The University of Osaka · Biochemistry, Genetics and Molecular Biology
Professor Masataka Kikuchi's research lab focuses on unraveling the molecular and genetic mechanisms underlying neurodegenerative diseases, particularly Alzheimer's disease (AD), through integrative 'omics' approaches. The lab specializes in systems biology, analyzing protein interaction networks, gene expression profiles, and non-coding genetic variants to understand disease progression and identify key regulatory nodes. A central theme is the identification of disease subtypes and endophenotypes using advanced computational models, such as heterogeneous mixture learning, to improve early diagnosis and personalized prediction. The lab also investigates the polygenic architecture of AD across diverse populations, including non-European ancestries, to enhance the translational relevance of genetic risk scores.
Figures are computed from collected data and may differ slightly.
Our results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.
The molecular biological mechanisms of Alzheimer's disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed th
Alzheimer's disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested t
Mild cognitive impairment (MCI) is a high-risk condition for conversion to Alzheimer's disease (AD) dementia. However, individuals with MCI show heterogeneous patterns of pathology and conversion to AD dementia. Thus, detailed subtyping of MCI subjects and accurate prediction of the patients in whom MCI will convert to AD dementia is critical for identifying at-risk populations and the underlying biological features. To this end, we developed a model that simultaneously subtypes MCI subjects and
We showed that the AD PRS is useful in the Japanese population, whose genetic structure is different from that of the European population. These findings suggest that the polygenicity of AD is partially common across ethnic differences.
Eye movements are considered endophenotypes of schizophrenia. However, the genetic factors underlying eye movement are largely unknown. In this study, we explored the susceptibility loci for four eye movement scores: the scanpath length during the free viewing test (SPL), the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test (HPG), the duration of fixations during the far distractor paradigm of the fixation stability test (DF) and the integrated eye movement
Schizophrenia is a mental illness that involves both genetic and environmental factors. Clozapine, an atypical antipsychotic, is a well-established therapy for treatment-resistant schizophrenia. In this study, we focused on a set of monozygotic twins with treatment-resistant schizophrenia in which one twin effectively responded to clozapine treatment and the other did not. Our previous study generated neurons from induced pluripotent stem (iPS) cells derived from these patients and compared the
Abstract Background: Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer’s disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers.
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