Diversity Supplement: Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury

多样性补充剂：引导色氨酸免疫代谢改善肝脏缺血再灌注损伤

• 批准号: 10632561
• 负责人: Benjamin George Keselowsky
• 金额: $ 3.75万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10632561
• 关键词: Address; Anti-Inflammatory Agents; Biological; Blood Circulation; Blood flow; Catalogs; Cell Death; Cells; Clinical; Data; Disease; Enzymes; Foundations; Future; Immune; Immunocompromised Host; Inflammation; Injectable; Ischemia; Liver; Liver Dysfunction; Liver Failure; Metabolic; Myocardial Infarction; Operative Surgical Procedures; Organ; Organ failure; Pharmaceutical Preparations; Reperfusion Injury; Stroke; Technology; Therapeutic; Tissues; Toxic effect; Transplantation; Trauma; Tryptophan; Tryptophan Metabolism Pathway; Vascular blood supply; base; clinical practice; in vivo; innovation; liver ischemia; novel therapeutics; preconditioning; programs; side effect; success; systemic toxicity

Contact PD/PI: Keselowsky, Benjamin G Project Summary/Abstract Many different disease states and surgical interventions result in a period of inadequate tissue/organ blood supply (i.e., ischemia), that result in reperfusion injury when blood flow is restored, known as ischemia-reperfusion injury (IRI). IRI causes local inflammation, cell death, excessive tissue destruction and possible organ failure. Examples are found in transplantation, trauma, myocardial infarction, stroke, and in particular, IRI is a main cause of liver dysfunction and failure after liver surgery. Unfortunately, there are currently no therapies available in clinical practice addressing IRI, where a major problem is the harmful systemic side effects and toxicities of existing drugs. To address this problem, we are innovating a new therapeutic technology aiming to program immune cells toward a metabolic state blocking excessive inflammation by directing tryptophan metabolism through delivery of an enzyme into circulation. This represents a new class of anti- inflammatory/immunosuppressive biologic drug, with potential to limit systemic toxicities/side effects, and with potential to be significantly less immunocompromising. Lack of treatment options for liver IRI and a catalog of in vivo preliminary data strongly supporting the foundational rationale of IDO as an innovative new anti-inflammatory agent, make this proposal highly significant. Looking to the future, success would open opportunity to expand to other anti-inflammatory applications, for example, pre-conditioning donor grafts for transplantation. Project Summary/Abstract Page 6

联系PD/PI: Keselowsky， Benjamin G