


● NIA 15K Mouse cDNA Clone Set (2000) and NIA 7.4K Mouse cDNA Clone Set (2002)
My lab established and publicly distributed the NIA 15K Mouse cDNA Clone Set, which constitutes 15,000 unique mouse genes, and NIA 7.4K Mouse cDNA Clone Set, which constitutes 7,400 additional unique mouse genes. Combined, they cover nearly all mouse genes in the cDNA forms. As public resources, these cDNA clone sets have been freely distributed to more than 11 other NIH institutes and 135 academic centers/research institutions worldwide without any license nor restriction. These cDNA clones have been used to prepare cDNA microarrays for global gene expression profiling.

Key References
• Tanaka et al. (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.
https://pubmed.ncbi.nlm.nih.gov/10922068/
• Kargul et al. (2001). Verification and initial annotation of the NIA mouse 15K cDNA clone set.
https://pubmed.ncbi.nlm.nih.gov/11326268/
• VanBuren et al. (2002). Assembly, verification, and initial annotation of the NIA mouse 7.4K cDNA clone set.
https://pubmed.ncbi.nlm.nih.gov/12466305/


● NIA Mouse Whole cDNA Microarrays (2000)
My lab also made NIA Mouse Whole cDNA Microarrays by spotting 15,000 unique cDNA clones (NIA 15K Mouse cDNA clone set) on nylon membranes (2000). We showed the utility of this microarray for global gene expression profiling of mouse embryonic stem (ES) cells, trophoblast stem (TS) cells, and mouse embryo fibroblast (MEF) cells. We identified distinct molecular signatures of these cell types. We later expanded the coverage of cDNA microarrays by adding NIA 7.4K Mouse cDNA Clone Set, which were distributed to NIA grantees.

Key References
• Tanaka et al. (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.
https://pubmed.ncbi.nlm.nih.gov/10922068/


● Agilent Mouse Whole cDNA Oligonucleotide Microarrays (2003, 2005)
Under a CRADA arrangement with Agilent Technologies, my lab helped the development of the first mouse in situ-synthesized 60-mer oligonucleotide microarrays by designing 60-mer sequences representing all the mouse genes. The mouse 22K development array (containing 22,000 gene features, released in 2003) and the mouse 44K whole genome array (featuring 44,000 gene features, released in 2005) have been commercialized by Agilent Technologies and are widely used globally. The 2003 paper described the global gene expression profiling with as little as 2 ng of total RNA with high reproducibility. This made global expression profiling feasible for extremely small samples such as early embryos and rare stem cell populations. The 2005 paper introduced yeast-derived external RNA spike-in controls, enabling quantitative estimation of absolute transcript abundance, not just relative expression differences. Using this system, my lab showed that mammalian transcriptomes are highly complex, with many genes expressed at very low copy number and many transcripts shared broadly across tissues and stem cell types. My lab also collaborated with Agilent Technologies to develop Rat whole Oligonucleotide Microarrays as part of NIH-wide efforts.

Key References
• Carter et al. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.
https://pubmed.ncbi.nlm.nih.gov/12727912/
• Carter et al (2005). Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.
https://pubmed.ncbi.nlm.nih.gov/15998450/


● Global Gene Expression Patterns in Mouse Preimplantation Embryos (2000, 2004)
My lab provided the first comprehensive views of gene expression across all stages of mouse preimplantation development. In the 2000 study, large-scale EST analysis of stage-specific cDNA libraries identified 25,438 ESTs representing 9,718 genes, revealing that a substantial fraction of the mammalian genome is active during early embryogenesis and that many genes are expressed in a stage-specific, transient manner rather than continuously.
The 2004 study was the first microarray-based global gene expression analysis of mouse preimplantation embryos and further extended the 2000 study, showing coordinated degradation of maternal RNAs and multiple waves of zygotic transcription, including the major zygotic genome activation (ZGA) wave and a second wave, mid-preimplantation gene activation (MGA), preceding compaction and blastocyst formation (2004, 2005). This work was featured in the textbook, “Principles of Development (5th ed.) by Wolpert, Tickle, Arias, Lawrence, Lumsden, Robertson, Meyerowitz, Smith.” Together, these studies revealed the full gene repertoire and wave-like gene activation program underlying early mouse development.
My lab also revealed spatial expression patterns of 91 transcription factors in mouse embryonic blastocysts using whole mount in situ hybridization (2006).

Key References:
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Hamatani et al. (2004). Dynamics of global gene expression changes during mouse preimplantation development.
https://pubmed.ncbi.nlm.nih.gov/14723852/
• Ko (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions.
https://pubmed.ncbi.nlm.nih.gov/15820015/
• Yoshikawa et al. (2006). High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization.
https://pubmed.ncbi.nlm.nih.gov/16325481/


● Half-lives of All mRNAs in Mouse (2009)
My lab provided one of the first genome-scale resources for mRNA stability in mammalian cells by measuring mRNA half-lives for 19,977 mouse genes in embryonic stem cells. It showed that most transcripts are relatively stable, with a median half-life of 7.1 hours, whereas short-lived mRNAs are enriched in regulatory genes such as transcription factors, cell-cycle genes, and developmental regulators. In contrast, stable mRNAs are associated with metabolism, extracellular matrix, cytoskeleton, and protein synthesis. Importantly, the study showed that mRNA stability correlates more strongly with transcript structure than gene function, identifying exon-junction density as a major stabilizing feature and AU-rich, PUF, and CpG-related motifs as destabilizing determinants.

Key Reference:
• Sharova et al. (2009). Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/19001483/


● Bioinformatics Tools (2006-)
My lab developed software tools, databases, and websites for mouse genes and microarray analysis, and made freely available to the research community from our lab server at NIA/NIH. (Most of them are not available at this point, since my lab moved out from NIH.)
• ExAtlas (NIA Array Analysis): statistical analysis of microarray data
• NIA Mouse Gene Index: databases of genes and alternative transcripts
• CisFinder: identification of transcription factor-binding motifs from ChIP-seq data
• CisView: visualization of cis-regulatory modules and transcription factor-binding sites
• Protein Interactions: database of mouse protein interactions transferred from other species

Key References:
• Sharov et al. (2005). A web-based tool for principal component and significance analysis of microarray data.
https://pubmed.ncbi.nlm.nih.gov/15734774/
• Sharov et al. (2005). Genome-wide assembly and analysis of alternative transcripts in mouse.
https://pubmed.ncbi.nlm.nih.gov/15867436/
• Sharov et al. (2006). CisView: a browser and database of cis-regulatory modules predicted in the mouse genome.
https://pubmed.ncbi.nlm.nih.gov/16980320/
• Yellaboina et al. (2008). Prediction of evolutionarily conserved interologs in Mus musculus.
https://pubmed.ncbi.nlm.nih.gov/18842131/
• Sharov, Ko (2009). Exhaustive search for over-represented DNA sequence motifs with CisFinder.
https://pubmed.ncbi.nlm.nih.gov/19740934/
• Sharov et al. (2015). ExAtlas: An interactive online tool for meta-analysis of gene expression data.
https://pubmed.ncbi.nlm.nih.gov/26223199/


● Systematic Manipulation of Transcription Factors in Mouse ES Cells (2009) and Human ES Cells (2020)
To elucidate gene regulatory networks, my lab established a systematic platform to measure the expression changes of all genes caused by manipulating the expression of single transcription factors (TFs) in pluripotent stem cells. In mouse ESCs, inducible overexpression of 50 TFs, followed by a global gene expression profiles by the Agilent Mouse Whole cDNA Microarrays (mentioned above) provided a comprehensive picture of genes regulated by specific TFs and induced the differentiation of mouse ESCs to specific cell/tissue lineages (2009).
We later expanded the number of TF-inducible mouse ESCs to 137 lines (2013) and 185 lines (2016). Complementary shRNA repression revealed striking network robustness: only a few knocked-down factors caused major transcriptomic shifts, mainly along two fate trajectories (2013, 2014). Extending the strategy to human ESCs, 2,135 inducible lines covering 714 genes generated large-scale morphological and transcriptomic maps, classifying factors that drive distinct human differentiation programs across multiple developmental lineages (2020).

Key Resources:
• NIA Transcription factor (TF)-manipulable Mouse ES Cell Bank: 103 TF-manipulable mouse ES cell lines have been made available from Coriell Institute for Medical Research, https://www.coriell.org/0/Sections/Collections/NIA/Mesc.aspx?PgId=691&coll=AG
• Keio Transcription factor (TF)-manipulable Human ES Cell Bank: Cell Lines of TF-manipulated human ES cells: Deposited and available from RIKEN Bioresource Center Cell Bank (search “Minoru Ko” at https://cell.brc.riken.jp/en/ ). Total 2142 cell lines.
• Database for Transcription Factor (TF)-manipulated human ES cell data (linked from the paper) (http://www.systemsmedicine.jp/crest/plasmid/ ).
• Plasmid vectors for mammalian gene expression: Deposited and available from Addgene (search “Minoru Ko” in https://www.addgene.org/ ). Total 43 plasmids.

Key References
• Matoba et al. (2006). Dissecting oct3/4-regulated gene networks in embryonic stem cells by expression profiling.
https://pubmed.ncbi.nlm.nih.gov/17183653/
• Nishiyama et al. (2009). Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/19796622/
• Correa-Cerro et al. (2011). Generation of mouse ES cell lines engineered for the forced induction of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/22355682/
• Nishiyama et al. (2013). Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells.
https://pubmed.ncbi.nlm.nih.gov/23462645/
• Sharov et al., (2014). Chromatin properties of regulatory DNA probed by manipulation of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/24918633/
• Yamamizu et al. (2016). Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines.
https://pubmed.ncbi.nlm.nih.gov/27150017/
• Nakatake et al. (2020). Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors.
https://pubmed.ncbi.nlm.nih.gov/32433964/


● Transcription Factor mRNA-based Human ES/iPS Cell Differentiation (2013-2020)
My lab has pioneered the use of a correlation matrix of global gene expression from systematic manipulation of transcription factors described above and developed a systematic method to identify transcription factors that rapidly direct embryonic stem cells into specific cell lineages.
My lab has also pioneered the use of synthetic messenger RNAs (syn‑mRNAs) to program pluripotent stem cells into defined lineages. In mouse ES cells we showed that transient over‑expression of single master regulators (e.g., Myod1, Hnf4a, Sfpi1, Ascl1) directly induced differentiation of mouse ESCs into myocytes, hepatocytes, blood cells, and neurons (2013).
By combining epigenetic priming (using mRNA encoding JMJD3c) with mRNA encoding MYOD1 we dramatically increased myogenic conversion of human ESCs/iPSCs (2016, 2017a, 2018a). A systematic TF‑correlation matrix identified lineage‑specific TFs that efficiently drive human ESC/iPSC differentiation to lacrimal‑gland epithelium (2017b), pancreatic endocrine cells (2018b), kidney organoids (2019), and dopaminergic neurons (2020). Synthetic mRNA cocktails (e.g., NGN1, NGN2, NGN3, ND1, ND2) also enable rapid (≤10 days) generation of functional neurons (2017c). Notably, we also showed that NGN3 alone is a potent neural inducer (2017d). Together, these studies establish a versatile, footprint‑free platform for fast, scalable, and clinically relevant cell‑type specification.

Key References:
• Yamamizu et al. (2013). Identification of transcription factors for lineage-specific ESC differentiation.
https://pubmed.ncbi.nlm.nih.gov/24371809/
• Akiyama et al. (2016). Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/27802135/
• Akiyama et al. (2017a). Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells.
https://pubmed.ncbi.nlm.nih.gov/28491098/
• Hirayama et al. (2017b). Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells.
https://pubmed.ncbi.nlm.nih.gov/28649419/
• Goparaju et al. (2017c). Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/28205555/
• Matsushita et al. (2017d). Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors.
https://pubmed.ncbi.nlm.nih.gov/28610919/
• Akiyama et al. (2018a). Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing.
https://pubmed.ncbi.nlm.nih.gov/29352121/
• Ida et al. (2018b). Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/30359326/
• Hiratsuka et al. (2019). Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/30696889/
• Akiyama et al. (2020). Synthetic mRNA-based differentiation method enables early detection of Parkinson’s phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/33342090/


● Controllable self-replicating RNA (c-srRNA) vectors as T-cell vaccines (2022-)
My lab developed a temperature‑controlled self‑replicating RNA (c‑srRNA) vectors and used it for a vaccine delivered intradermally without lipid nanoparticles (2023a). Optimized to replicate at skin temperature (30‑35°C) and inactivate at core body temperature (37°C), it induced CD4⁺ and CD8⁺ T‑cell responses while producing little antibody unless followed by protein boost. Thus, this vaccine functions as a T-cell vaccine, which can potentially be used as a vaccine against broad spectrum of variant pathogens.
We developed a c-srRNA vector encoding the RBD of SARS-CoV-2 (EXG-5003) and used it for a double‑blind, placebo‑controlled phase I/II trial in healthy adults (2023b). The vaccine was safe, elicited cellular immunity and no humoral response alone, but primed enhanced T‑cell and antibody responses after subsequent approved mRNA vaccination (2023b).

Key References:
• Amano et al. (2023a). Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity.
https://pubmed.ncbi.nlm.nih.gov/36968065/
• Koseki et al. (2023b). A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2.
https://pubmed.ncbi.nlm.nih.gov/38140172/


● ZSCAN4 Discovery and Characterizations (2007-)
This work originated from the Mouse Whole Gene Catalog project that we began in the early 1990s and was based on comprehensive gene-expression profiles of early embryos, the reproductive system, and stem cells (2000, 2003, 2004). We searched for genes that are specifically and transiently expressed during zygotic genome activation and identified Zscan4 as a gene specifically expressed in mouse two-cell-stage embryos in the early 2000s (2007a). When we examined the expression pattern of Zscan4 in mouse ES cells by whole-mount mRNA in situ hybridization, we found that Zscan4 is highly expressed, but only in 1–5% of cells at any given moment (2007a, 2007b). This surprising result was reminiscent of the gene-expression pattern I had studied in “stochastic gene expression.” This prompted us to investigate Zscan4 further, although we later found that Zscan4 expression was not a stochastic event. We found that Zscan4 plays a key role in telomere elongation (2010), genome stability (2010), karyotype stability (2015a), DNA methylation (2015b), and epigenome regulation (2015b). Based on these basic science studies about ZSCAN4, our team at Elixirgen Therapeutics developed EXG34217, a cell and gene therapy for Telomere Biology Disorders (TBDs) with bone marrow failure (https://clinicaltrials.gov/study/NCT04211714). Early results were published in NEJM Evidence (2025).

