Identifying the vulnerabilities in Mdm2 overexpressing cancer cells

识别 Mdm2 过度表达癌细胞的脆弱性

• 批准号: 10040521
• 负责人: Vinod Pant
• 金额: $ 8.37万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-11 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10040521
• 关键词: Biochemistry; CRISPR/Cas technology; Cells; Developmental Biology; Doctor of Philosophy; Funding; Genetic Screening; Human; In Vitro; Journals; Laboratories; MDM2 gene; Malignant Neoplasms; Molecular Biology; Mus; Mutation; Normal Cell; Pathway interactions; Production; Protein p53; Publishing; Regulation; Request for Applications; Research; Research Support; Role; TP53 gene; Testing; Tumor Suppression; Wages; Work; anticancer research; attenuation; cancer cell; cell growth; experience; experimental study; genome-wide; in vivo; inhibitor/antagonist; liposarcoma; mouse genetics; overexpression; professor; programs; therapeutic target; treatment strategy; tumor

Abstract Perturbation of the p53 pathway is a common theme in most if not all human cancers. While attenuation of the pathway occurs most often through mutation or deletion of the p53 gene itself, amplification or over production of two important p53 inhibitors, MDM2 and MDM4 also occurs in a number of cancers. The research program funded by R01 CA47296 investigates the pathways of tumor suppression with emphasis on the role of Mdm2 and Mdm4 in p53 regulation and is currently in its 31st year of funding. This R50 application requests salary support for Vinod Pant, Ph.D. to continue providing research support to the program. Dr. Pant works as a non- tenure Assistant Professor in the laboratory of Dr. Guillermina Lozano, Unit Director on this application. Dr. Pant has more than 15 years of experience in cancer research and has a broad background in molecular biology, developmental biology, bio-chemistry and mouse genetics. Dr. Pant has made significant contributions to the program and has published multiple research articles in well-regarded journals. Relevant to this application, Dr. Pant is proficient in murine studies and in conducting CRISPR/Cas9 functional screens. Dr. Pant has carried out preliminary screens to identify the factors that allow cells to tolerate high levels of MDM2 which are otherwise toxic for normal cell growth. Dr. Pant is proceeding with secondary screens to further refine the results. In addition, Dr. Pant will perform genetic screens in MDM2 overexpressing liposarcoma cells to identify the vulnerabilities in these cancer cells. Identified factors will be validated by in vitro and in vivo studies and subsequently tested as therapeutic targets for potential treatment strategy. Dr. Pant's contribution is essential for successful completion of the aims of R01 CA47296 research program.

摘要 p53通路的扰动是大多数（如果不是所有）人类癌症的共同主题。而衰减的 p53基因自身的突变或缺失、扩增或过度表达是p53基因表达途径中最常见的途径 在两种重要的p53抑制剂中，MDM 2和MDM 4也出现在许多癌症中。研究计划 由R 01资助的CA 47296研究了肿瘤抑制的途径，重点是Mdm 2的作用 和MDM 4在p53监管，目前在其第31年的资金。此R50申请要求工资 支持Vinod Pant博士继续为该项目提供研究支持。潘特医生是一名非- 在Guillermina Lozano博士实验室的终身助理教授，该申请的单位主任。潘特医生 拥有超过15年的癌症研究经验，并具有广泛的分子生物学背景， 发育生物学、生物化学和小鼠遗传学。Pant博士为该领域做出了重大贡献。 计划，并已发表多篇研究文章在备受推崇的期刊。关于这个应用程序，博士。 Pant精通小鼠研究和进行CRISPR/Cas9功能筛选。潘特医生已经进行了 初步筛选以确定允许细胞耐受高水平MDM 2的因素，而这些因素在其他情况下是不允许的 对正常细胞生长有害潘特博士正在进行二次筛选，以进一步完善结果。在 此外，Pant博士将在MDM 2过表达脂肪肉瘤细胞中进行基因筛查，以识别 这些癌细胞的弱点。将通过体外和体内研究验证已确定的因素， 随后作为潜在治疗策略的治疗靶点进行测试。潘特博士的贡献至关重要 成功完成R 01 CA 47296研究计划的目标。