信大医学部医学科研究紹介2019（英語版）

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11Let’s hunt disease-causing genes!For the happiness of patients and families!Summary of ActivityWe conduct genetic investigation on human genetic / congenital disorders, in collaboration with Center for Medical Genetics, Shinshu University Hospital. The main theme is to “hunt disease-causing genses” through careful clinical assess-ment and advanced genetic analyses including next-generation sequencing. Together with clinical studies on these disorders, we aim to make a contribution to establish a society where these patients can live healthy and happy lives.・ Comprehensive study of hereditary connective tissue disorders, especially Ehlers-Danlos Syndrome Kosho type (musculocontractural EDS-CHST14)・ Genetic investigation for intellectual disabilities (ID), autism spectrum disorders (ASD), and epilepsy・ Molecular cytogenetic investigation including microarray and FISHThe best part of clinical genetics is to establish a new disease entity from only one patient. To find the disease-causing gene could be a breakthrough in understanding the pathophys-iology of the disease, developing innovative therapies, and uncovering relevant biological bases.After obtaining a medical specialist such as a pediatrician, you can enter our “clinical genetics” course where you have sufficient training for clinical, cytogenetic, and molecular genetics to obtain a certified clinical geneticist.Research subjectOutlook for researchOutlook for students after graduationMedical Genetics（Chief: Prof. Tomoki Kosho）“We encountered a patient with characteristic facial features, multiple congenital contractures, and large subcutaneous hematoma (Kosho et al., 2005; 2010)Isolation of CHST14Defective activities of D4ST1Defect of dermatansulfateInsufficient assembly of collagen fibrilsEstablishment of Musculocontractural Ehlers-Danlos Syndrome, (Kosho type) !“Referral of patients with ID“Target resequencingof ID-related genes”“Whole exomesequencingNext-generation-based approaches-tients with ID in Japan ! “Uncovering molecular pathology of 4p-syndrome(Shimizu et al, 2013)“Cytogenetic investigation”Classical to advanced approaches !Searching a key for suppressing cancer metastasisSummary of ActivityOur efforts are directed to reveal molecular mechanisms of tumorigenesis and tumor metastasis. By using tumor-bearing mouse model system, we have de-termined that primary tumor elicits an inflammatory reaction in a remote organ before metastasis, which is termed as “premetastatic soil”. This inflammatory reaction enhances vascular permeability, and recruitment of immunosuppressor cells and/or circulating tumor cells, these factors increase the risk of tumor me-tastasis. Thus, we consider that controlling the premetastatic phase is an import-ant step to prevent tumor metastasis.・Investigation of a mechanism of the carcinogenesis・Elucidation of cancer metastasis・Functional analysis of anti-metastatic cellsToday, in a cancer therapy, especially against metastatic cancer, anticancer drug treatment was employed. Our mouse study revealed that a subtype of innate immune cells have an-ti-metastatic abilities. These cells cancel the premetastatic soil formation and attack against metastatic cells. We are considering clinical application based on our research data.Through the cancer study, you can extend your views of various fields. It will give you great activity in many kinds of area, such as healthcare, education, public administration, research, and so on.Research subjectOutlook for researchOutlook for students after graduationBiochemistry and Molecular Biology（Chief: Prof. Sachie Hiratsuka）Pre-metastatic permeability controlled by innate immune system. Initially, tumor-de-rived CCL2 stimulates CCR2 in the pre-metastatic lungs. Next, this induces S100A8-SAA3 pathway and stimulates TLR4/MD2 cycles. Those cascades further promote Detection of the focal region in tumor-bearing mice with the permeability phenomena. LLC and E0771, breast cancer cells lines, were used to generate tumor-bearing mice. Note that some hyper-permeability area made by Evans Blue dye injection, was found in tumor-bearing mouse lung.