• ZSCAN4 is a mammalian-specific gene encoding one SCAN domain and four zinc finger domains (2007a).
• In mice, ZSCAN4 expression is restricted to the two-cell stage of preimplantation embryos. Either suppression or prolongation of this transient expression results in developmental arrest and abnormalities (2007a).
• In mouse ES cells, ZSCAN4 expression is transient, lasting only a few hours. At any given time, only 1–5% of undifferentiated ES cells are ZSCAN4-positive (2007a). Nevertheless, after approximately nine passages, nearly all cells have cycled through a ZSCAN4+ state (2010).
• Entry into the ZSCAN4+ state triggers multiple transient phenomena: rapid telomere elongation via homologous recombination, induction of two-cell-stage-specific genes, temporary global repression of protein synthesis, and activation of meiosis-specific genes (2010).
• When ES cells are prevented from entering the ZSCAN4+ state, they progressively lose proliferative capacity after approximately six passages and ultimately undergo culture crisis. At this stage, most cells exhibit abnormal karyotypes, indicating that transient ZSCAN4 activation is essential for genomic stability (2010).
• Forced, transient induction of exogenous ZSCAN4 enables ES cells to be maintained in culture far longer than usual without any loss of quality, suggesting that regulated ZSCAN4 expression can both preserve and rejuvenate stem-cell function (2013a).
• Incorporating ZSCAN4 during induced pluripotent stem (iPS) cell generation markedly improves iPS-cell quality (2012).
• In the human pancreas, ZSCAN4 is strongly expressed in a small population of putative stem cells, suggesting conserved roles beyond murine models (2013c).
• Forced expression of the ZSCAN4 gene suggested the possibility of repairing chromosomal abnormalities in mouse ES cells, primary fibroblasts from Down syndrome patients, and primary fibroblasts from Edwards syndrome patients (2015a).
• We have also shown that, when ZSCAN4 is expressed in mouse ES cells, a transient and dynamic change occurs in the epigenome; chromatin—particularly heterochromatin—undergoes de-repression and re-repression; RNAs from telomeres, pericentromeres, and other regions become transiently expressed; and a phenomenon in which heterochromatin condenses around nucleoli is also observed (2015b, 2024).
• In mice of both sexes, Zscan4 was found to be specifically expressed during meiosis. No gene had previously been reported to be expressed specifically in the pachytene and diplotene stages of the first meiotic division; Zscan4 therefore represents the first such example (2016c).
• Because Zscan4 is not normally expressed but appears only intermittently, the maintenance of genome stability and telomere elongation are not continuous processes but occur sporadically, suggesting a highly unique “cellular rejuvenation” function.
• We conducted a first-in-human phase I/II study of EXG34217, an autologous CD34+ hematopoietic stem cell product transiently exposed ex vivo to a temperature-sensitive Sendai virus vector encoding ZSCAN4, for patients with telomere biology disorders with bone marrow failure. Two underwent successful mobilization, apheresis, and infusion. In both treated patients, telomere elongation was observed ex vivo and longer-telomere hematopoietic cell populations later appeared in vivo. Neutrophil counts improved, and one patient no longer required intermittent G-CSF. No acute safety problems followed infusion (2025).

Key References:
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Carter et al. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.
https://pubmed.ncbi.nlm.nih.gov/12727912/
• Hamatani et al. (2004). Dynamics of global gene expression changes during mouse preimplantation development.
https://pubmed.ncbi.nlm.nih.gov/14723852/
• Falco et al. (2007a). Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/17553482/
• Carter et al. (2007b). An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells.
https://pubmed.ncbi.nlm.nih.gov/18178135/
• Zalzman et al. (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells.
https://pubmed.ncbi.nlm.nih.gov/20336070/
• Hirata et al. (2012). Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/22355722/
• Amano et al. (2013a). Zscan4 restores the developmental potency of embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/23739662/
• Hung et al. (2013b). Repression of global protein synthesis by eif1a-like genes that are expressed specifically in the two-cell embryos and the transient zscan4-positive state of embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/23649898/
• Ko et al. (2013c). Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas.
https://pubmed.ncbi.nlm.nih.gov/23599043/
• Amano et al. (2015a). Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures.
https://pubmed.ncbi.nlm.nih.gov/26324424/
• Akiyama et al. (2015b). Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/26324425/
• Ko (2016a). Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4.
https://pubmed.ncbi.nlm.nih.gov/27475850/
• Sharova et al. (2016b). Emergence of undifferentiated colonies from mouse embryonic stem cells undergoing differentiation by retinoic acid treatment.
https://pubmed.ncbi.nlm.nih.gov/27130680/
• Ishiguro et al. (2016c). Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis.
https://pubmed.ncbi.nlm.nih.gov/27699653/
• Ishiguro et al. (2016d) Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos.
https://pubmed.ncbi.nlm.nih.gov/27699651/
• Akiyama et al. (2024). ZSCAN4-binding motif-TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes.
https://pubmed.ncbi.nlm.nih.gov/38153767/
• Myers et al. (2025). Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.
https://pubmed.ncbi.nlm.nih.gov/39998303/




■ FULL BIOGRAPHY OF Minoru S.H. Ko, M.D., Ph.D.

● CURRENT POSITION
• Chief Scientific Officer, Elixirgen Therapeutics, Inc.
• Professor Emeritus, Keio University


● EDUCATION
• Keio University School of Medicine, Tokyo, Japan (M.D., 1986)
• Keio University School of Medicine, Tokyo, Japan (Ph.D., 1991; Advisor Dr. Toshiya Takano)


● PROFESSIONAL APPOINTMENTS
1988-1991 Researcher, Furusawa MorphoGene Project, ERATO, JST, Tsukuba, Japan

1991-1992 Group Leader, Furusawa MorphoGene Project, ERATO, JST, Tsukuba, Japan

1992-1996 Assistant Professor, Center for Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, Michigan

1996-1998 Associate Professor (Tenured), Center for Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, Michigan

1998-2011 Senior Investigator (Tenured), Chief of Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland

2012–2016 Special Volunteer, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland

2012- Co-founder and Chief Scientific Officer, Elixirgen, LLC, Baltimore, Maryland

2012-2022 Professor and Chair, Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan

2016-2025 Founder and Chief Scientific Officer, Elixirgen Scientific, Inc. (now Ricoh Biosciences, Inc.), Baltimore, Maryland

2017- Co-founder and Chief Scientific Officer, Elixirgen Therapeutics, Inc., Baltimore, Maryland

2022- Professor Emeritus, Keio University School of Medicine, Tokyo, Japan


● OTHER PROFESSIONAL APPOINTMENTS

1988-1992 Adjunct Instructor, Department of Microbiology, Keio University School of Medicine, Tokyo, Japan

1996-1998 Group Leader, Genome Asymmetry Group, ERATO Doi Bioasymmetry Project, JST, at Wayne State University School of Medicine, Detroit, MI

1999-2004 Project Officer, DNA sequencing contract to PE-Applied Biosystems: mouse cDNA project, NIH

1998-2007 Project Officer, UNISYS Informatics Support for large-scale sequencing project, NIH

2001-2008 Principal Investigator, CRADA with Agilent Technologies: Design and development of mouse DNA microarrays, NIH

2004-2011 Co-leader, NIH Stem Cell Interest Group

2012-2016 Special Volunteer, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD

2013–2015 Research Leader, MEXT Center of Innovation Program (COI-STREAM) trial, “Center for System Medicine to Create the Global Standard for Healthy Longevity” at Keio University, Tokyo, Japan

2013–2015 Vice Dean, Keio University School of Medicine, Tokyo, Japan

2015-2015 Director, Centenarian Research Center, Keio University School of Medicine

2015–2017 Director, Keio University Leading Research Center for System Medicine Research and Development

2017–2021 Director, Keio University Leading Research Center for Medical AI


● HONORS AND AWARDS
2001 NIH Merit Award
2009 NIA Director’s Award
2011 NIH Director’s Award


● LICENSURE AND BOARD CERTIFICATION
National License for Medical Practice, Japan, 1986


● STUDY SECTIONS/REVIEW COMMITTEES (EXAMPLES)
1993 Department of Energy (DOE) Review Panel on US Human Genome Program

1996 National Science Foundation (NSF) Review Panel for the RFA on Human Genome Diversity

1997 National Institutes of Health (NIH) Genome Study Section

1999 National Institutes of Health (NIH) Genome Study Section

1999 Department of Energy (DOE) Review Panel on US Human Genome Program

2000 National Institute on Aging (NIH), Review Panel for the High Throughput Technology Supplemental Requests

2004 Review Panel for the research program of Oakridge National Laboratory, DOE

2004 Review Panel for the grant proposal to Navy Research Program, DOD

2004 Reviewer for a grant proposal to March of Dimes Birth Defects Foundation.

2004 Reviewer, NSF CAREER Proposal

2004 Reviewer, NIH JSPS Fellowship Review Committee

2005 Reviewer, NIH JSPS Fellowship Review Committee

2005 Reviewer, NSF Grant Proposal

2005 Reviewer, NSF Grant Proposal

2006 Reviewer, NSF Grant Proposal

2006 Reviewer, NIH Graduate Students Festivals

2007 Reviewer, NIH JSPS Fellowship Review Committee

2007 Reviewer, NSF CAREER Proposal

2008 Reviewer, NIH JSPS Fellowship Review Committee

(Omitted after 2008))


● ADVISORY BOARDS (EXAMPLES)
1994 Member, Advisory Board, Experimental Evolution Workshop, ERATO, JST, Tokyo, Japan.

1995 Member, National Science Foundation (NSF) Advisory Panel on Human Genome Diversity

2005 Scientific Advisory Board for Bovine Embryo Transcriptome Analysis (BETA) Project,
Canadian Genome Initiative, Canada (Invited, but declined due to NIH regulation)

2005-2008 Advisory Board, The Jackson Laboratory, Mouse Genome Database (MGD), USA

2006-2009 Advisory Board, The Jackson Laboratory, Gene Expression Database (GXD), USA

2006 Discussant, Round table discussion on Developmental Biology and Stem Cells,
Nature Publishing Group

2014–2018 Special Advisor (Member, Research Strategy Council, Office of the President), RIKEN, Japan

2014– Member, Research Advisory Committee, Central Institute for Experimental Animals (CIEA), now called Central Institute for Experimental Medicine and Life Sciences (CIEM), Kawasaki, Japan

2017–2019 Member, External Expert Committee, RIKEN Program for Promotion of the Medical Science Innovation Hub


● GRANT PROPOSAL REVIEW (EXAMPLES)
2007 Wellcome Trust Grant Review: Stem Cell Biology

2007 Canada Research Chair Review: Stem Cell Biology

2007 AFM Research Grant Review: Stem Cell Biology

(Omitted after 2008)


● SESSION CHAIR (EXAMPLES)
2001 Co-Chair, NH Research Festival, Minisymposium “Mouse Embryogenomics: Frontiers of Developmental Biology and Genomics”


● LABORATORY MEMBERS AT WAYNE STATE UNIVERSITY, DETROIT, MICHIGAN (1992-1998)

Postdoctoral Fellows
1993-1993 Satoshi Matsuda, M.D./Ph.D.
1993-1993 Shigeru Masamura, M.D./Ph.D.
1994-1994 Nanding Zhao, Ph.D.
1995-1996 Yushun Cui, Ph.D.
1995-1997 Shinichi Yotsumoto, M.D./Ph.D.
1995-1997 Hiroyuki Fujiwara, Ph.D.
1995-1997 Hiroshi Nakashima, M.D./Ph.D.
1995-1997 Hiroshi Harada, M.D.
1996-1997 Wei Xue, M.D./Ph.D.
1996-1998 John Kitchen, Ph.D.
1997-1998 Tokihiko Shimada, M.D./Ph.D.
1996-1998 Rhonda H. Nicholson, Ph.D.

Research Assistant/Technical Staff
1992-1995 Joseph H. Horton, B.S.
1992-1997 Xueqian Wang, M.D.
1995-1995 Cheryl Moore, B.S.
1995-1995 Rene Salyer, B.S.
1995-1995 Ted Scancella, B.S.
1995-1996 Eric Pryor, B.S.
1995-1996 Jason Paris, B.S.
1995-1997 Jeannine Wells-Smith, B.S.
1995-1998 Tracy A. Threat, B.S.
1995-1998 Xiaohong Wang, M.S.
1996-1997 Shiho Fukui, B.A.
1996-1998 Sonja Davis, B.P.A.
1997-1998 Tong Sun, M.S.
1997-1998 Erico Yogo, B.A.
1997-1998 Yuling Liang, B.S.
1996-1997 Scott P. Mason, B.S.
1996-1998 Meng K. Lim, B.S.
1996-1998 Marija J. Grahovac, B.S.
1996-1997 Maged K. Rizk, B.S.
1997-1997 Paul Paonessa, B.S.
1995-1996 Jason Yoas, B.S.
1996-1997 Sundip S. Patel, B.S.

Student Assistant (IT Computational work)
1993-1994 Srinivas Inaganti, B.S.
1994-1995 Ramachandra Kakulawaram, B.S.
1994-1995 Sridhar Reddy Andapally, B.S.
1995-1996 Jeevan Nalamada, B.S.
1995-1996 Rajiv Muthyala, B.S.
1996-1997 Sunil Kosuru, B.S.
1996-1997 Sudheer Tummula, B.S.

Graduate Student, Rotation
1994 Michail Kolonin, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine
1994 Chongsuk Ryou, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine
1994 Kirk Yousif, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine
1996 Sompong Vongpunsawad, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine

High School Student Intern
1993-1994 Jing Qian, Cass Tech High School.
1994-1995 Carla Ellison, Cass Tech High School.
1995-1996 Dia Hodnett, Cass Tech High School.


