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開催日時: 2016年11月24日 17:00 ~ 18:00
開催場所: 2号館 小講義室 
講師: 杉井 重紀
所属: Group Leader, Singapore Bioimaging Consortium (SBIC), A*STAR Assistant Professor, Duke-NUS Medical School

演題: Adipose-derived Stem Cells: Potential for Metabolic Reprogramming

Adipose tissue is an expandable and readily attainable source of proliferating, multipotent adipose-derived stem cells (ASCs), holding great therapeutic potentials. However, more work is necessary to fully understand biological properties of ASCs and explore translational approaches by using or targeting ASCs. By comprehensive image-based high content screening, we identified novel fat-depot specific cell surface markers, CD10 and CD200, which can predict how well ASCs can differentiate into mature functional adipocytes. Through another study on whole genome-wide gene expression analyses, we identified novel pathways of retinoid metabolism and oxidative stress. High level of retinoic acid negatively affects early stage of adipogenic differentiation of ASCs, which can be reversed by antagonism of retinoic acid receptors. Similarly it was found that high oxidative stress associated with ageing or visceral obesity affects ASC’s ability for differentiation, proliferation, migration and/or senescence. Treatment with anti-oxidants was found to be effective in reducing reactive oxygen species and improving these ASC properties. Collectively, these results suggest that stem cells can be the cellular target for improving quality of fat tissue and adipocytes through use of specific cell surface markers, modulating RA pathway, or reversal of oxidative stress. These molecular markers and factors may be useful for future metabolic reprogramming studies in different approaches: bioimaging, screening for improved adipocyte development, or reprogramming into induced pluripotent stem (iPS) cells.

世話人: ○渡辺 すみ子(再生基礎医科学)
 谷 憲三朗(ALA先端医療学社会連携研究部門)
開催日時: 2016年10月12日 14:00 ~ 15:00
開催場所: 総合研究棟 2階会議室
講師: 小沢 学
所属: 東京大学医科学研究所
システム疾患モデル研究センター 発生工学研究分野・助教
演題: 持続的精子形成を制御するヒストンメチル化修飾の役割


世話人: ○吉田 進昭(発生工学研究分野)
中江 進(システムズバイオロジー研究分野)
開催日時: 2016年10月12日 14:00 ~ 15:30
開催場所: 病院A棟8階南会議室
講師: 1. Robert Andtbacka, MD, CM, FACS, FRCSC
2. André Choulika, Ph.D.
所属: 1. Associate Professor, Department of Surgery, University of Utah Huntsman Cancer Institute
2. Chairman of the Board of Directors and Chief Executive Officer, Cellectis
演題: 1部 Oncolytic Viral Therapy -Changing the Paradigm of Cancer Treatment
2部 Enhancing the Power of Allogeneic CAR T-Cells by Gene Editing

1部 Oncolytic viruses (OVs) are rapidly changing the treatment of advanced metastatic melanoma and other cancers. These therapies are directly injected into dermal, subcutaneous and lymph node metastases where they are preferentially taken up by metastatic tumor cells. Once inside tumor cells, viral replication leads to tumor cell lysis, exposure of tumor associated antigens to the immune system and activation of the adaptive immune system resulting in effects on distant uninjected tumors as well. To date, several different viral therapies (T-VEC, HF10 and CAVATAK etc.) have been developed and evaluated in patients with metastatic cancers. Many of these therapies have been shown to have robust effects on injected and distant uninjected lesions. OVs have also been shown to modify the tumor microenvironment by increasing tumor infiltrating lymphocytes resulting in a “priming” of the immune system with an improved response to other immunotherapies, such as checkpoint inhibitors. The treatments have generally been well tolerated and responses have often been durable.

2部 Adoptive immunotherapy using engineered immune cells has emerged as a powerful approach to treat cancer. The potential of this approach relies on the ability to redirect the specificity of immune cells through ex vivo genetic engineering and transfer of chimeric antigen receptors (CARs) or engineered TCRs. Cellectis proprietary nuclease-based gene editing technologies, combined with 16 years of gene editing experience, makes it possible to efficiently edit any gene in primary cells with very high precision and therefore offers unparalleled possibilities to design the next generation of immunotherapy products.
We will describe how the TALEN® gene-editing technology allows creating allogeneic CAR T-cells (derived from healthy donors rather than from patients themselves) but also empowering cells with additional safety and efficacy attributes. These new features include, among other possibilities, control properties designed to prevent engineered cells from attacking healthy tissues, to prevent auto-destruction, and to enable these cells to tolerate standard oncology treatments.

