Tokyo Women's Medical University

Graduate School of Medical Science

Human Pathology & Pathological Neuroscience

About us

In TWMU, Department of Pathology belongs to Faculty of Medicine, whereas “Human Pathology & Pathological Neuroscience” is a field of Graduate School of Medicine. The staff members in the former overlap those in the latter. In the Faculty of Medicine, we take part of medical student education from the view point of active learning of morphological alterations reflecting pathophysiological mechanisms of several organ diseases. In Graduate School of Medicine, we work on pathological studies to determine molecular processes of a subset of diseases and search molecular targets specific for certain disorders, by epigenomic, genomic, transcriptomic, proteomic, and metabolomic analyses, using human tissues, disease model animals, and disease model cell cultures. Characteristically, our research is every time based on human diseases unlike other departments. The major topics of research in our colleagues are malignant glioma, amyotrophic lateral sclerosis, Fukuyama congenital muscular dystrophy, autoimmune nervous system disorder, cerebral ischemia, atherosclerosis, carcinoma metastasis, and thyroid carcinoma. Some of them are our original studies, and others are collaborative studies together with other departments or institutes.

Research

(1)Elucidation of the nature of atherosclerosis
Atherosclerotic arterial occlusion, which leads to myocardial infarction and cerebral infarction, is the leading cause of death in developed countries, comparable to cancer in general. Plaque instability, the main cause of such arterial occlusion, is characterized by an increased lipid core and thinning of the fibrous capsule, but it is not known why this occurs. Smooth muscle, the main component of the fibrous capsule, has been thought to be uniformly dedifferentiated, but we have found that the degree of differentiation of smooth muscle varies, and that it is more dedifferentiated when plaques become unstable. In the future, we would like to elucidate whether this smooth muscle dedifferentiation is the cause of plaque destabilization or whether it interacts with the lipid core, and contribute to the prevention, diagnosis, and treatment of plaque destabilization.

(2) Induction of differentiation of pluripotent stem cell-derived immature teratomas
The goal of inducing differentiation of pluripotent stem cells such as ES cells and iPS cells to form transplantable tissues and organs currently remains a cellular-level result. On the other hand, immature teratomas formed by transplanting pluripotent stem cells into immunodeficient mice are malignant tumors and have not received much attention for transplantation. We have found that these immature teratomas transform into differentiated mature teratomas after intraperitoneal administration of anticancer agents to the teratoma-bearing host. In the future, we would like to refine this technique and explore ways to induce differentiation into desired tissues and organs.

(3)Cancer metabolism in malignant brain tumor
Cancer cells depend on metabolic reprogramming to drive nucleotide, lipid, and protein synthesis needed for survival. Of interest, recent molecular genetic studies revealed discrete links between oncogenotypes and the resultant metabolic phenotypes. Further, more comprehensive approaches are applied to unravel the dynamic spatio-temporal regulatory map of metabolites that enable cancer cells to adapt to their microenvironment to maximize tumor growth. Our approach for the elucidation of cancer biology is to leverage “OMICS” approaches to link cancer cell genotype, epigenotype and phenotype through metabolic reprogramming for improving the management of patients with malignant brain tumor, glioblastoma.

(4)Abnormal protein aggregates of in neurodegeneration
Most neurodegenerative diseases are characterized by deposition of abnormal protein aggregates with amyloid-like structures, but the link between toxic protein aggregates and neuronal cell death remains unclear. Abnormalities in signaling cascades of programmed cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagic cell death as well as unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. We would like to clarify how abnormal protein accumulation would induce cell death by virally introducing disease-related genes into cultured neuron and glia, which will lead to novel therapeutics against neurodegenerative disorders.

(5)Fukutin and human diseases
Fukutin, a product of the causative gene of Fukuyama congenital muscular dystrophy (FCMD), is known to be responsible for basement membrane formation. Patients with FCMD exhibit not only muscular dystrophy but also central nervous system abnormalities, including polymicrogyria and neurofibrillary tangles (NFTs) in the cerebral cortex. We have so far clarified novel roles of fukutin in the proliferation, differentiation and degeneration of neurons and glia. Our research aim is to further unravel other proposed functions of fukutin that have not been fully understood yet.

(6)Metastatic capacity of thyroid cancer cells
Among thyroid cancers, papillary carcinoma tends to metastasize via lymphatics whereas follicular carcinoma prefers hematogenous routes. It has not been clarified yet what makes their difference in metastatic capacity. Our research focus is to morphologically and quantitatively analyze the mechanism underling the metastatic difference between papillary and follicular carcinoma cells with the use of thyroid cancer cell lines and human surgical specimens.

Faculty

Kurata Atsushi (Professor and Head) taking charge of (1) (2)
Tomoko Yamamoto (Associate Professor) taking charge of (5)
Kenta Masui (Associate Professor) taking charge of (3)
Yoichiro Kato (Assistant Professor) taking charge of (4) (6)

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