● LABORATORY MEMBERS AT NIA, NIH, BALTIMORE, MARYLAND (1998-2011)

Staff Scientist, Biologists, and Technical Staff
2003-2011 Alexei A. Sharov, Ph.D.
2003-2011 Lioudmila Sharova, Ph.D.
2009-2011 Misa Amano, M.S.
2009-2011 Hong Yu, B.S.
1998-2011 Yulan Piao, M.D.
1999-2011 Carole Stagg, B.S.
2002-2010 Uwem Bassey, B.S.
2005-2006 Eric Douglas
1998-2000 Meng K. Lim, M.S.
1999-1999 Tammy Stockette, M.S.
1999-2001 Amber Luo, M.D.
2000-2002 Shirley Deng, M.S.
2001-2004 Patrick Martin, B.S.
2003-2005 Yuxia Wang, B.S.

Computer Specialists
1999-2011 Dawood Dudekula, B.S.
1999-2011 Yong Qian, M.S.

Postdoctoral Fellows
2010-2011 Tomohiko Akiyama, Ph.D.
2008-2011 Hsih-Te Yang, Ph.D.
2011-2011 Sandy Hung, Ph.D.
2011-2011 Raymond Wong, Ph.D.
2008-2011 Yuhki Nakatake, Ph.D.
2009-2011 Tomokazu Amano, Ph.D.
2007-2011 Michal Zalzman, Ph.D.
2009-2011 Tetsuya Hirata, M.D., Ph.D.
2008-2010 Akira Nishiyama, Ph.D.
2008-2011 Li Xin, M.D., Ph.D.
2009-2011 Lina S. Correa-Cerro, M.D., Ph.D.
2009-2010 Manxiang Li, Ph.D.
2007-2010 Manuela Monti, Ph.D.
2005- 2008 Ilaria Stanghellini, Ph.D.
2005-2005 Wakako Hashimoto, M.D.
2003-2006 Ryo Matoba, Ph.D.
2004-2007 Sung-Lim Lee, D.V.M., Ph.D.
2002-2006 Vincent VanBuren, Ph.D.
2002-2007 Geppino Falco, Ph.D.
2000-2006 Wendy L. Kimber, Ph.D.
2000-2006 Mark G. Carter, Ph.D.
2000-2006 Kazuhiro Aiba, Ph.D.
2001-2004 Toshiyuki Yoshikawa, M.D., Ph.D.
2001-2004 Toshio Hamatani, M.D., Ph.D.
2001-2001 Hiroshi Suemizu, Ph.D.
2000-2000 Maria Granovsky, Ph.D.
1998-2000 Serafino Pantano, Ph.D.
1998-2000 Yuri Sano, M.D., Ph.D.
1998-2003 Tetsuya Tanaka, Ph.D.
1999-2002 Saied Jaradat, Ph.D.

Post baccalaureate Fellows
1998-1999 Marija J. Grahovac, M.S.
1998-2001 George Kargul, M.S.
2008-2009 Marshall Thomas
2008-2009 Gregory Mowrer
2008-2009 Emily Meyers
2008-2009 Samir Mehta
2008-2009 Sarah Yee
2009-2011 Hien Hoang
2009-2009 Eugene Kim
2009-2010 Richard Tapnio
2009-2011 Bernard Y. Binder
2010-2011 Justin Malinou
2010-2011 Sarah Sheer
2010-2011 Jean S. Cadet

Summer Students:
1999 Anastasia Kolendo
2000 Roman Johnson
2001 Brian Everist
2002 Lawrence David
2002, 2003 Arpun Nagaraja
2003 Lauren Wilson
2003, 2004 Ajish George
2005 Tara Howard

Visiting Students:
2004 Maud Vallee, Ph.D. candidate
2005 Nina Rogers, Ph.D. candidate


● LABORATORY MEMBERS AT DEPARTMENT OF SYSTEMS MEDICINE, KEIO UNIVERSITY SCHOOL OF MEDICINE, TOKYO (2012-2022)

2012-2022 Shigeru Ko, M.D., Ph.D. (Associate Professor/Project Professor)
2012-2020 Yuki Nakatake, Ph.D. (Assistant Professor)
2012-2019 Nana Chikazawa, M.S. (Project Researcher)
2012-2018 Mayumi Oda, Ph.D. (Assistant Professor)
2012-2022 Norio Goda, Ph.D. (Project Assistant Professor)
2012-2012 Go Nagamatsu, Ph.D. (Assistant Professor)
2012-2012 Yuko Isono (Office Manager)
2012-2015 Masatoshi Hirayama, M.D. (Visiting Ph.D. Graduate Student)
2012-2014 Tomoo Ueno (Technical Staff)
2012-2014 Emi Tsutsui (Office Manager)
2012-2016 Miki Sakota (Project Researcher)
2012-2014 Naoko Fujita (Technical Staff)
2013-2018 Shunichi Wakabayashi (Project Researcher)
2013-2022 Tomohiko Akiyama, Ph.D. (Assistant Professor)
2013-2021 Saeko Sato (Project Researcher)
2013-2014 Kenta Tsutsui, M.D., Ph.D. (Collaborative Researcher)
2013-2016 Atsushi Hiroike, Ph.D. (Project Lecturer)
2013-2014 Naoto Akira (Collaborative Researcher)
2013-2015 Lars Martin Jakt, Ph. D. (Project Lecturer)
2013-2015 Siu Shan Mak, Ph.D. (Project Assistant Professor)
2013-2016 Miyako Murakami (Project Researcher)
2013-2015 Shih Te Yang, Ph.D. (Visiting Assistant Professor)
2013-2015 Fumi Higashimura (Office Manager)
2013-2018 Sravan Kumar Goparaju, Ph.D. (Project Assistant Professor)
2013-2014 Kara Besher (Office Manager)
2013-2014 Maiko Mori (Office Manager)
2014-2018 Ken Hiratsuka, M.D. (Visiting Ph.D. Graduate Student)
2014-2018 Misako Matsushita, M.D. (Visiting Ph.D. Graduate Student)
2014-2022 Yoko Tauchi (Office Manager)
2014-2019 Mayumi Ikeda (Office Manager)
2014-2016 Ayano Murase (Office Manager)
2014-2019 Hiromi Kimura (Project Researcher)
2014-2019 Kei-ichiro Ishiguro, Ph.D. (Project Associate Professor)
2014-2016 Atsumi Soma, Ph.D. (Project Faculty)
2014-2016 Chiaki Okura (Project Researcher)
2014-2016 Ryo Matoba, Ph.D. (Project Lecturer)
2015-2015 Yuki Aoki, M.D. (Collaborative Researcher)
2015-2017 Hideomi Ida, M.D. (Collaborative Researcher)
2015-2017 Yann Tapponier, Ph.D. (Postdoc Fellow)
2015-2015 Jun Tanigawa, Ph.D. (Collaborative Researcher)
2016-2016 Kazuto Katsuse, M.D. (Ph.D. Graduate Student)
2016-2018 Hanaka Saito (MS Graduate Student)
2020-2022 Toshiya Nakahara (MS Graduate Student)


● PRESENTATIONS (examples)

Invited international or national meetings
1992 Taniguchi International Symposium entitled "cDNA Research Today," Osaka, Japan. Towards a mouse whole cDNA catalog.

1992 Winter Conference of Korean Association of Molecular Biology, Suanbo, Republic Korea. Towards a mouse whole cDNA catalog.

1992 The 7th Molossinus Symposium, Takasaki, Japan. Mouse whole cDNA catalog and its application for gene mapping.

1992 2nd International Workshop on the identification of Transcribed Sequences, San Francisco. The 3'-end region of cDNAs as PCR-based polymorphic markers for an expression map of the mouse genome.

1995 Human Gene Map Workshop II, Banbury Center, Cold Spring Harbor Laboratory

1995 Panelist, Panel discussion for the mouse EST project, The 9th International Mouse Genome Conference, Ann Arbor, Michigan

1996 The 4th JRDC International Symposium, Experimental Approaches to the Evolutionary Biology, Tokyo, Japan

1997 The Tenth International Workshop organized by the International Institute of Genetics and Biophysics, CNR Naples, Italy. Title: Genome-based analysis of gene regulation and its evolution”

1999 The Jackson Laboratory Symposium (June 30- July 3, 1999), "Mouse Initiatives: Advanced Functional Genomics," Bar Harbor, Maine, USA. Developmental Genomic Approach to Mouse Embryology.

2000 International Symposium “Topics from Human Genome Project” (January 17-January 18, 2000), Tokyo, Japan. Developmental Genomic Approach to Mouse Embryology.

2000 ERATO Doi Bioasymmetry Project Symposium (September 6, 2000), Makuhari, Chiba, Japan.

2000 The 3rd International Workshop on Advanced Genomics (Nov 13 - 14, 2000), Yokohama, Japan.

2001 Schering Minisymposium “Molecular Mechanisms of Implantation”, Berlin, Germany. February 2nd , 2001.

2001 Keystone Symposium “Pluripotent Stem Cells: Biology and Applications (C1)” Durango, Colorado. Feb 6 - Feb 11, 2001.

2001 The Sixth Annual Mayo-Luther Forum on Hematopoietic Stem Cells, Mayo Clinic, Rochester, Minnesota, June 15, 2001.

2001 NIH Research Festival, Minisymposium “Mouse Embryogenomics: Frontiers of Developmental Biology and Genomics,” Maryland, October 3, 2001.

2001 International Symposium on Stem Cells and Therapeutic Cloning, Seoul, Korea. November 25, 2001.

2002 The 2nd International Symposium: Frontiers in Pancreatic Research, Nagoya, Japan. March 30-April 1.

2002 International Workshop on embryo genomics in farm animals. July 19 (In conjunction with the American Association of Animal Science Meeting July 21-24), Quebec, Canada.

2002 Serono Symposia International conference on “Genesis and Fate of the Preimplantation Embryo”, September 29-October 1, 2002 in Sorrento, Italy.

2003 Human Genome Meeting (HGM) 2003, Plenary Session on, 'Stem Cell Genomics', Cancun, Mexico, April 27-30, 2003.

2003 Serono Foundation, Workshop on Human Implantation Devoted to Genomics/Proteomics Discovery of The Reproductive Tract In Health And Disease. Madrid, Spain, June 28, 2003.

2004 International Embryo Transfer Society Annual Conference, Portland, Oregon, USA, January 11-13.

2004 Society for Gynecologic Investigation, Annual Meeting, Houston, Texas, March, 2004.

2004 PRICPS2004, the 1st Pacific-Rim International Conference on Protein Science, Yokohama, Japan, April 14-18,2004.

2004 Gordon Research Conference on Reproductive Tract Biology. Connecticut College in New London, Connecticut. June 6-11, 2004.

2004 Cold Spring Harbor Laboratory Course. Molecular Embryology of the Mouse. June 9-29, 2004. Lecture on Microarrays and Early Development.

2004 International Symposium at The Royal Society 6-9 Carlton House Terrace, London, SW1Y 5AG, September 30 – October 1, 2004: MORAL, LEGAL, AND SOCIAL IMPLICATIONS OF REPRODUCTIVE TECHNOLOGY.

2004 S.I.S.M.E.R. forum: Genesis of Life, Bologna, Italy. Sep 11, 2004.

2005 The Sixth International Symposium on Preimplantation Genetics. Queen Elizabeth II Conference Centre, London, UK: 19-22 May 2005.

2005 International Stem Cell Symposium, Kyoto, Japan, November.

2005 The 2nd Annual Meeting for the Korean Society of Animal Reproduction. Oct 26-27, Seoul, Korea (Invited, but declined due to schedule conflict)

2006 2nd International Symposium on Animal Functional Genomics (2nd ISAFG) on May 16-19, 2006. Michigan State University, East Lansing, Michigan, USA (Invited, but declined due to NIH regulation).

2006 "New Insights and Perspectives in Stem Cell Research", International Symposium to cerebrate 100th year of Camillo Golgi’s Nobel Prize. University of Pavia, Pavia, Italy. May 16th - 17th, 2006.

2006 Tecnobios Procreazione Symposium 2006 and 2nd International Conference on the Cryopreservation of the Human Oocyte. Bologna, Italy. October 5-7, 2006.

2006 6th International Symposium on Developmental Biotechnology, October 27, 2006. Seoul, South Korea.

2006 16th Lake Shirakaba Conference, The Caribbean Islands, Grenada, December 6-7, 2006. Invited, but declined due to the schedule conflict.

2007 The fifth annual CDB Symposium "Germ Line versus Soma: Towards Generating Totipotency", RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. March 26-28, 2007.

2007 34th Annual National Conference of the Association of Clinical Biochemists of India, Delhi, India, 18th-20th December, 2007. Invited, but declined due to the schedule conflict.

2007 Reproductive Biology Course, Woods Hole Marine Biological Laboratory, MA
2007 40th Annual Meeting of the Society for the Study of Reproduction, San Antonio, Texas, July 22-25.

2007 17th Lake Shirakaba Conference, Vedbaek, Denmark, October 29-31.
2007 Symposium on Germ Cell Development, Reprogramming, and Epigenetics Tokyo, Japan. November 21 and 22.

2008 Stem Cell Symposium (Memorial Symposium for late Anne McLaren). Pavia, Italy, January 2008. Invited, but declined due to the conflict of schedule.

2008 Mini symposium for Preimplantation Development, Temple University, PA. August 15-16. Invited, but declined due to the conflict of schedule.

2008 Reproductive Biology Course, Woods Hole Marine Biological Laboratory, MA

2009 Pre-congress Course entitled "From Gamete to Heartbeat: the missing link" at the 2009 ESHRE Annual Meeting in Amsterdam, 28 June 2009. Invited, but declined due to the conflict of schedule.

