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)Clinicopathological study of pulmonary hemangiomas and search for their molecular biological basis
Hemangiomas of the lung have been considered rare; since we report the clinicopathologic features of SPCH in 2016 at first, similar reports with larger number of cases have been published, especially in East Asia. However, the epidemiology and molecular pathology of SPCH have not been fully analyzed. We are now conducting a Sanger sequence to confirm the genetic mutations and to elucidate the pathogenesis mechanism of the disease, targeting the genetic mutations frequently observed in hemangiomas in other organs.

(4)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.

(5)Abnormal aggregation process of amyloid β (Aβ) and its clearance mechanism in Alzheimer’s disease (AD)
The pathological change of AD is characterized by senile plaques (deposition of Aβ outside of neurons) and neurofibrillary tangles (intracellular aggregates of hyperphosphorylated tau protein), followed by massive neuronal loss. Based on several genetic and pathological studies, the widely accepted amyloid hypothesis postulates that Aβ accumulation in the brain is the trigger of a pathological cascade leading to AD. We aim to elucidate the abnormal aggregation process of Aβ by characterization of seed Aβ species that initiate and expand β-amyloidosis in vivo and by identification of anatomical clearance pathways of Aβ using autopsied brain samples. These approaches might provide new therapeutic strategy for AD.

(6)Metastatic capacity of thyroid cancer cells
In thyroid cancer, two point mutations in the promoter region of the TERT gene (C228T and C250T) are well known. Additionally, a single nucleotide polymorphism (rSNP) called rs2853669 is known to exist downstream of these mutations. Previous studies in other tumors have reported that the presence of rs2853669 is associated with increased expression of TERT mRNA. In a previous study of 58 cases of papillary thyroid carcinoma, we found a significant correlation between the presence of rs2853669 and tumor size. However, the underlying mechanism remains unclear. In this study, we aim to explore candidate factors involved in tumor size enlargement and investigate their molecular functions.

Faculty

Kurata Atsushi (Professor and Head) taking charge of (1) (2)
Hirotsugu Hashimoto (Associate Professor) taking charge of (3)
Tomoko Yamamoto (Associate Professor) taking charge of (4)
Mayu Hakozaki (Assistant Professor) taking charge of (5)
Yuu Arimasu (Assistant Professor) taking charge of (6)

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