世話人: ○小澤 敬也(病院長、遺伝子治療開発分野・教授)
 玉田 耕治(遺伝子・細胞治療センター・教授(委嘱))
開催日時: 2016年10月12日 15:30~17:00
開催場所: 4号館3階 国際粘膜ワクチン開発研究センター
講師: 齋藤 伸一郎
所属: 東京大学医科学研究所 感染遺伝学分野 助教
演題: Toll-like receptor 7によるIFN-α産生機構と代謝機構の関係

形質細胞様樹状細胞(pDC)は、ウイルスのRNA成分をToll-like receptor (TLR)7を介して認識し、1型インターフェロン(IFN-)を大量に産生することでウイルスに対する防御に関わる。しかし、IFN-の産生の機構は殆んどわかっていない。我々は、液体クロマトグラフィー質量分析法にてTLR7に会合する分子を同定した。その分子は、ライソソーム上に局在する低分子量G蛋白質Arl8bであった。Arl8bはライソソームを中心体から外側に輸送するのに関わっている分子である。本発表ではTLR7の活性化に伴う微小管上での移動が、IFN-の産生誘導と結びつくこと、そしてそこには代謝に関わるmTorC1が存在していることについて紹介する。さらにArl8bと関連する分子による免疫調節の機構についても紹介する。

世話人: ○三宅 健介 (感染遺伝学分野)
 川口 寧 (ウイルス病態制御分野)
開催日時: 2016年10月26日 16:00 ~ 17:00
開催場所: 4号館3階 国際粘膜ワクチン開発研究センター会議室
講師: James DI SANTO, Ph.D
所属: Institut Pasteur・教授
演題: Innate Lymphoid Cells: Novel Effectors of Immune Defense and Tissue Homeostasis

Innate lymphoid cells (ILC) are a newly described family of hematopoietic cells that lack antigen-specific receptors but can be activated to promptly produce large amounts of cytokines (including interleukin (IL)-5, -13, -17A, -22, TNF- and interferon-γ) and thereby contribute to the immediate, first-line immune defense against viral, bacterial, and parasitic infections. ILCs include the previously described natural killer (NK) cells and have a similar 'natural' effector function which is immediately available during immune responses and prior to that of adaptive immunity. Three groups of ILC (ILC1, ILC2, ILC3) have been described that share biological activities of T helper (Th)1, Th2 and Th17/22 subsets and CTL. ILCs are active during both fetal and adult life and play important roles in the homeostasis of mucosal and non-mucosal tissues. How ILCs develop from hematopoietic precursors is poorly defined and how ILCs are integrated into ongoing immune responses remains unclear. Knowledge in this arena is a prerequisite for harnessing the clinical potential of these potent immune effector cells. My laboratory investigates the critical control points that regulate ILCs differentiation and plasticity. Using complementary approaches, we hope to shed new light on the biological determinants which condition ILC reactivity in mice and man. Understanding how the threshold of ILC responsiveness is set prior to and during immune responses may have important implications for disease intervention.

世話人: ○植松 智(自然免疫制御分野)
 清野 宏(炎症免疫学分野)
開催日時: 2016年10月12日 14:00 ~ 15:30
開催場所: 4号館3階 国際粘膜ワクチン開発研究センター
講師: 倉島 洋介
所属: 東京大学医科学研究所 炎症免疫学分野 助教
演題: マスト細胞の機能研究から明らかとなってきたアレルギー・炎症治療の新展開


世話人: ○三宅 健介 (感染遺伝学分野)
 川口 寧 (ウイルス病態制御分野)
開催日時: 2016年9月15日 18:00~19:00
開催場所: 2号館 大講義室
講師: 櫛 山 暁 史
所属: 公益財団法人 朝日生命成人病研究所・医長
演題: Linking dietary fat, microbiota, innate immunity and lifestyle-relate diseases by resistin like molecule β