2009 Keystone Symposium Preimplantation Embryos, invited, but declined due to the conflict of schedule.

2009 NIH Research Festival, Stem Cell Biology, Bethesda, MD.

2009 Plenary Lecture, Japanese Ova Society, Tokyo, Japan.

2009 Systems Biology of Human Aging Symposium, Baltimore, MD.

2010 Systems Biology of Stem Cells, UC, Irvine, invited, but declined due to the conflict of schedule.

2010 Abreu Memorial Keynote Address at the National Student Research Forum (NSRF). University of Texas Medical Branch, Galveston, TX, invited, but declined due to the conflict of schedule

2010 JSPS/JHU/NIA Symposium Aging vs. Regenerative Medicine: How Much Can Stem Cells Do? Baltimore, MD

2011 Scottish Stem Cell Network Symposium, “Mechanisms of Lineage Specification,” Edinburgh, UK

2011 BIO 2011 Convention, Washington, D.C.

2011 The ninth annual CDB Symposium "Epigenetic Landscape in Development and Disease", RIKEN Center for Developmental Biology (CDB) in Kobe, Japan.

2011 KEY Forum in Developmental Biology and Regenerative Medicine, Kumamoto University, Kumamoto, Japan

2011 SENS Foundation 5th Symposium, Queens’ College, Cambridge, UK

2011 Serono Symposia International Foundation Conference on: Individualized controlled ovarian stimulation and objective gametes and embryo selection, Yokohama, Japan

2012 How do ES cells maintain their exceptional genome stability? Baltimore Area Repair Symposium (BARS), Baltimore, Maryland, USA

2012 Recapitulating embryonic program: Reactivation of early embryonic genes by Zscan4 during the generation of iPSCs. Invited lecture. 11th Congress of the Japanese Society for Regenerative Medicine, Yokohama, Japan.

2012 What ES cells can teach us about immortality and rejuvenation. Symposium, Japanese Society of Anti-Aging Medicine, Tokyo, Japan.

2013 Mechanisms for maintaining genome stability in embryonic stem cells. Annual Meeting of the Epigenome Research Society, Nara, Japan.

2013 Current status and future prospects of systems medicine. Toward the Realization of Personalized Medicine—Perspectives from companion diagnostics, preventive medicine, and systems medicine. BioJapan 2013 Symposium, Yokohama, Japan.

2013 How do ES cells maintain their exceptional genome stability? NIEHS Symposium on Unlocking the Promise of Stem Cells. National Institute of Environmental Health Sciences, National Institutes of Health. Durham, North Carolina, USA.

2013 Cellular aging and rejuvenation learned from stem cells. 6th Forum, International Medical Science Research Society, Tokyo, Japan.

2013 Stem cell gene networks. Osaka University Symposium on Mathematical Sciences, Osaka, Japan.

2013 Mechanisms for maintaining genome stability in embryonic stem cells. Symposium, Annual Meeting of the Molecular Biology Society of Japan, Kobe, Japan.

2013 Stem cell gene networks. Annual Meeting of the Japan Society for Industrial and Applied Mathematics, Fukuoka, Japan.

2013 Controlling cell differentiation through understanding gene regulatory networks. Symposium, “Current Status of Developmental and Regenerative Research Using Systems Biology Approaches,” 86th Annual Meeting of the Japanese Biochemical Society, Yokohama, Japan.

2014 Preimplantation embryos and systems medicine. 32nd Annual Meeting of the Japan Society of Fertilization and Implantation. Invited lecture. Tokyo, Japan.

2015 Systematic Analyses of Transcription Factor Networks in Mouse and Human Pluripotent Stem Cells; Zscan4: transient remodeling and transcription of heterochromatin in mESCs. Systems Biology of Stem Cells: SyBoSS Double Conference, Oberstdorf, Germany.

2015 Mechanisms for genome stabilization in pluripotent stem cells. Symposium, 14th Annual Meeting of the Japanese Society for Regenerative Medicine, Reprogramming and Pluripotent Stem Cells, Tokyo, Japan.

2015 Molecular mechanisms regulating the developmental potential of early embryos and pluripotent stem cells. 60th Annual Meeting of the Japan Society for Reproductive Medicine. Invited lecture. Yokohama, Japan.

2017 38th Annual Meeting of the Japanese Society of Inflammation and Regeneration, “Disease and Stem Cells,” Osaka, Japan

2018 KEY FORUM: “Stem Cell Traits and Developmental Systems,” Kumamoto, Japan

2018 Japanese Society for Medical Mycology, “Systems Medicine and Future Medicine”

2019 Symposium of the Japan Medical Association, Japan Medical Association Hall

2019 42nd Annual Meeting of the Molecular Biology Society of Japan, Fukuoka

2021 11th Joint Symposium on New Anticancer Drug Development + 5th NEXT Medical Device Development Symposium

2021 Link-J Symposium, “Frontiers of Drug Discovery”



Invited seminars or lectures (examples)

1991 Hamburg University, Hamburg, Germany. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1991 Pasteur Institute, Paris, France. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1991 NIH, Bethesda, MD. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1991 The Jackson Laboratory, Bar Harbor, ME. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1991 Wayne State University, MI. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1991 Lawrence Livermore National Laboratory, Livermore, CA. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.

1993 University of Michigan, Ann Arbor, MI. Mouse biology with an equalized embryo cDNA library.

1995 Kresge Eye Institute, Wayne State University, Detroit, MI. Mouse biology with an equalized cDNA library.

1995 Washington University School of Medicine, St. Louis, MO: A whole genome approach for disease gene finding from human and mouse genome.

1996 Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan: Fetal placenta development and genomic imprinting.

1996 Keio University School of Medicine, Tokyo, Japan: Fetal placenta development and genomic imprinting.

1996 National Institute on Aging, National Institutes of Health, Baltimore, MD. Systematic analysis of genes expressed in the extra-embryonic tissues: Implications for gene clustering and genomic imprinting.

1997 Wayne State University, Department of Biological Sciences, Detroit, MI. Systematic analysis of genes expressed in the extra-embryonic tissues: Implications for gene clustering and genomic imprinting.

1997 Wayne State University, Center for Molecular Medicine and Genetics, Detroit, MI. A new genomics approach for developmental biology: Implantation as a model system.

1998 Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, Milwaukee, Wisconsin: A new genomics approach for developmental biology: Implantation as a model system.

1998 Wayne State University, C.S. Mott Center, Detroit, Michigan: A new genomics approach for developmental biology: Implantation as a model system

1999 Johns Hopkins University: Developmental Genomics Approach to Early Mouse Embryogenesis

2000 NICHD, NIH.

2000 Children’s Hospital of Washington, D.C.

2000 NIDCR, NIH

2000 Niigata University School of Medicine, Niigata, Japan

2000 Central Institute for Experimental Animals, Kawasaki, Japan.

2000 Carnegie Institute of Embryology, Baltimore, MD.

2001 NCI/NIH, Fredrick, MD.

2001 University of Louisville, Kentucky

2002 RIKEN Bio Resource Center, Tsukuba, Japan

2002 Washington University, St. Louis, MO
2003 Center for Genomic Regulation, Barcelona, Spain.

2004 NIH Microarray Workshop: May 12, 2004.

2004 NICHD/NIH, Bethesda, MD.

2004 Wayne State University, Detroit, Michigan, USA

2004 University of Pennsylvania, Center for Woman’s Health, Philadelphia, USA

2005 Roslin Institute, Roslin, UK

2005 Institute of Stem Cell Research (ISCR), University of Edinburgh, Edinburgh, UK
2006 Center of Regenerative Biology, University of Connecticut. CT.

2006 University of Missouri, Columbia, MO

2006 Center for Stem Cell Biology, Vanderbilt University, TN

2007 Johns Hopkins University, McKusick-Nathans Institute of Genetic Medicine, MD

2007 Carnegie Institute of Washington, Baltimore, MD

2010 NIH Scientific Directors Meeting, NIH, Bethesda, MD

2010 NIH Institute/Center Directors Meeting, NIH, Bethesda, MD

2010 Cornell University, NY

2011 City of Hope, Duarte, CA

2011 Keio University School of Medicine, Tokyo, Japan

2011 National Advisory Council on Aging, NIH, Bethesda, MD

2011 National Eye Institute (NEI), NIH, Plenary Lecture for Focus on Fellows (Annual Retreat for Postdoc Fellows), MD

2011 National Institute for Environmental Health Sciences (NIEHS), NIH, NC.

2012 Overview and Future Direction. Laboratory of Genetics, National Institute on Aging, National Institutes of Health. Baltimore, Maryland, USA.

2012 Connecting the dots: Reactivation of early embryonic genes during the generation of induced pluripotent stem cells. Office of Scientific Director’s seminar series. National Institute on Aging, NIH, Baltimore, Maryland, USA.

2012 Connecting the dots: Systems approaches to early embryos and stem cells. iCeMS Retreat, Kyoto University WPI Institute for Integrated Cell-Material Sciences, Osaka, Japan.

2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Shinanomachi Gut Forum, Tokyo, Japan.

2012 Controlling cell differentiation through understanding gene regulatory networks. Keio GCOE Final Symposium, Tokyo, Japan.

2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Department of Neurology Seminar, Keio University School of Medicine, Tokyo, Japan.

2012 What ES cells can teach us about immortality and rejuvenation. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

2012 What systems medicine aims to achieve. Symposium hosted by the Office for Promotion of Research Collaboration, Keio University: The Dawn of Systems Medicine—Toward New Collaboration among Medicine, Engineering, and Pharmacy, Tokyo, Japan.

2012 Systems biology of development and regenerative medicine. Special Lecture, Developmental Kidney Research Meeting, Tokyo, Japan.

2012 Analysis of gene networks by systems approaches and its application to stem cell engineering. Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

2012 Recapitulating the embryonic gene expression program: Reactivation of early embryonic genes by Zscan4 during iPSC generation. Seminar, National Center for Child Health and Development, Tokyo, Japan.

2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Seminar, Shonan Research Center, Takeda Pharmaceutical Company, Tokyo, Japan.

2012 What ES cells can teach us about immortality and rejuvenation. 5th Tokyo Anti-Aging Academy, Tokyo, Japan.

2012 What systems medicine aims to achieve. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.

2012 The future of increasingly globalized science: Insights gained from 20 years in the United States. Young Investigator Education Symposium, Molecular Biology Society of Japan, Fukuoka, Japan.

2012 Whole-Genome Gene Expression Profiles: Theory, Experiment, and Data Analysis. Special Lecture IV in Bioinformatics and Life Science, Tokyo Institute of Technology, Tokyo, Japan.

2013 Controlling cell differentiation through understanding gene regulatory networks. Lab Chief Lunch Seminar. National Institute on Aging, National Institutes of Health. Baltimore, Maryland, USA.

2013 Genetic and epigenetic hierarchies distinguishing pluripotent and trophoblast stem cells. Group presentation. JST-CIHR Joint Research Program on "Epigenetics of Stem Cells." Toronto, Canada.

2013 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. Agilent Genomics Forum, Tokyo, Japan.

2013 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. Metabolic Syndrome Research Meeting: Inter-Organ Networks and Vascular Biology, Tokyo, Japan.

2013 Systematic analysis of gene expression networks in pluripotent stem cells. BBSRC-JST UK-Japan Joint Program Meeting, Hokkaido, Japan.

2013 Systems medicine and medical innovation. CIO Research Group Annual Workshop, Medical Innovation Conference, Tokyo, Japan.

2013 Molecular mechanisms of early development, stem cells, and reprogramming. Open Seminar, Central Institute for Experimental Animals (CIEA), Kawasaki, Japan.

2013 Systems Medicine – Systems Medicine and Medical Care 30 Years from Now. Sixth-Year Case Review, Keio University School of Medicine, Tokyo, Japan.

2013 Cellular aging and rejuvenation learned from stem cells: Clinical applications of systems medicine. Kanto Clinical Dermatology Research Meeting, Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.

2013 The future of biomedical science and medicine enabled by systems medicine. Seminar, Hitachi Central Research Laboratory, Tokyo, Japan.

2013 Cellular aging and rejuvenation learned from stem cells. 16th Kanto Heart Seminar, Tokyo, Japan.

2013 What the COI-T Center for System Medicine and Healthcare to Establish the Global Standard for Healthy Longevity aims to achieve. Innovation Brought by Systems Medicine and Healthcare to Establish the Global Standard for Healthy Longevity. Symposium hosted by Keio University, Tokyo, Japan.

2014 What the Center for System Medicine and Healthcare to Establish the Global Standard for Healthy Longevity aims to achieve. 94th Keio Medical Society General Meeting and Symposium, Tokyo, Japan.

2014 Toward Regenerative and Rejuvenative Medicine: Systematic Manipulation and Analysis of Pluripotent Stem Cells. 2nd IRG Meeting, Tokyo, Japan.

2014 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. 6th Signal Network Research Meeting, Tokyo, Japan.

2015 Can we learn “immortality” from ES cells? Mechanism of Germline Immortality. Summer Retreat of the Extramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

2015 Functions of ZSCAN4 and its therapeutic applications. Seminar, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.

2015 Toward Systems Medicine: Healthy Longevity and Systems Medicine. 4th Oda Memorial International Symposium, National Center for Global Health and Medicine, Tokyo, Japan.

2016 The ZSCAN4 gene responsible for genome stability in stem cells: Epigenomic regulatory mechanisms and their therapeutic applications. Seminar, National Center for Child Health and Development, Tokyo, Japan.

2016 What is Systems Medicine? Systematic Analyses of Transcription Factor Networks in Mouse and Human Pluripotent Stem Cells. Biology and Therapeutic Application of Zscan4. Keio Joint Summer Research Program, Tokyo, Japan.

2016 Genome Stability and Epigenomic Regulation in Stem Cells by ZSCAN4. Special Graduate Lecture, Tokyo Medical and Dental University, Tokyo, Japan.

2016 Regulation of Genome Stability, Telomeres, and the Epigenome by ZSCAN4; Genome Stability and Epigenomic Regulation in Stem Cells by ZSCAN4. Graduate Education Course in Oncology, Kyoto University, Kyoto, Japan.

2016 Toward healthy longevity through systems medicine – Perspectives from my 30-year research experience in the US and Japan. International Symposium, Promotion of Research and Development in the Medical Field in Okinawa, Okinawa, Japan.

2016 Systems analysis of transcription factor networks: Toward precise control of differentiation in human and mouse ES cells. 135th RIKEN BioResource Center Seminar, Tsukuba, Japan.

