Identifying the vulnerabilities in Mdm2 overexpressing cancer cells

摘要 P53途径的紊乱是大多数(如果不是全部)人类癌症的共同主题。在衰减的同时 通路最常通过p53基因本身的突变或缺失、扩增或过度生产而发生 在两种重要的p53抑制物中，MDM2和MDM4也出现在许多癌症中。研究计划 由R01资助的CA47296研究肿瘤抑制的途径，重点是MDM2的作用 和MDM4在P53调控中，目前处于其供资的第31个年头。这个R50应用程序请求工资 支持Vinod Pant博士继续为该项目提供研究支持。潘特博士是一名非 Guillermina Lozano博士的实验室终身助理教授，单位主任关于这一申请。潘特博士 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。潘特博士对 项目，并在知名期刊上发表了多篇研究文章。与此应用程序相关，Dr。 PANT精通小鼠研究和CRISPR/Cas9功能筛查。潘特博士已经进行了 初步筛选，以确定允许细胞耐受高水平MDM2的因素 对正常细胞生长有毒性。潘特博士正在进行二次筛查，以进一步完善结果。在……里面 此外，潘特博士将对MDM2过表达的脂肪肉瘤细胞进行基因筛查，以确定 这些癌细胞的脆弱性。已确定的因素将通过体外和体内研究和 随后作为潜在治疗策略的治疗靶点进行了测试。潘特博士的贡献是至关重要的 为顺利完成R01 CA47296研究计划的目标。

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.