A5010814235- RNA and protein synthesis mechanisms
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Redox biology and oxidative stress
- Neurogenetic and Muscular Disorders Research
- Multiple Myeloma Research and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Pregnancy and preeclampsia studies
- Glutathione Transferases and Polymorphisms
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Trace Elements in Health
- Nerve injury and regeneration
- Cellular transport and secretion
- Lysosomal Storage Disorders Research
- Cancer-related gene regulation
- Protein purification and stability
- Toxin Mechanisms and Immunotoxins
The University of Tokyo
2012-2024
Tokyo Medical and Dental University
2024
Ludwig Cancer Research
2016-2018
University of Oxford
2016-2018
Theodore Roosevelt High School
2017
National Mie Hospital
2015
Niigata University
1972-1979
Saint Louis University
1975
The Cancer Institute Hospital
1968
Analysis of ALS patient iPSC-derived motor neurons indicates that Src/c-Abl inhibitors may have potential for treating ALS.
Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo extra-terminal) inhibitors their significant activity in diverse tumor models rapidly translated into clinical studies motivated drug efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture BRD protein complexes complicates predictions consequences pharmacological targeting. To address this issue, we developed a promiscuous inhibitor...
Elucidation of interactions involving DNA and histone post-translational-modifications (PTMs) is essential for providing insights into complex biological functions. Reader assemblies connected by flexible linkages facilitate avidity increase affinity; however, little known about the contribution to recognition process multiple PTMs because rigidity in absence conformational flexibility. Here, we resolve crystal structure triple reader module (PHD-BRD-PWWP) ZMYND8, which forms a stable unit...
Abstract Objective: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that characterized by the selective loss of upper and lower motoneurons. Although >100 different Cu, Zn superoxide dismutase ( SOD1 ) mutations have been identified in ALS patients, it remains controversial whether all them are disease‐causative mutations. Therefore, necessary to develop molecular mechanism‐based diagnosis treatment caused Methods: We previously reported 3 pathogenic cause chronic...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure. To develop effective treatments for this devastating disease, an appropriate strategy targeting the molecule responsible pathogenesis of ALS needed. We previously reported that mutant SOD1 protein causes motor neuron death through activation ASK1, mitogen-activated kinase kinase. Additionally, we recently developed K811 and K812, which are selective inhibitors ASK1. Here, report effect K812 in mouse model...
Endoplasmic reticulum (ER) proteostasis is maintained by various catabolic pathways. Lysosomes clear entire ER portions ER-phagy, while proteasomes selectively misfolded or surplus aberrant proteins ER-associated degradation (ERAD). Recently, lysosomes have also been implicated in the selective clearance of proteins, but molecular basis remains unclear. Here, we show that phosphatidylinositol-3-phosphate (PI3P)-binding protein TOLLIP promotes lysosomal membrane including an artificial...
Cellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening oncogene activation, induce by damaging nuclear DNA. However, the mechanisms linking DNA damage to remain unclear. Here, we show that response (DDR) signaling mitochondria triggers senescence. A genome-wide small interfering RNA screen implicated outer mitochondrial transmembrane protein BNIP3 induction. We found phosphorylated DDR kinase...
Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder. Despite its severity, there are no effective treatments because of the complexity pathogenesis. As one underlying mechanisms Cu, Zn superoxide dismutase ( SOD1 ) gene mutation-induced ALS, mutants (SOD1 mut commonly interact with an endoplasmic reticulum-resident membrane protein Derlin-1, triggering motoneuron death. However, importance SOD1-Derlin-1 interaction in vitro human model and vivo mouse...
High salt conditions and subsequent hyperosmolarity are injurious cellular stresses that can activate immune signaling. Nuclear factor of activated T-cells 5 (NFAT5) is an essential transcription induces osmoprotective genes such as aldose reductase (AR) betaine-GABA transporter 1 (BGT1). stress-mediated NFAT5 activation also reported to accelerate the inflammatory response autoimmune diseases. However, systemic regulation remains unclear. Here, we performed a genome-wide siRNA screen...
Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), resides in the mitochondria regulates many biological processes, including cell death, mitophagy, immune responses. Because BAT mitochondria-rich tissue, we have hypothesized PGAM5 has physiological function BAT. We previously reported PGAM5-knockout (KO) mice are resistant...
Employing livers from rats fed on a protein-free diet for two weeks, the effects of protein deficiency both biosynthesis and degradation rRNA were investigated following results obtained. 1. Protein led to decrease total liver RNA content per DNA about 80% that in normal rat liver. 2. From kinetics labelling with [14C]orotic acid vivo, half-lives cytoplasmic rRNA's protein-deficient determined be 6.2 5.1 days, respectively. Furthermore, considering pool size liver, turnover rate was...
Mutations within Superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS), accounting for approximately 20% of familial cases. The pathological feature is a loss motor neurons with enhanced formation intracellular misfolded SOD1. Homozygous SOD1-D90A in ALS has been reported to show slow disease progression. Here, we rare case slowly progressive patient harboring novel SOD1 homozygous mutation D92G (homD92G). neuronal cell line overexpressing SOD1-D92G showed lower ratio the...