2016 The ZSCAN4 gene responsible for genome stability in stem cells: Epigenomic regulatory mechanisms and their therapeutic applications. 35th Meeting of the Japanese Society for Molecular Pathology, Hiyoshi, Japan.

2017 6th Area Meeting & JST–OIST Joint Seminar, Okinawa

2018 Next-Generation Bio and Medical Technology Exploratory Research Meeting, University of Tokyo

2018 Central Institute for Experimental Animals, Academic Colloquium: “Differentiation Technologies of Human iPS/ES Cells into Diverse Cell Types Created by Systems Approaches: Prospects for Drug Discovery and Regenerative Medicine”

2019 Tokyo Medical Association, “Meeting to Support Medical Students, Residents, and Others”



■ List of Scientific Publications

● Peer-Reviewed Publications (*corresponding author)

1. Noda M, Ko M, Ogura A, Liu D-G, Amano T, Takano T, and Ikawa Y. (1985). Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature 318: 73-78. https://pubmed.ncbi.nlm.nih.gov/4058592/

*2. Ko MSH and Takano T. (1989). A highly inducible system of gene expression by positive feedback production of glucocorticoid receptors. DNA 8: 127-133. https://pubmed.ncbi.nlm.nih.gov/2494026/

*3. Ko MSH, Takahashi N, Sugiyama N, and Takano T. (1989). An auto-inducible vector conferring high glucocorticoid-inducibility upon stable transformant cells. Gene 84: 383-389. https://pubmed.ncbi.nlm.nih.gov/2558971/

*4. Ko MSH, Ko SBH, Takahashi N, Nishiguchi K, and Abe K. (1990). Unbiased amplification of a highly complex mixture of DNA fragments by "lone linker"-tagged PCR. Nucleic Acids Research 18: 4293-4294. https://pubmed.ncbi.nlm.nih.gov/2377489/

*5. Ko MSH, Nakauchi H, and Takahashi N. (1990). The dose-dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO Journal 9: 2834-2882. https://pubmed.ncbi.nlm.nih.gov/2167833/

*6. Ko MSH. (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs. Nucleic Acids Research 18: 5705-5711. https://pubmed.ncbi.nlm.nih.gov/2216762/

*7. Ko MSH. (1991). A stochastic model for gene induction. J Theor Biol 153: 181-184. https://pubmed.ncbi.nlm.nih.gov/1787735/

*8. Ko MSH. (1992). Induction mechanism of a single gene molecule: Stochastic or Deterministic? BioEssays 14: 341-346. . https://pubmed.ncbi.nlm.nih.gov/1637366/

*9. Takahashi N and Ko MSH. (1993). The short 3′-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome. Genomics 16, 161-168. https://pubmed.ncbi.nlm.nih.gov/8486351/

10. Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko MSH, Thurston SJ and Birkenmeier EH. (1994). Maps from two interspecific backcross DNA panels are available as a community genetic mapping resource. Mamm. Genome 5: 253-274. https://pubmed.ncbi.nlm.nih.gov/8075499/

*11. Horton JH, Hagen MD and Ko MSH. (1994). Optimized conditions for cycle sequencing of PCR products. PCR Methods & Applications 3: 359-360. https://pubmed.ncbi.nlm.nih.gov/7920241/

*12. Wang X., Qian J. and Ko MSH. (1994). Simple and robust screening of pooled YAC libraries by the restriction enzyme digestion of PCR products. Genet. Anal. Techn. Appl. 11: 63-68. https://pubmed.ncbi.nlm.nih.gov/7803131/

13. Ko MSH*, Wang X, Horton JH, Hagen MD, Takahashi N, Maezaki Y and Nadeau JH (1994). Genetic mapping of 40 cDNA clones on the mouse genome by PCR. Mamm. Genome. 5: 349-355. https://pubmed.ncbi.nlm.nih.gov/8043949/

*14. Takahashi N and Ko MSH. (1994). Towards a whole cDNA catalog: an equalized cDNA library from mouse embryos. Genomics. 23: 202-210. https://pubmed.ncbi.nlm.nih.gov/7829072/

15. Harada H, Hashimoto K and Ko MSH. (1996). The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J. Invest. Dermatology, 107: 41-43. https://pubmed.ncbi.nlm.nih.gov/8752837/

*16. Yotsumoto S, Fujiwara H, Horton JH, Mosby TA, Wang X, Cui Y and Ko MSH. (1996). Cloning and expression analyses of mouse dystroglycan gene: Specific expression in maternal decidua at the peri-implantation stage. Hum Mol Genet, 5: 1259-1267. https://pubmed.ncbi.nlm.nih.gov/8872465/

17. Harada H, Hashimoto K, Toi Y, Yotsumoto S and Ko MSH. (1997). Basal cell carcinoma occurring in multiple familial trichoepithelioma: detection of loss of heterozygosity in chromosome 9q. Arch Dermatol, 133: 666-667. https://pubmed.ncbi.nlm.nih.gov/9158430/

18. D’Esposito M, Matarazzo MR, Ciccodicola A, Strazzullo M, Mazzarella R, Quaderi NA, Fujiwara H, Ko MSH, Rowe LB, Ricco A, Archidiacono N, Rocchi M, Schlessinger D and D’Urso M. (1997). Differential expression pattern of XqPAR-linked genes SYBL1 and IL9R correlates with the structure and evolution of the region. Hum Mol Genet, 6: 1917-1923. https://pubmed.ncbi.nlm.nih.gov/9302271/

19. Srivastava AK, Pispa J, Hartung AJ, Du Y, Ezer S, Jenks T, Shimada T, Pekkanen M, Ko MSH, Thesleff I, Kere J and Schlessinger D. (1997). The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene, which reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains. Proc. Natl. Acad. Sci. USA, 94: 13069-13074. https://pubmed.ncbi.nlm.nih.gov/9371801/

20. Jaradat SA, Ko MSH and Grossman LI. (1998). Tissue specific expression and mapping of the COX7AH gene in mouse. Genomics, 49: 363-370. https://pubmed.ncbi.nlm.nih.gov/9615220/

*21. Yotsumoto S, Shimada T, Cui CY, Nakashima H, Fujiwara H and Ko MSH. (1998). Expression of Adrenomedullin, a Hypotensive Peptide, in the Trophoblast Giant Cells at the Embryo Implantation Site in Mouse. Dev Biol, 203: 264-275. https://pubmed.ncbi.nlm.nih.gov/9808778/

*22. Ko MSH, Threat TA, Wang X, Horton JH, Cui Y, Pryor E, Paris J, Wells-Smith J, Kitchen JR, Rowe LB, Eppig J, Satoh T, Brant L, Fujiwara H, Yotsumoto S and Nakashima H (1998). Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome. Hum Mol Genet, 7: 1967-78. https://pubmed.ncbi.nlm.nih.gov/9811942/

23. Schlessinger D and Ko MSH (1998). Developmental Genomics and Its Relation to Aging. Genomics. 52, 113-118. https://pubmed.ncbi.nlm.nih.gov/10348638/

24. Abe K, Ko MSH and MacGregor G.R. (1998). A systematic molecular genetic approach to study mammalian germline development. Int. J. Dev. Biol. 42, 1051-1066. https://pubmed.ncbi.nlm.nih.gov/9853837/

*25. Nakashima H, Grahovac MJ, Mazzarella R, Kitchen JR, Threat TA and Ko MSH. (1999). Two novel mouse genes – Nubp2, mapped to the t-complex on Chromosome 17, and Nubp1, mapped to Chromosome 16 – establish a new gene family of nucleotide binding proteins in eukaryotes. Genomics, 60: 152-160. https://pubmed.ncbi.nlm.nih.gov/10486206/

26. Leach R, Ko MSH, Krawetz S. (1999). Assignment of amyloid-precursor-like protein 2 gene (APLP2) to 11q24 by fluorescent in situ hybridization. Cytogenet Cell Genet, 87: 215-216. https://pubmed.ncbi.nlm.nih.gov/10702673/
*27. Yotsumoto S, Kanzaki T, Ko MSH. (2000). Beta subunit of the high affinity immunoglobulin E receptor, a candidate for atopic dermatitis, is not imprinted. Br J Dermatol, 142:370-371. https://pubmed.ncbi.nlm.nih.gov/10730778/

*28. Ko MSH, Kitchen JR, Wang X., Threat TA, Wang X, Hasegawa A, Sun T, Grahovac MJ, Kargul GJ, Lim MK, Cui Y, Sano Y, Tanaka T, Liang Y, Mason S, Paonessa PD, Sauls AD, DePalma GE, Sharara R, Rowe LB, Eppig J, Morrell C, Doi H (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development. Development, 127: 1737-1749. https://pubmed.ncbi.nlm.nih.gov/10725249/

29. Chou SR, Brownell A, Ko MSH, Kaplan J. (2000). Interferon gamma receptor gene: key role in determining accessibility of NK-triggering antigens to recognition by Self-reactive NK cells. Cell Immunol. 2000 Mar 15;200(2):88-97. https://pubmed.ncbi.nlm.nih.gov/10753500/

*30. Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood 3 WH, Becker KG, and Ko MSH (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15000 mouse developmental cDNA microarray, Proc. Natl. Acad. Sci. USA, 97: 9127-9132. https://pubmed.ncbi.nlm.nih.gov/10922068/

*31. Kargul GJ, Nagaraja R, Shimada T, Grahovac M, Lim MK, Nakashima H, Waeltz P, Ma P, Chen E, Schlessinger D and Ko MSH (2000). Eleven densely clustered genes, seven of them novel, in 176 kb of mouse t-complex DNA. Genome Res, 10: 916-923. https://pubmed.ncbi.nlm.nih.gov/10899141/

*32. Nicholson RH, Pantano S, Eliason JF, Galy A, Weiler S, Kaplan J, Hughes MR, and Ko MSH (2000). Phemx, a novel mouse gene expressed during hematopoiesis, maps to the imprinted cluster on distal chromosome 7. Genomics, 68: 13-21. https://pubmed.ncbi.nlm.nih.gov/10950922/

33. Cocchia M, Huber R, Pantano S, Chen EY, Forabosco A, Ko MSH, and Schlessinger D (2000). PLAC1, an Xq26 gene with placenta-specific expression. Genomics, 68: 305-312. https://pubmed.ncbi.nlm.nih.gov/10995572/

*34. Ko MSH (2001). Embryogenomics: developmental biology meets genomics. Trends Biotechnol. 19: 511-518. https://pubmed.ncbi.nlm.nih.gov/11711195/

*35. Kargul GJ, Dudekula DB, Qian Y, Lim MK, Jaradat SA, Tanaka TS, Carter MG, and Ko MSH (2001). Verification and initial annotation of the NIA mouse 15K cDNA clone set. Nature Genetics, 28:17-18. https://pubmed.ncbi.nlm.nih.gov/11326268/

36. Cintron VJ, Ko MSH, Chi KD, Gross JP, Srinivas PR, Goustin AS, Grunberger G (2001). Genetic mapping and functional studies of a natural inhibitor of the insulin receptor tyrosine kinase: the mouse ortholog of human alpha2-HS glycoprotein. Int J Exp Diabetes Res, 1: 249-263. https://pubmed.ncbi.nlm.nih.gov/11467416/

*37. Piao Y, Ko NT, Lim MK, Ko MSH (2001). Construction of long-transcript enriched cDNA libraries from submicrogram amounts of total RNAs by a universal PCR amplification method. Genome Res. 11: 1553-1558. https://pubmed.ncbi.nlm.nih.gov/11544199/

38. Barrett T, Xie T, Piao Y, Dillon-Carter O, Kargul GJ, Lim MK, Chrest FJ, Wersto R, Rowley DL, Juhaszova M, Zhou L, Vawter MP, Becker KG, Cheadle C, Wood WH 3rd, McCann UD, Freed WJ, Ko MSH, Ricaurte GA, Donovan DM (2001). A Murine Dopamine Neuron-Specific cDNA Library and Microarray: Increased COXI Expression during Methamphetamine Neurotoxicity. Neurobiol Dis. 8: 822-833. https://pubmed.ncbi.nlm.nih.gov/11592851/

39. Hudson TJ, Church DM, Greenaway S, Nguyen H, Cook A, Steen RG, Van Etten WJ, Castle AB, Strivens MA, Trickett P, Heuston C, Davison C, Southwell A, Hardisty R, Varela-Carver A, Haynes AR, Rodriguez-Tome P, Doi H, Ko MSH, Pontius J, Schriml L, Wagner L, Maglott D, Brown SD, Lander ES, Schuler G, Denny P (2001). A radiation hybrid map of mouse genes. Nat Genet. 29: 201-205. https://pubmed.ncbi.nlm.nih.gov/11586302/

*40. Sano Y, Shimada T, Nakashima H, Nicholson RH, Eliason JF, Kocarek TA, Ko MSH (2001). Random Monoallelic Expression of Three Genes Clustered within 60 kb of Mouse t Complex Genomic DNA. Genome Res. 11: 1833-1841. https://pubmed.ncbi.nlm.nih.gov/11691847/

41. Leach R, Duniec-Dmuchowski Z, Tanaka T, Ko MSH, Krawetz SA. Assignment of OVCOV1 (alias CGI-15) to human chromosome 20 band q13.1–>q13.2 by fluorescent in situ hybridization. Cytogenet Cell Genet. 2001;94(3-4):252-3. https://pubmed.ncbi.nlm.nih.gov/11856893/

42. Cui CY, Durmowicz M, Tanaka TS, Hartung AJ, Tezuka T, Hashimoto K, Ko MSH, Srivastava AK, Schlessinger D. (2002). EDA targets revealed by skin gene expression profiles of wild-type, Tabby and Tabby EDA-A1 transgenic mice. Hum Mol Genet. 2002 Jul 15;11(15):1763-73. https://pubmed.ncbi.nlm.nih.gov/12095918/

43. Leach RE, Duniec-Dmuchowski ZM, Pesole G, Tanaka TS, Ko MSH, Armant RD, Krawetz SA. (2002). Identification, molecular characterization, and tissue expression of OVCOV1. Mamm Genome 13: 619-24. https://pubmed.ncbi.nlm.nih.gov/12461647/

*44. VanBuren V, Piao Y, Dudekula DB, Qian Y, Carter MG, Martin PR, Stagg CA, Bassey UC, Aiba K, Hamatani T, Kargul GJ, Luo AG, Kelso J, Hide W and Ko MSH. (2002). Assembly, verification, and initial annotation of the NIA mouse 7.4K cDNA clone set. Genome Res 12: 1999-2003. https://pubmed.ncbi.nlm.nih.gov/12466305/

*45. Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA, Usuda M, Yokota T, Niwa H, Rossant J, and Ko MSH. (2002). Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 12: 1921-8. https://pubmed.ncbi.nlm.nih.gov/12466296/

46. Chen G., Jaradat SA, Banerjee N, Tanaka TS, Ko MSH, and Zhang MQ (2002). Evaluation and Comparison of Clustering Algorithms in Analyzing ES Cell Gene Expression Data. Statistica Sinica 12: 241-262.