Resistin like molecule  (RELM) reportedly possesses the multiple functions including local immune response and regulation of microbiota. We revealed that not only mucus secreting epithelial cells but also macrophages in the atherosclerotic tissue and Kupffer cells in the liver express RELM High fat diet or saturated FFA increases RELMβ expression in both cells. Circulating RELMβ suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet.
Both RELM expression levels in the colon and the numbers of RELM-positive Kupffer cells were markedly increased in mice liver by methionine-choline deficient diet (MCD) feeding and in human liver of the patients with NASH. Furthermore, RELM mice were highly resistant to atherosclerosis in ApoEKO mice and the MCD-induced NASH. RELM regulated the intestinal environment, such as gut permeability measured by LPS absorption and microbiota. RELM directly enhanced immune responses of the macrophages, thus RELMKO macrophages showed less lipid accumulation and lower responsibility for LPS than control macrophages. The radiation chimeras between the wild-type and RELM KO mice revealed the requirement of both non-hematopoietic and hematopoietic cell-derived RELM for full manifestation of NASH. Increased RELM in the gut might contribute to the impaired barrier function of the colon and its resultant increased LPS absorption from the gut, while Kupffer cell-derived RELM to the high responsibility for LPS-induced inflammatory response in the liver.
We hypothesize that dietary saturated fatty acids induce RELMβ expression, signaling the necessity for inflammation into the systemic macrophages including remote foam cells and Kupffer cells, leading to chronic inflammation of lifestyle-related diseases.
1. Okubo H et al. Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice. Sci Rep. 2016 Jan 28;6:20157. doi: 10.1038/srep20157.
2. Kushiyama A et al. Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development. Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1986-93. doi:10.1161/ATVBAHA.113.301546.
3. Kushiyama A et al. Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet. J Biol Chem. 2005 Dec 23;280(51):42016-25.

世話人: ○田中 廣壽(抗体・ワクチンセンター 免疫病治療学分野 教授)
 細野 治 (アレルギー免疫科 准教授)
開催日時: 2016年9月13日 15:00 ~ 17:00
開催場所: 病院A棟 8階北(大)会議室
講師: 1.Prof. Itamar Grotto
2.Prof. Abraham (Avi)Israeli
所属: 1.Associate Director General of Israel's Ministry of Health
2.Chief Scientist of Israel's Ministry of Health
演題: The Israel Health System: from Innovation to Improved Health

The health care system in Israel is a unique system, in which all residents have basic health insurance within one of 4 HMO's. In addition, all clinical data is digital. This allows having access to one's personal health information for decades, which then can be used for the development of new diagnosis, better treatment and the development of new innovative developments for improving the health care in Israel as well as for all human kind. Hence, the Israeli health system not only treats patients, but by utilizing big data tools, nano-technology, system medicine, etc. allow improved innovative patient care.
Prof. Itamar Grotto (Associate Director General of Israel's Ministry of Health) will briefly describe the Israeli health care system, with emphasize on issues that we believe are interesting to academic and professional audience. For example: quality indicator measurements within the community and the hospitals; patient centered care etc.
Prof. Abraham (Avi)Israeli (Chief Scientist of Israel's Ministry of Health) will speak about some innovations that stem from our health care system. This will include some innovations in regard to clinical trials utilizing stem cells; issues concerning bio-banking.

世話人: ○小澤 敬也(病院長、遺伝子治療開発分野・教授)
 東條 有伸(分子療法分野・教授)
開催日時: 2016年9月23日 15:00 ~ 16:00
開催場所: 2号館 大会議室
講師: Seth Blackshaw 
所属: Professor
Department of Neuroscience Johns Hopkins University School of Medicine
演題: Transcriptional regulatory networks controlling retinal development

The mammalian retina is an ideal system for studying how cell types of the central nervous system are formed. My group uses genome-wide approaches to comprehensively identify the transcriptional regulatory networks that control neuronal and glial cell fate in the developing retina. I will describe our recent work on identification of transcription factors that control developmental changes in retinal progenitor competence, that control the balance of retinal neurogenesis and gliogenesis, and that control the differentiation and function of retinal glia.

世話人: ○渡辺 すみ子(再生基礎医科学)
 大津 真(ステムセルバンク)
開催日時: 2016年10月3日 17:30 ~ 18:30
開催場所: 病院8階北(大)会議室 
講師: 中村 能久
所属: シンシナティ小児病院医療センター・准教授
演題: Role of dsRNA pathways and miRNA-reguatory machinery in obesity

A broad array of inflammatory and stress responses is frequently evoked in insulin-targeted metabolic tissues during the pathogenesis of obesity. This atypical state engages immune response pathways, including activation of a variety of stress kinases, elevated production of an array of immune mediators, and recruitment of immune cells into metabolic tissues, which negatively impact nutrient metabolism and glucose metabolism. However, the molecular basis for the induction of metabolic inflammation and the vast network of pathological responses in obesity remains elusive. Recent evidence indicates that metabolic inflammation results from deregulated double-stranded RNA (dsRNA) processing/signaling in metabolic tissues, which adversely regulates systemic glucose metabolism in obesity. These findings suggest the involvement of altered RNA networks in the immunometabolic regulation of obesity. This presentation will focus on the regulation of endogenous dsRNA and microRNA-mediated events and how their functional changes are associated with inflammatory responses and metabolic deterioration in obesity.

世話人: ○井上 純一郎 (分子発癌分野)
 山梨 裕司 (癌細胞増殖部門)