Ryunosuke Saiki
A5036420001- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer and Skin Lesions
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- COVID-19 Clinical Research Studies
- Lymphoma Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- SARS-CoV-2 and COVID-19 Research
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- Infectious Diseases and Mycology
- Blood disorders and treatments
- Polyamine Metabolism and Applications
- Epigenetics and DNA Methylation
- Multiple Myeloma Research and Treatments
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Nonmelanoma Skin Cancer Studies
- Acute Lymphoblastic Leukemia research
Kyoto University
2016-2025
Mie University
2024-2025
Matsumoto University
2023
Abstract Germ line DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features DDX41-mutated MNs remain to be elucidated. Here we performed a comprehensive characterization MNs, enrolling total 346 patients with pathogenic/likely-pathogenic (P/LP) germ and/or somatic mutations from 9082 MN patients, together 525 first-degree relatives and wild-type (WT) patients. P/LP explained ∼80% known predisposition...
Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated development1-3. However, our knowledge is still missing with regard to what additional driver events take place order, before one or more these tissues ultimately evolve cancer. Here, using phylogenetic analyses multiple microdissected samples from both and non-cancer lesions, we show unique evolutionary histories breast cancers harbouring der(1;16),...
STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant comutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show critical role an interplay between RUNX1 regulation enhancer-promoter looping transcription hematopoiesis. Combined loss RUNX1, which colocalize at enhancer-rich, CTCF-deficient sites, synergistically attenuates loops,...
Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of in cohort Japanese individuals collected during initial waves pandemic, with 3,289 unaffected controls. We identified variant on chromosome 5 at 5q35 (rs60200309-A), close to dedicator cytokinesis 2 gene (DOCK2), which was associated patients less than 65 years age. This risk allele prevalent East Asian but rare...
Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 disease 2019 (COVID-19) patients 75 healthy controls Japanese ancestry with host genetic data. COVID-19 showed a low fraction nonclassical monocytes (ncMono). report downregulated transitions classical to ncMono reduced CXCL10 expression...
Aberrant immune responses to viral pathogens contribute pathogenesis, but our understanding of pathological caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019...
Studying the genetic regulation of protein expression (through quantitative trait loci (pQTLs)) offers a deeper understanding regulatory variants uncharacterized by mRNA (expression QTLs (eQTLs)) studies. Here we report cis-eQTL and cis-pQTL statistical fine-mapping from 1,405 genotyped samples with blood 2,932 plasma expression, as part Japan COVID-19 Task Force (JCTF). Fine-mapped eQTLs (n = 3,464) were enriched for 932 validated massively parallel reporter assay. pQTLs 582) missense...
Extramammary Paget disease (EMPD) is an uncommon skin malignancy whose genetic alterations are poorly characterized. Previous reports identified mutations in chromatin remodeling genes and PIK3CA. In order to unambiguously determine driver EMPD, we analyzed 87 EMPD samples using exome sequencing combination with targeted sequencing.First, 37 that were surgically resected whole-exome sequencing. Based on several silico analysis, built a custom capture panel of putative 50 additional...
Abstract Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious that has caused millions of deaths, where comprehensive understanding mechanisms still unestablished. In particular, studies gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on thorough analysis whole blood RNA-seq data from 465 genotyped samples the Japan Task Force, including 359 severe 106 non-severe cases. We discover 1169 putative causal...
Several X-linked genes escape from X chromosome inactivation (XCI), while differences in across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression the inactivated with droplet-based single-cell RNA sequencing (scRNA-seq) data. The differentially expressed analyses large-scale blood scRNA-seq datasets consistently identified stronger lymphocytes than myeloid cells. An extension of to a 10x multiome dataset...
Germline loss of function (LoF) DDX41 variants predispose to late-onset hematopoietic malignancies (HMs), predominantly myeloid lineage. Among 43 families with germline LoF variants, bone marrow (BM) biopsies in those without (n=8) or (n=21) revealed mild dysplasia peripheral blood (57%) and BM (88%), long before the average age DDX41-related HM onset. Therefore, we recommend baseline people DDX41LoF alleles avoid over-diagnosis myelodysplastic syndromes. A variety solid tumors were also...
Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 537 BNT162b2 vaccinees Japanese ancestry. are associated with heavy chain (IGH) major histocompatibility complex (MHC) locus, MHC. The lead variants at IGH contain population-specific missense variant (rs1043109-C; p.Leu192Val) constant gamma 1...
Background and Clinical Significance: Nephrotic syndrome predisposes patients to venous thromboembolism. This case highlights the challenges of diagnosing pulmonary embolism in nephrotic with renal dysfunction, emphasizes utility ventilation–perfusion lung scintigraphy when contrast is contraindicated. Case Presentation: A 52-year-old male presented fatigue, left back pain, dyspnea, lower limb edema. The laboratory findings indicated significant proteinuria, hypoalbuminemia, impaired...
Abstract Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid characterized by prominent proliferation whose molecular basis poorly understood. To elucidate the underlying mechanism proliferation, we analyzed 121 AEL using whole-genome, whole-exome, and/or targeted-capture sequencing, together with transcriptome analysis 21 samples. Combining publicly available sequencing data, found high frequency gains and amplifications involving EPOR/JAK2 in TP53-mutated cases,...
Abstract To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in face current devastating pandemic. Here, we report a genome-wide association study (GWAS) COVID-19 Japanese population led by Japan Task Force, as one initial discovery GWAS studies performed on non-European population. Enrolling total 2,393 cases and 3,289 controls, not only replicated previously reported risk variants (e.g., LZTFL1, FOXP4,...
Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events acute myeloid leukemia (AML) as well preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 infrequent AML, but the level expression HSCs has been found to decline with age. We examined impact gradual decrease TET function AML development by generating mice Tet deficiency at various degrees. Tet2f/f and Tet3f/f were crossed expressing Mx1-Cre generate Tet2f/wtTet3f/fMx-Cre+...