*47. Suemizu H, Aiba H, Yoshikawa T, Sharov AA, Shimozawa N, Tamaoki N, and Ko MSH. (2003). Expression profiling of placentomegaly associated with nuclear transplantation of mouse ES cells. Dev Biol 253: 36-53. https://pubmed.ncbi.nlm.nih.gov/12490196/

*48. Kimber WL, Puri N, Borgmeyer C, Ritter D, Sharov A, Seidman M, and Ko MSH. (2003). Efficacy of 2-methoxyethoxy (2’-MOE)-modified antisense oligonucleotides for the study of mouse preimplantation development. Reprod Biomed Online 6, 318-322. https://pubmed.ncbi.nlm.nih.gov/12735867/

*49. Carter MG, Hamatani T, Sharov AA, Carmack CE, Qian Y, Ko NT, Dudekula DB, Brzoska PM, Hwang SS, and Ko MSH. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling. Genome Res. 13: 1011-21. https://pubmed.ncbi.nlm.nih.gov/12727912/

50. Galaviz-Hernandez C, Stagg C, de Ridder G, Tanaka TS, Ko MSH, Schlessinger D, Nagaraja R. (2003). Plac8 and Plac9, novel placental-enriched genes identified through microarray analysis. Gene 309: 81-9. https://pubmed.ncbi.nlm.nih.gov/12758124/

51. Buttitta L, Tanaka TS, Chen AE, Ko MSH, and Fan C.M. (2003). Microarray analysis of somitogenesis reveals novel targets of different wnt signaling pathways in the somitic mesoderm. Dev Biol. 2003 Jun 1;258(1):91-104. https://pubmed.ncbi.nlm.nih.gov/12781685/

*52. Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D’Urso M, Kelso J, Hide W, Ko MSH. (2003). Transcriptome Analysis of Mouse Stem Cells and Early Embryos. PLoS Biol. 1: 410-419. https://pubmed.ncbi.nlm.nih.gov/14691545/

*53. Carter MG, Piao Y, Dudekula DB, Qian Y, VanBuren V, Sharov AA, Tanaka TS, Martin PR, Bassey UC, Stagg CA, Aiba K, Hamatani T, Matoba R, argul GJ and Ko MSH (2003). The NIA cDNA Project in mouse stem cells and early embryos. C R Biol. 2003 Oct-Nov;326(10-11):931-40. https://pubmed.ncbi.nlm.nih.gov/14744099/

*54. Hamatani T, Carter MG, Sharov AA and Ko MSH. (2004). Dynamics of global gene expression changes during mouse preimplantation development. Dev. Cell: 6, 117-131. [Published online Dec. 18, 2003] https://pubmed.ncbi.nlm.nih.gov/14723852/

55. Abe K, Yuzuriha M, Sugimoto M, Ko MSH, Brathwaite M, Waeltz P, Nagaraja R (2004). Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5. Mamm Genome 15: 265-76. https://pubmed.ncbi.nlm.nih.gov/15112104/

56. Hamatani T, Daikoku T, Wang H, Matsumoto H, Carter MG, Ko MSH, Dey SK (2004). Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10326-31. https://pubmed.ncbi.nlm.nih.gov/15232000/

*57. Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MSH (2004). Age-associated alteration of gene expression patterns in mouse oocytes. Human Molecular Genetics; 13(19):2263-78. https://pubmed.ncbi.nlm.nih.gov/15317747/

58. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J; MGC Project Team. (2004). The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. https://pubmed.ncbi.nlm.nih.gov/15489334/

*59. Ko MSH (2004). Embryogenomics of preimplantation mammalian development: Current Status. Reproduction, Fertility and Development 16: 79-85. https://pubmed.ncbi.nlm.nih.gov/14972105/

*60. Tanaka TS, Ko MSH. A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst. Eur J Obstet Gynecol Reprod Biol. 2004 Jul 1;115 Suppl 1:S85-91. https://pubmed.ncbi.nlm.nih.gov/15196723/

61. Ottolenghi, C., Uda, M., Hamatani, T., Crisponi, L., Garcia, Jose-Elias., Ko, M.S.H., Pilia, G., Sforza, C., Schlessinger, D., and Forabosco, A (2004). Aging of Oocyte, Ovary and Human Reproduction. Ann. New York Acad. Sci. 1034: 117-131. https://pubmed.ncbi.nlm.nih.gov/15731305/

62. Herrera L, Ottolenghi C, Garcia-Ortiz JE, Pellegrini M, Manini F, Ko MS, Nagaraja R, Forabosco A, Schlessinger D. (2005). Mouse ovary developmental RNA and protein markers from gene expression profiling. Dev Biol. 2005 Mar 15;279(2):271-90. https://pubmed.ncbi.nlm.nih.gov/15733658/

63. Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG, Witzel SD, Okano H, Ko MS, Ohlsson R, Longo DL, Feinberg AP. (2005). Loss of Imprinting of Igf2 Alters Intestinal Maturation and Tumorigenesis in Mice. Science. 2005 Feb 24. https://pubmed.ncbi.nlm.nih.gov/15731405/

*64. Sharov AA, Dudekula DB, Ko MSH (2005). A web-based tool for principal component and significance analysis of microarray data. Bioinformatics. 2005 May 15;21(10):2548-9. https://pubmed.ncbi.nlm.nih.gov/15734774/

*65. Sharov AA, Dudekula DB, and Ko MSH (2005). Genome-wide assembly and analysis of alternative transcripts in mouse. Genome Res. 2005 May;15(5):748-54. https://pubmed.ncbi.nlm.nih.gov/15867436/

66. Akagi T, Usuda M, Matsuda T, Ko MSH, Niwa H, Asano M, Koide H, and Yokota T. (2005). Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells. Biochem Biophys Res Commun. 2005 May 27; 331(1): 23-30. https://pubmed.ncbi.nlm.nih.gov/15845352/

67. Tamura T, Thotakura P, Tanaka TS, Ko MSH, Ozato K (2005). Identification of target genes and a unique cis-element regulated by IRF-8 in developing macrophages. Blood. 2005 Jun 9. https://pubmed.ncbi.nlm.nih.gov/15947094/

*68. Carter MG, Sharov AA, VanBuren V, Dudekula DB, Carmack CE, Nelson C, Ko MSH (2005). Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray. Genome Biol. 2005;6(7):R61. https://pubmed.ncbi.nlm.nih.gov/15998450/

69. Ko MSH (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions. Reprod. Biomed. Online 10 Suppl 1: 80-87. https://pubmed.ncbi.nlm.nih.gov/15820015/

70. McMahan J, Cohen J, Ko MSH, Johnson M, Robertson J, Murphy T, Brinsden P, Hussein F, Savulescu J, McLaren A, McLean S, Harris J, Schulman J, Edwards R, Pedersen R, Stock G, Grudzinskas G, and Boivin J (2005). Discussion (day 2 session 2): Modern genetics and the human embryo in vitro. Reprod. Biomed. Online 10 Suppl 1: 107-110. https://pubmed.ncbi.nlm.nih.gov/15820019/

*71. Yoshikawa T, Piao Y, Zhong J, Matoba R, Carter MG, Wang Y, Goldberg I, Ko MSH (2006). High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization. Gene Expr Patterns. 2006 Jan;6(2):213-24. https://pubmed.ncbi.nlm.nih.gov/16325481/

*72. Aiba K, Sharov AA, Carter MG, Foroni C, Vescovi AL, Ko MSH (2005). Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells. Stem Cells. 2005 Dec 15; https://pubmed.ncbi.nlm.nih.gov/16357342/

73. Park JM, Kohn MJ, Bruinsma MW, Vech C, Intine RV, Fuhrmann S, Grinberg A, Mukherjee I, Love PE, Ko MSH, Depamphilis ML, Maraia RJ (2006). The Multifunctional RNA-Binding Protein La Is Required for Mouse Development and for the Establishment of Embryonic Stem Cells. Mol Cell Biol. 2006 Feb;26(4):1445-51. https://pubmed.ncbi.nlm.nih.gov/16449655/

74. Das B, Cai L, Carter MG, Piao YL, Sharov AA, Ko MSH, Brown DD (2006). Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles. Dev Biol. 2006 Feb 1; https://pubmed.ncbi.nlm.nih.gov/16458881/

*75. Ko MSH (2006). Expression profiling of the mouse early embryo: Reflections and perspectives. Dev Dyn. 2006 May 31; https://pubmed.ncbi.nlm.nih.gov/16739220/

76. Rogers NT, Halet G, Piao Y, Carroll J, Ko MSH and Swann K (2006). A Ca2+ signal during mouse egg activation affects preimplantation development, gene expression patterns, and blastocyst quality. Reproduction. 2006 Jul;132(1):45-57. https://pubmed.ncbi.nlm.nih.gov/16816332/

*77. Tanaka TS, Lopez de Silanes I, Sharova LV, Akutsu H, Yoshikawa T, Amano H, Yamanaka S, Gorospe M, Ko MSH (2006). Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative RNA-binding protein with broad RNA targets. Dev Growth Differ. 2006 Aug;48(6):381-90. https://pubmed.ncbi.nlm.nih.gov/16872451/

*78. Falco G, Stanghellini I, Ko MS (2006). Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos. Reprod Biomed Online. 2006 Sep;13(3):394-403. https://pubmed.ncbi.nlm.nih.gov/16984773/

*79. Aiba K, Carter MG, Matoba R, Ko MSH (2006). Genomic approaches to early embryogenesis and stem cell biology. Semin Reprod Med. 2006 Nov;24(5):330-9. https://pubmed.ncbi.nlm.nih.gov/17123228/

*80. Sharov AA, Dudekula DB, Ko MSH (2006). CisView: a browser and database of cis-regulatory modules predicted in the mouse genome. DNA Res. 2006 Jun 30;13(3):123-34. https://pubmed.ncbi.nlm.nih.gov/16980320/

81. Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H (2006). Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 2006 Oct;26(20):7772-82. https://pubmed.ncbi.nlm.nih.gov/16954384/

82. Hamatani T, Ko MSH, Yamada M, Kuji N, Mizusawa Y, Shoji M, Hada T, Asada H, Maruyama T, Yoshimura Y (2006). Global gene expression profiling of preimplantation embryos. Hum Cell. 2006 Aug;19(3):98-117. https://pubmed.ncbi.nlm.nih.gov/17204093/

*83. Matoba R, Niwa H, Masui S, Ohtsuka S, Carter MG, Sharov AA, Ko MS (2006). Dissecting oct3/4-regulated gene networks in embryonic stem cells by expression profiling. PLoS ONE. 2006 Dec 20;1:e26. https://pubmed.ncbi.nlm.nih.gov/17183653/

84. Ko MSH and McLaren A (2006). Epigenetics of germ cells, stem cells, and early embryos. Meeting Report. Dev. Cell 10, 161-166. https://pubmed.ncbi.nlm.nih.gov/16506346/

85. Ko, MSH (2006). Meet our Editor. Reprod. Biomed. Online. 12: 143.

86. Sharov AA and Ko MSH (2007). Previews: Human ES cell profiling broadens the reach of bivalent domains. Cell Stem Cell 1, 237-238. https://pubmed.ncbi.nlm.nih.gov/18371354/

87. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 2007 Jun;9(6):625-35. https://pubmed.ncbi.nlm.nih.gov/17515932/

*88. Falco G, Lee SL, Stanghellini I, Bassey UC, Hamatani T, Ko MS (2007). Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells. Dev Biol. 2007 Jul 15;307(2):539-50. Epub 2007 May 8. https://pubmed.ncbi.nlm.nih.gov/17553482/

*89. Sharova LV, Sharov AA, Piao Y, Shaik N, Sullivan T, Stewart CL, Hogan BL, Ko MS (2007). Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains. Dev Biol. 2007 Jul 15;307(2):446-59. https://pubmed.ncbi.nlm.nih.gov/17560561/

90. Ulloa-Montoya F, Kidder BL, Pauwelyn KA, Chase LG, Luttun A, Crabbe A, Geraerts M, Sharov AA, Piao Y, Ko MS, Hu WS, Verfaillie CM (2007). Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity. Genome Biol. 2007 Aug 6;8(8):R163 https://pubmed.ncbi.nlm.nih.gov/17683608/

91. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta EG, Boheler KR, Xu X, Mattson MP, Falco G, Ko MS, Schlessinger D, Firman J, Kummerfeld SK, Wood WH 3rd, Zonderman AB, Kim SK, Becker KG. (2007). AGEMAP: a gene expression database for aging in mice. PLoS Genet. 2007 Nov 30;3(11):e201. https://pubmed.ncbi.nlm.nih.gov/18081424/

92. Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP (2007). Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20926-31. https://pubmed.ncbi.nlm.nih.gov/18087038/

*93. Carter MG, Stagg CA, Falco G, Yoshikawa T, Bassey UC, Aiba K, Sharova LV, Shaik N, Ko MS (2007). An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells. Gene Expr Patterns. 2007 Nov 4; https://pubmed.ncbi.nlm.nih.gov/18178135/

*94. Yan Z, Wang Z, Sharova L, Sharov AA, Ling C, Piao Y, Aiba K, Matoba R, Wang W, and Ko MS (2008). BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells. 2008 May;26(5):1155-65. https://pubmed.ncbi.nlm.nih.gov/18323406/

