Molecular Pharmacology Lab

分子药理学实验室

• 批准号: 10819428
• 负责人: LEONARD FREEDMAN
• 金额: $ 104.39万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-31 至 2023-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10819428
• 关键词: Acute Myelocytic Leukemia; Acute Promyelocytic Leukemia; Agonist; Anaphase; Aneuploidy; Antineoplastic Agents; Biological Assay; Chimeric Proteins; Differentiation Therapy; Etiology; FDA approved; Genetic; Immunotherapy; Laboratories; Malignant Neoplasms; Molecular; Normal Cell; Pathway interactions; Pharmacology; Play; RXR; Retinoic Acid Receptor; Retinoids; Signal Transduction; antagonist; combat; companion diagnostics; retinoic acid receptor alpha; targeted cancer therapy; tool; ubiquitin isopeptidase

This laboratory uses retinoic acid receptor (RAR, retinoid) and retinoid X receptor (RXR, rexinoid) agonists or antagonists and other agents as discovery tools to uncover critical antineoplastic pathways. The laboratory played a key role in identifying retinoid-based differentiation therapy as a successful (and FDA-approved) way to combat acute promyelocytic leukemia (APL), an early example of targeted cancer therapy. This team cloned the etiologic fusion protein, PML/RARα, and developed the companion diagnostic genetic assay for Acute Promyelocytic Leukemia (APL). Currently, they are exploring the retinoid-regulated deubiquitinase USP18 and how retinoids cooperate in immune-based therapy. Recently, they discovered a pathway called anaphase catastrophe that can target aneuploid cancers (a hallmark of cancer) while sparing normal cells. Signals that trigger anaphase catastrophe are now under intensive study.

该实验室使用视黄酸受体（RAR，类视黄醇）和类视黄酸 X 受体（RXR，类视黄醇）激动剂或拮抗剂以及其他药物作为发现工具，以揭示关键的抗肿瘤途径。该实验室在确定基于类视黄醇的分化疗法作为一种治疗方法方面发挥了关键作用。治疗急性早幼粒细胞白血病（APL）的成功（并获得 FDA 批准）的方法，这是靶向癌症治疗的早期例子，该团队克隆了病因融合蛋白， PML/RARα，并开发了急性早幼粒细胞白血病（APL）的伴随诊断基因检测。目前，他们正在探索类维生素A调节的去泛素酶USP18以及类维生素A如何在基于免疫的治疗中发挥作用。最近，他们发现了一种称为后期灾难的途径。可以针对非整倍体癌症（癌症的标志），同时不伤害正常细胞，目前正在深入研究引发后期灾难的信号。