◇ 2025年9月24日（水）加齢研セミナーのご案内
| 日時： | 2025年9月24日（水）10時～ Wednesday, 24 September 2025, 10:00～ |
| 場所： | 加齢医学研究所 実験研究棟7階 セミナー室１ 7th Floor, Seminar Room 1, IDAC Center for Basic Aging Research |
| 演題： | Identification of Druggable and Redox Vulnerabilities in Cancer |
| 講師： | Dr.Liron Bar-peled |
| 所属： | The Center for Cancer Research at Massachusetts General Hospital, The Department of Medicine at Harvard Medical School |
| 担当： | 河岡 慎平（生体情報解析分野・内線8568） Kawaoka Shinpei (Dept. Integrative Bioanalytics, ext.8568) |
| 連絡先： | 河岡 慎平（生体情報解析分野・内線8568） Kawaoka Shinpei (Dept. Integrative Bioanalytics, ext.8568) |
| 要旨： | Reactive oxygen species (ROS) underlie human pathologies including cancer and neurodegeneration. However, the proteins which sense ROS levels and regulate their production through their cysteines remain ill defined. Systematic base-editor and computational screens revealed cysteines in VPS35–a Retromer trafficking complex member, when mutated phenocopy inhibition of mitochondrial translation. We find that VPS35 underlies a reactive metabolite-sensing pathway that lowers mitochondrial translation to decrease ROS levels. Intracellular H2O2 oxidizes cysteines within VPS35, resulting in Retromer dissociation from endosomal membranes and subsequent plasma membrane remodeling. We demonstrate that plasma membrane localization of Retromer substrate SLC7A1 is required to sustain mitochondrial translation. Furthermore, lowering VPS35 levels or oxidation of its ROS-sensing cysteines confers resistance to ROS-generating chemotherapies including cisplatin in ovarian cancer models. Thus, we identify that intracellular ROS levels are communicated to the plasma membrane through VPS35 to regulate mitochondrial translation, connecting cytosolic ROS sensing to mitochondrial ROS production. |
| 日時： | 2025年9月24日（水）11時～ Wednesday, 24 September 2025, 11:00～ |
| 場所： | 加齢医学研究所 実験研究棟7階 セミナー室１ 7th Floor, Seminar Room 1, IDAC Center for Basic Aging Research |
| 演題： | Iron-Dependent Redox Control of Adipose Remodeling in Cancer |
| 講師： | Dr.Christine Chio |
| 所属： | Columbia University Irving Medical Center |
| 担当： | 河岡 慎平（生体情報解析分野・内線8568） Kawaoka Shinpei (Dept. Integrative Bioanalytics, ext.8568) |
| 連絡先： | 河岡 慎平（生体情報解析分野・内線8568） Kawaoka Shinpei (Dept. Integrative Bioanalytics, ext.8568) |
| 要旨： | Cancer cachexia is a life-threatening syndrome marked by progressive weight loss, adipose tissue browning, and metabolic dysfunction, particularly prevalent in pancreatic ductal adenocarcinoma (PDA). In this talk, I will present our recent work uncovering an iron-regulated signaling axis that drives adipose remodeling in the context of cancer. We identify methionine sulfoxide reductase A (MSRA) as a critical mediator of β 3-adrenergic-induced adipose browning, whose enzymatic activity is modulated through iron-induced multimerization. Genetic deletion of MsrA disrupts adipose thermogenesis, mitigates weight loss, and improves survival in mouse models of PDA. These findings define a novel methionine-based redox switch linking iron metabolism to systemic energy balance and reveal new avenues for therapeutic intervention in cancer cachexia. |