95. Vallée M, Aiba K, Piao Y, Palin MF, Ko MS, and Sirard MA (2008). Comparative analysis of oocyte transcript profiles reveals a high degree of conservation among species. Reproduction. 2008 Apr;135(4):439-48. https://pubmed.ncbi.nlm.nih.gov/18367505/

96. Masui S, Ohtsuka S, Yagi R, Takahashi K, Ko MS, and Niwa H (2008). Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells. BMC Dev Biol. 2008 Apr 24;8:45. https://pubmed.ncbi.nlm.nih.gov/18433507/

*97. Sharov AA, Falco G, Piao Y, Poosala S, Becker KG, Zonderman AB, Longo DL, Schlessinger D, and Ko MSH (2008). Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary. BMC Biol. 2008 Jun 3;6:24. https://pubmed.ncbi.nlm.nih.gov/18522719/

*98. Sharov AA, Masui S, Sharova LV, Piao Y, Aiba K, Matoba R, Xin L, Niwa H, and Ko MS (2008). Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data. BMC Genomics. 2008 Jun 3;9:269. https://pubmed.ncbi.nlm.nih.gov/18522731/

99. Tsuji Y, Yoshimura N, Aoki H, Sharov AA, Ko MS, Motohashi T, and Kunisada T (2008). Maintenance of undifferentiated mouse embryonic stem cells in suspension by the serum- and feeder-free defined culture condition. Dev Dyn. 2008 Aug;237(8):2129-38. https://pubmed.ncbi.nlm.nih.gov/18624284/

*100. Yellaboina S, Dudekula DB, and Ko MSH (2008). Prediction of evolutionarily conserved interologs in Mus musculus. BMC Genomics. 2008 Oct 8;9:465. https://pubmed.ncbi.nlm.nih.gov/18842131/

101. Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, and Wu C (2008). Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet. 2008 Oct;4(10):e1000241. https://pubmed.ncbi.nlm.nih.gov/18974875/

*102. Aiba K, Nedorezov T, Piao Y, Nishiyama A, Matoba R, Sharova LV, Sharov AA, Yamanaka S, Niwa H, Ko MS (2009). Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells. DNA Res. 2009 Feb;16(1):73-80. Epub 2008 Dec 26. https://pubmed.ncbi.nlm.nih.gov/19112179/

103. Kunisada M, Cui CY, Piao Y, Ko MS, Schlessinger D (2009). Requirement for Shh and Fox family genes at different stages in sweat gland development. Hum Mol Genet. 2009 May 15;18(10):1769-78. Epub 2009 Mar 6. https://pubmed.ncbi.nlm.nih.gov/19270025/

104. Sun C, Nakatake Y, Akagi T, Ura H, Matsuda T, Nishiyama A, Koide H, Ko MS, Niwa H, Yokota T (2009). Dax1 Binds to Oct3/4 and Inhibits Its Transcriptional Activity in Embryonic Stem Cells. Mol Cell Biol. 2009 Jun 15. https://pubmed.ncbi.nlm.nih.gov/19528230/

*105. Stanghellini I, Falco G, Lee SL, Monti M, Ko MS (2009). Trim43a, Trim43b, and Trim43c: Novel mouse genes expressed specifically in mouse preimplantation embryos. Gene Expr Patterns. 2009 Dec;9(8):595-602. https://pubmed.ncbi.nlm.nih.gov/19703589/

*106. Sharov AA, Ko MS (2009). Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res. 2009 Oct;16(5):261-73. https://pubmed.ncbi.nlm.nih.gov/19740934/

107. Vallejo G, Maschi D, Mestre-Citrinovitz AC, Aiba K, Maronna R, Yohai V, Ko MS, Beato M, Saragüeta P (2010). Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells. J Cell Physiol. 2010 Jan;222(1):127-37. https://pubmed.ncbi.nlm.nih.gov/19780023/

*108. Nishiyama A, Xin L, Sharov AA, Thomas M, Mowrer G, Meyers E, Piao Y, Mehta S, Yee S, Nakatake Y, Stagg C, Sharova L, Correa-Cerro LS, Bassey U, Hoang H, Kim E, Tapnio R, Qian Y, Dudekula D, Zalzman M, Li M, Falco G, Yang HT, Lee SL, Monti M, Stanghellini I, Islam MN, Nagaraja R, Goldberg I, Wang W, Longo DL, Schlessinger D, Ko MS (2009). Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009 Oct 2;5(4):420-33. https://pubmed.ncbi.nlm.nih.gov/19796622/

*109. Sharova LV, Sharov AA, Nedorezov T, Piao Y, Shaik N, Ko MS (2009). Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res 2009; 16(1): 45-58. https://pubmed.ncbi.nlm.nih.gov/19001483/

110. Canham MA, Sharov AA, Ko MS, Brickman JM (2010). Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript. PLoS Biol 2010; 8(5): e1000379. https://pubmed.ncbi.nlm.nih.gov/20520791/

111. Cui CY, Kunisada M, Piao Y, Childress V, Ko MS, Schlessinger D (2010). Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair. PLoS One 2010; 5(4): e10009. https://pubmed.ncbi.nlm.nih.gov/20386733/

*112. Sharov AA, Piao Y, Ko MS (2010). Gene expression profiling of mouse embryos with microarrays. Methods Enzymol 2010; 477: 511-41. https://pubmed.ncbi.nlm.nih.gov/20699157/

113. Vong QP, Liu Z, Yoo JG, Chen R, Xie W, Sharov AA, Fan CM, Liu C, Ko MS, Zheng Y (2010). A role for borg5 during trophectoderm differentiation. Stem Cells 2010; 28(6): 1030-8. https://pubmed.ncbi.nlm.nih.gov/20506138/

*114. Zalzman M, Falco G, Sharova LV, Nishiyama A, Thomas M, Lee SL, Stagg CA, Hoang HG, Yang HT, Indig FE, Wersto RP, Ko MS (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 2010; 464(7290): 858-63. https://pubmed.ncbi.nlm.nih.gov/20336070/

*115. Correa-Cerro LS, Piao Y, Sharov AA, Nishiyama A, Cadet JS, Yu H, Sharova LV, Xin L, Hoang HG, Thomas M, Qian Y, Dudekula DB, Meyers E, Binder BY, Mowrer G, Bassey U, Longo DL, Schlessinger D, Ko MS (2011). Generation of mouse ES cell lines engineered for the forced induction of transcription factors. Sci Rep 2011; 1: 167. https://pubmed.ncbi.nlm.nih.gov/22355682/

*116. Kim Y, Sharov AA, McDole K, Cheng M, Hao H, Fan CM, Gaiano N, Ko MS, Zheng Y (2011). Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. Science 2011; 334(6063): 1706-10. https://pubmed.ncbi.nlm.nih.gov/22116031/

*117. Sharov AA, Nishiyama A, Piao Y, Correa-Cerro LS, Amano T, Thomas M, Mehta S, Ko MS (2011). Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity. BMC Genomics 2011; 12: 102. https://pubmed.ncbi.nlm.nih.gov/21306619/

118. Cui CY, Childress V, Piao Y, Michel M, Johnson AA, Kunisada M, Ko MS, Kaestner KH, Marmorstein AD, Schlessinger D (2012). Forkhead transcription factor FoxA1 regulates sweat secretion through Bestrophin 2 anion channel and Na-K-Cl cotransporter 1. Proc Natl Acad Sci U S A 2012; 109(4): 1199-203. https://pubmed.ncbi.nlm.nih.gov/22223659/

119. Hammachi F, Morrison GM, Sharov AA, Livigni A, Narayan S, Papapetrou EP, O’Malley J, Kaji K, Ko MS, Ptashne M, Brickman JM (2012). Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency. Cell Rep 2012; 1(2): 99-109. https://pubmed.ncbi.nlm.nih.gov/22832160/

*120. Hirata T, Amano T, Nakatake Y, Amano M, Piao Y, Hoang HG, Ko MS (2012). Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells. Sci Rep 2012; 2: 208. https://pubmed.ncbi.nlm.nih.gov/22355722/

121. Ko SB, Azuma S, Yoshikawa T, Yamamoto A, Kyokane K, Ko MS, Ishiguro H (2012). Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. Front Physiol 2012; 3: 415. https://pubmed.ncbi.nlm.nih.gov/23133422/

122. States JC, Singh AV, Knudsen TB, Rouchka EC, Ngalame NO, Arteel GE, Piao Y, Ko MS (2012). Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis. PLoS One 2012; 7(6): e38713. https://pubmed.ncbi.nlm.nih.gov/22719926/

123. Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK (2012). Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem 2012; 287(38): 32288-97. https://pubmed.ncbi.nlm.nih.gov/22833670/

*124. Yang HT, Ko MS (2012). Stochastic modeling for the expression of a gene regulated by competing transcription factors. PLoS One 2012; 7(3): e32376. https://pubmed.ncbi.nlm.nih.gov/22431973/

*125. Hung SS, Wong RC, Sharov AA, Nakatake Y, Yu H, Ko MS (2013). Repression of global protein synthesis by eif1a-like genes that are expressed specifically in the two-cell embryos and the transient zscan4-positive state of embryonic stem cells. DNA Res 2013; 20(4): 391-402. https://pubmed.ncbi.nlm.nih.gov/23649898/

126. Ko SB, Azuma S, Yokoyama Y, Yamamoto A, Kyokane K, Niida S, Ishiguro H, Ko MS (2013). Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas. Am J Physiol Gastrointest Liver Physiol 2013; 304(12): G1103-16. https://pubmed.ncbi.nlm.nih.gov/23599043/

127. Monti M, Zanoni M, Calligaro A, Ko MS, Mauri P, Redi CA (2013). Developmental arrest and mouse antral not-surrounded nucleolus oocytes. Biol Reprod 2013; 88(1): 2. https://pubmed.ncbi.nlm.nih.gov/23136301/

128. Morgani SM, Canham MA, Nichols J, Sharov AA, Migueles RP, Ko MS, Brickman JM (2013). Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep 2013; 3(6): 1945-57. https://pubmed.ncbi.nlm.nih.gov/23746443/

*129. Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T, Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS (2013). Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep 2013; 3: 1390. https://pubmed.ncbi.nlm.nih.gov/23462645/

*130. Amano T, Hirata T, Falco G, Monti M, Sharova LV, Amano M, Sheer S, Hoang HG, Piao Y, Stagg CA, Yamamizu K, Akiyama T, Ko MS (2013). Zscan4 restores the developmental potency of embryonic stem cells. Nat Commun 2013; 4: 1966. https://pubmed.ncbi.nlm.nih.gov/23739662/

131. Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, Yang J, Sharov A, Srikantan S, Yang J, Fox D, 3rd, Qian Y, Martindale JL, Piao Y, Machamer J, Joshi SR, Mohanty S, Shaw AC, Lloyd TE, Brown GW, Ko MS, Gorospe M, Zou S, Wang W (2013). Top3beta is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci 2013. https://pubmed.ncbi.nlm.nih.gov/23912945/

132. Livigni A, Peradziryi H, Sharov AA, Chia G, Hammachi F, Migueles RP, Sukparangsi W, Pernagallo S, Bradley M, Nichols J, Ko MS, Brickman JM (2013). A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. Curr Biol. 2013 Nov 18;23(22):2233-44. https://pubmed.ncbi.nlm.nih.gov/24210613/

*133. Yamamizu K, Piao Y, Sharov AA, Zsiros V, Yu H, Nakazawa K, Schlessinger D, Ko MS (2013). Identification of transcription factors for lineage-specific ESC differentiation. Stem Cell Reports. 2013 Nov 27;1(6):545-59. https://pubmed.ncbi.nlm.nih.gov/24371809/

134. Sherman-Baust CA, Kuhn E, Valle BL, Shih IeM, Kurman RJ, Wang TL, Amano T, Ko MS, Miyoshi I, Araki Y, Lehrmann E, Zhang Y, Becker KG, Morin PJ (2014). A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 2014 Jul;233(3):228-37. https://pubmed.ncbi.nlm.nih.gov/24652535/

*135. Piao Y, Hung SS, Lim SY, Wong RC, Ko MS (2014). Efficient generation of integration-free human induced pluripotent stem cells from keratinocytes by simple transfection of episomal vectors. Stem Cells Transl Med. 2014 Jul;3(7):787-91. https://pubmed.ncbi.nlm.nih.gov/24904173/

*136. Sharov AA, Nishiyama A, Qian Y, Dudekula DB, Longo DL, Schlessinger D, Ko MS (2014). Chromatin properties of regulatory DNA probed by manipulation of transcription factors. J Comput Biol. 2014 Aug;21(8):569-77. https://pubmed.ncbi.nlm.nih.gov/24918633/

*137. Yamamizu K, Schlessinger D, Ko MS (2014). SOX9 accelerates ESC differentiation to three germ layer lineages by repressing SOX2 expression through P21 (WAF1/CIP1). Development. 2014 Nov;141(22):4254-66. https://pubmed.ncbi.nlm.nih.gov/25371362/

*138. Sharov AA, Schlessinger D, Ko MS (2015). ExAtlas: An interactive online tool for meta-analysis of gene expression data. J Bioinform Comput Biol. 2015 Dec;13(6):1550019. https://pubmed.ncbi.nlm.nih.gov/26223199/

*139. Amano T, Jeffries E, Amano M, Ko AC, Yu H, Ko MS (2015). Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. DNA Res. 2015 Oct;22(5):331-42. https://pubmed.ncbi.nlm.nih.gov/26324424/

*140. Akiyama T, Xin L, Oda M, Sharov AA, Amano M, Piao Y, Cadet JS, Dudekula DB, Qian Y, Wang W, Ko SB, Ko MS (2015). Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells. DNA Res. 2015 Oct;22(5):307-18. https://pubmed.ncbi.nlm.nih.gov/26324425/

141. Motohashi T, Watanabe N, Nishioka M, Nakatake Y, Yulan P, Mochizuki H, Kawamura Y, Ko MS, Goshima N, Kunisada T (2016). Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells. Biol Open. 2016 Feb 12;5(3):311-22. https://pubmed.ncbi.nlm.nih.gov/26873953/

*142. Sharova LV, Sharov AA, Piao Y, Stagg CA, Amano T, Qian Y, Dudekula D, Schlessinger D, Ko MS (2016). Emergence of undifferentiated colonies from mouse embryonic stem cells undergoing differentiation by retinoic acid treatment. In Vitro Cell Dev Biol Anim. 2016 May;52(5):616-24. https://pubmed.ncbi.nlm.nih.gov/27130680/

*143. Yamamizu K, Sharov AA, Piao Y, Amano M, Yu H, Nishiyama A, Dudekula DB, Schlessinger D, Ko MS (2016). Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines. Sci Rep. 2016 May 6;6:25667. https://pubmed.ncbi.nlm.nih.gov/27150017/

*144. Ko MS (2016). Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4. Curr Top Dev Biol. 2016;120:103-24. https://pubmed.ncbi.nlm.nih.gov/27475850/

*145. Ishiguro KI, Nakatake Y, Chikazawa-Nohtomi N, Kimura H, Akiyama T, Oda M, Ko SB, Ko MS (2016). Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos. In Vitro Cell Dev Biol Anim. 2016 Oct 3. https://pubmed.ncbi.nlm.nih.gov/27699651/

*146. Ishiguro KI, Monti M, Akiyama T, Kimura H, Chikazawa-Nohtomi N, Sakota M, Sato S, Redi CA, Ko SB, Ko MS (2016). Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis. In Vitro Cell Dev Biol Anim. 2016 Oct 3. https://pubmed.ncbi.nlm.nih.gov/27699653/

147. Teratani-Ota Y, Yamamizu K, Piao Y, Sharova L, Amano M, Yu H, Schlessinger D, Ko MS, Sharov AA (2016). Induction of specific neuron types by overexpression of single transcription factors. In Vitro Cell Dev Biol Anim. 2016 Oct;52(9):961-973. https://pubmed.ncbi.nlm.nih.gov/27251161/

*148. Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SB, Ko MS (2016). Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells. Development. 2016 Oct 15;143(20):3674-3685. https://pubmed.ncbi.nlm.nih.gov/27802135/

*149. Hirayama M, Ko SB, Kawakita T, Akiyama T, Goparaju SK, Soma A, Nakatake Y, Sakota M, Chikazawa-Nohtomi N, Shimmura S, Tsubota K, Ko MS (2017). Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells. npj Aging and Mechanisms of Disease 2017; 3: 1. https://pubmed.ncbi.nlm.nih.gov/28649419/

*150. Goparaju SK, Kohda K, Ibata K, Soma A, Nakatake Y, Akiyama T, Wakabayashi S, Matsushita M, Sakota M, Kimura H, Yuzaki M, Ko SB, Ko MS (2017). Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci Rep. 2017 Feb 13;7:42367. https://pubmed.ncbi.nlm.nih.gov/28205555/

151. Matsumoto H, Kiryu H, Furusawa C, Ko MS, Ko SB, Gouda N, Hayashi T, Nikaido I (2017). SCODE: An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation. Bioinformatics. 2017 Apr 4. https://pubmed.ncbi.nlm.nih.gov/28379368/

152. Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E (2017). Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. Sci Rep. 2017 Apr 20;7:46580. https://pubmed.ncbi.nlm.nih.gov/28425456/

*153. Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Ko MSH (2017). Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells. Stem Cells Int. 2017; 2017:7215010. https://pubmed.ncbi.nlm.nih.gov/28491098/

*154. Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH (2017). Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun. 2017 Aug 19;490(2):296-301. https://pubmed.ncbi.nlm.nih.gov/28610919/

*155. Akiyama T, Sato S, Chikazawa-Nohtomi N, Soma A, Kimura H, Wakabayashi S, Ko SBH, Ko MSH (2018). Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing. Sci Rep. 2018 Jan 19;8(1):1189. https://pubmed.ncbi.nlm.nih.gov/29352121/

156. Ida H, Akiyama T, Ishiguro K, Goparaju SK, Nakatake Y, Chikazawa-Nohtomi N, Sato S, Kimura H, Yokoyama Y, Nagino M, Ko MSH, Ko SBH (2018). Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors. Stem Cell Res Ther. 2018 Oct 25;9(1):277. https://pubmed.ncbi.nlm.nih.gov/30359326/

*157. Hiratsuka K, Monkawa T, Akiyama T, Nakatake Y, Oda M, Goparaju SK, Kimura H, Chikazawa-Nohtomi N, Sato S, Ishiguro K, Yamaguchi S, Suzuki S, Morizane R, Ko SBH, Itoh H, Ko MSH (2019). Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. Sci Rep. 2019 Jan 29;9(1):913. https://pubmed.ncbi.nlm.nih.gov/30696889/

158. Nishihara K, Shiga T, Nakamura E, Akiyama T, Sasaki T, Suzuki S, Ko MSH, Tada N, Okano H, Akamatsu W (2019). Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression. Stem Cell Reports. 2019 Feb 12;12(2):305-318. https://pubmed.ncbi.nlm.nih.gov/30713040/

159. Ishiguro KI, Matsuura K, Tani N, Takeda N, Usuki S, Yamane M, Sugimoto M, Fujimura S, Hosokawa M, Chuma S, Ko MSH, Araki K, Niwa H (2020). MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. Dev Cell. 2020 Feb 24;52(4):429-445.e10. https://pubmed.ncbi.nlm.nih.gov/32032549/

*160. Nakatake Y, Ko SBH, Sharov AA, Wakabayashi S, Murakami M, Sakota M, Chikazawa N, Ookura C, Sato S, Ito N, Ishikawa-Hirayama M, Mak SS, Jakt LM, Ueno T, Hiratsuka K, Matsushita M, Goparaju SK, Akiyama T, Ishiguro KI, Oda M, Gouda N, Umezawa A, Akutsu H, Nishimura K, Matoba R, Ohara O, Ko MSH (2020). Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors. Cell Rep. 2020 May 19;31(7):107655. https://pubmed.ncbi.nlm.nih.gov/32433964/

161. Tanosaki S, Tohyama S, Fujita J, Someya S, Hishiki T, Matsuura T, Nakanishi H, Ohto-Nakanishi T, Akiyama T, Morita Y, Kishino Y, Okada M, Tani H, Soma Y, Nakajima K, Kanazawa H, Sugimoto M, Ko MSH, Suematsu M, Fukuda K (2020). Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells. iScience. 2020 Sep 6;23(9):101535. https://pubmed.ncbi.nlm.nih.gov/33083764/

162. Akiyama T, Sato S, Ko SBH, Sano O, Sato S, Saito M, Nagai H, Ko MSH, Iwata H (2020). Synthetic mRNA-based differentiation method enables early detection of Parkinson’s phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells. Stem Cells Transl Med. 2021 Apr;10(4):572-581. https://pubmed.ncbi.nlm.nih.gov/33342090/

163. Makino K, Shimizu-Hirota R, Goda N, Hashimoto M, Kawada I, Kashiwagi K, Hirota Y, Itoh H, Jinzaki M, Iwao Y, Ko M, Ko S, Takaishi H (2021). Unbiased, comprehensive analysis of Japanese health checkup data reveals a protective effect of light to moderate alcohol consumption on lung function. Sci Rep. 2021 Aug 5;11(1):15954. https://pubmed.ncbi.nlm.nih.gov/34354190/

164. Tanosaki S, Akiyama T, Kanaami S, Fujita J, Ko MSH, Fukuda K, Tohyama S (2022). Purification of cardiomyocytes and neurons derived from human pluripotent stem cells by inhibition of de novo fatty acid synthesis. STAR Protoc. 2022 Apr 28;3(2):101360. https://pubmed.ncbi.nlm.nih.gov/35516845/

*165. Amano T, Yu H, Amano M, Leyder E, Badiola M, Ray P, Kim J, Ko AC, Achour A, Weng NP, Kochba E, Levin Y, Ko MSH (2023). Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity. iScience. 2023 Mar 5;26(4):106335. https://pubmed.ncbi.nlm.nih.gov/36968065/

166. Kobori C, Takagi R, Yokomizo R, Yoshihara S, Mori M, Takahashi H, Javaregowda PK, Akiyama T, Ko MSH, Kishi K, Umezawa A (2023). Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3. Stem Cell Res Ther. 2023 Sep 8;14(1):242. https://pubmed.ncbi.nlm.nih.gov/37679843/

167. Choy C, Chen J, Li J, Gallagher DT, Lu J, Wu D, Zou A, Hemani H, Baptiste BA, Wichmann E, Yang Q, Ciffelo J, Yin R, McKelvy J, Melvin D, Wallace T, Dunn C, Nguyen C, Chia CW, Fan J, Ruffolo J, Zukley L, Shi G, Amano T, An Y, Meirelles O, Wu WW, Chou CK, Shen RF, Willis RA, Ko MSH, Liu YT, De S, Pierce BG, Ferrucci L, Egan J, Mariuzza R, Weng NP (2023). SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors. Nat Commun. 2023 Oct 23;14(1):6725. https://pubmed.ncbi.nlm.nih.gov/37872153/

168. Arora S, Yang J, Akiyama T, James DQ, Morrissey A, Blanda T, Badjatia N, Lai WKM, Ko MSH, Pugh BF, Mahony S (2023). Joint sequence & chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin. bioRxiv. 2023 Oct 31:2023.10.06.561228. https://pubmed.ncbi.nlm.nih.gov/37873361/

169. Koseki T, Teramachi M, Koga M, Ko MSH, Amano T, Yu H, Amano M, Leyder E, Badiola M, Ray P, Kim J, Ko AC, Achour A, Weng NP, Imai T, Yoshida H, Taniuchi S, Shintani A, Fujigaki H, Kondo M, Doi Y (2023). A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2. Vaccines (Basel). 11(12):1767. https://pubmed.ncbi.nlm.nih.gov/38140172/

*170. Akiyama T, Ishiguro KI, Chikazawa N, Ko SBH, Yukawa M, Ko MSH (2024). ZSCAN4-binding motif-TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes. DNA Res. 31(1):dsad029. https://pubmed.ncbi.nlm.nih.gov/38153767/

*171. Myers KC, Davies SM, Lutzko C, Wahle R, Grier DD, Aubert G, Norris K, Baird DM, Koga M, Ko AC, Amano T, Amano M, Yu H, Ko MSH (2025). Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells. NEJM Evid. 4(3):EVIDoa2400252. https://pubmed.ncbi.nlm.nih.gov/39998303/

172. Morita A, Ishii M, Asakura T, Yotsukura M, Hegab AE, Kusumoto T, Namkoong H, Ogawa T, Nakatake Y, Oda M, Saito F, Kamata H, Hamamoto J, Okamori S, Ebisudani T, Yasuda H, Sugimoto S, Kuze Y, Seki M, Suzuki Y, Hasegawa N, Asamura H, Watanabe H, Ko M, Sato T, Ieda M, Fukunaga K (2025). Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells. NPJ Regen Med. 10(1):30. https://pubmed.ncbi.nlm.nih.gov/40550799/

173. Kusumoto T, Yotsukura M, Asakura T, Namkoong H, Ogawa T, Hegab AE, Nakatake Y, Oda M, Saito F, Kamata H, Hamamoto J, Okamori S, Seki M, Suzuki Y, Hasegawa N, Asamura H, Watanabe H, Ko MSH, Ieda M, Fukunaga K, Ishii M (2025). Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice. Biochem Biophys Res Commun. 778:152384. https://pubmed.ncbi.nlm.nih.gov/40700809/

174. Akiyama T, Nakahara T, Sato S, Ishiguro KI, Yukawa M, Yamamoto M, Takahashi H, Ko MSH (2026). Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency. Development. 2026 Mar 30:dev.205328. https://pubmed.ncbi.nlm.nih.gov/41906541/




● Book Chapters

B1. Takano T, and Ko MSH. Enhancer sequences for gene expression regulation. In: Takano, T. (Ed.): Introduction to Genetic Engineering. Tokyo, Nanzan-Doh, Press, 1985, pp. 227-256 (in Japanese).

B2. Ko MSH. An equalized cDNA library and its application. Protein, nucleic acid and enzyme. 38: 420-428, 1993 (in Japanese).

B3. Ko MSH.: Strategy for the construction of an equalized cDNA library. In: Nojima, Y. (Ed.): Gene Libraries, Tokyo, Yoh-Do Sha, Press, 1994, pp. 135-144 (in Japanese).

B4. Ko M SH. Equalized cDNA libraries. In: Larrick, J.W., and Siebert, P.D. (Eds): Reverse Transcriptase PCR. London, Ellis Horwood, 1995, pp. 245-264.

B5. Kimber WL, Piao Y, Tanaka TS, Yoshikawa T, Hamatani T, Carter MG, and Ko MSH. Systematic Analysis of Mouse Preimplantation Development. In: Watson, A. (Ed): Mammalian Embryo Genomics: Biological Resource Management in Agriculture. Paris, OECD (Organization for Economic Co-Operation and Development), 2003, pp. 37-46.

B6. Tanaka TS, Carter MG, Aiba K, Jaradat SA, and Ko MSH. Genomic approaches to stem cell biology. In: Odorico, J.S., Pederson, R.A., and Zhang, S.U. (Eds): Human Pluripotent Stem Cells. New York, BIOS Scientific Publishers, Ltd, 2004, pp. 339-361.

B7. VanBuren V, and Ko MSH. Principles and Application of Embryogenomics. In: Meyers, R.A. (Ed.): Encyclopedia of Molecular Cell Biology and Molecular Medicine, 2nd Edition. Weinheim, WILEY-VCH, 2004, pp. 529-555.

B8. VanBuren V, and Ko MSH. Regulation of genome activity and genetic networks in mammals. In: Ruvinsky, A., and Graves, J.M. (Eds): Mammalian Genomics. Cambridge, CABI Publishing, 2004, pp. 201-220.

B9. Ko MSH (2008). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 17th Edition. (Eds. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J). McGraw-Hill, NY.

B10. Ko MSH (2011). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 18th Edition. (Eds. Longo DL, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Jameson JL, Loscalzo J). McGraw-Hill, NY.

B11. Ko MSH (2015). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 19th Edition. (Eds. Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J). McGraw Hill Professional, NY.