The 10th International MDM2 Workshop

第十届国际MDM2研讨会

基本信息

批准号：
10814471
负责人：
Tomoo Iwakuma
金额：
$ 1.5万
依托单位：
CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10814471
关键词：
Acetylation African American Antineoplastic Agents Apoptosis Area Award Basic Science Binding Biology COVID-19 Cancer Biology Cancer Center Career Mobility Cell Cycle Progression Child Cities Clinical Research Clinical Trials Collaborations Communities Complex DNA Repair Doctor of Philosophy Drug Industry Drug Targeting Educational workshop Ensure Europe Event Florida Funding Gene Deletion Gene Mutation Genes Genetic Transcription Goals Grant Hispanic Homologous Gene Human Immunity In Vitro Individual International Japan Location MDM2 Gene Amplification MDM2 gene Malignant Neoplasms Mediating Medicine Mentors Minority Mutate NCI Center for Cancer Research New York Oncogenic Participant Pathway interactions Pharmaceutical Preparations Phosphorylation Play Postdoctoral Fellow Proteins Public Health Reagent Regulation Research Research Institute Research Personnel Role Scientist Senior Scientist Signal Transduction Singapore Students TP53 gene Tokyo Translational Research Travel Tumor Suppressor Proteins Ubiquitination Underrepresented Minority Underrepresented Populations United Kingdom United States Universities Up-Regulation Woman Writing anti-PD-L1 anticancer research cancer immunotherapy career clinically relevant college design drug discovery graduate student in vivo inhibitor interdisciplinary approach man medical schools meetings mouse model overexpression patient subsets public health relevance response social tumor ubiquitin-protein ligase

项目摘要

Project Summary/Abstract The p53 protein is the most frequently mutated gene in human cancers and functions as a tumor suppressor by transcriptionally regulating numerous downstream target genes involved in cell cycle progression and apoptosis. MDM2 and its homolog MDM4 (also known as MDMX) are two of the most important negative regulators of p53 by acting as an E3 ubiquitin ligase complex to promote p53 degradation and by physical binding to inhibit the p53’s transcriptional function. These proteins are also overexpressed in approximately 30% of human cancers. Overexpression of MDM2/MDM4 not only inhibits p53 function, but also shows p53-independent oncogenic activities. Intriguingly, gene amplification of MDM2 and MDM4 is associated with adverse hyperprogressive response to anti-PDL1 cancer immunotherapy in a subset of patients. Thus, inhibitors for MDM2 and MDM4 have been developed to inhibit their oncogenic activities and to reactivate wild-type p53 in tumors. Importantly, some MDM2/MDM4 inhibitors are in clinical trials. The first International MDM2 Workshop, held in 2001 in the United Kingdom, was primarily in response to a significant increase in the research related to p53 and its negative regulators MDM2/MDM4, as well as strong demand for drug discovery targeting MDM2/MDM4/p53. The expansion of the scientific community studying MDM2/MDM4 and the need to pursue this area of research with a collaborative multidisciplinary approach have further made the MDM2 Workshop necessary. The MDM2 Workshop is held every two or three years, at locations alternating between the United States and Europe, to bring together the p53/MDM2 field, present the latest research, and facilitate collaboration and exchange of reagents. Indeed, both the p53 and MDM2 Workshops have become important platforms for long-term scientific exchange and new investigators of the MDM2-p53 pathway. The 10th International MDM2 Workshop will be held at an auditorium of the newly built National Cancer Center Research Institute (NCCRI) in Tokyo, Japan, on October 15-18, 2023. This will be the first International p53/MDM2 Workshop organized and held in Japan. The meeting will be co-organized by Dr. Rieko Ohki (NCCRI, Tokyo, Japan), Dr. Koji Itahana (Duke-NUS Medical School, Singapore), and Dr. Tomoo Iwakuma (Children’s Mercy Research Institute, MO, USA). Notably, due to COVID-19, we have not had the MDM2 Workshop for over 4 years, since the 9th MDM2 Workshop on November 4-7, 2018 in Florida. We expect more participants with higher enthusiasm for this 10th MDM2 Workshop, as compared with the previous MDM2 Workshops. Significant numbers of US researchers, including the international organizing committee (11 out of 16, 38% women), are expected to participate in and benefit from the meeting. Hence, we are applying for R13 funding to support this important and exciting international meeting that will energize research in US and promote scientific progress and interactions in the p53/MDM2 field. Funds are requested to support three important specific aims designed to promote participation of the US investigators and trainees.

项目摘要/摘要 p53蛋白是人类癌症中最常见的突变基因，并用作抑制肿瘤的基因转录控制了涉及细胞周期进程和凋亡的许多下游靶基因。 MDM2及其同源MDM4（也称为MDMX）是p53的两个最重要的负调节剂通过充当E3泛素连接酶复合物来促进p53降解并通过物理结合以抑制 p53的转录功能。这些蛋白质在大约30％的人类癌症中也过表达。 MDM2/MDM4的过表达不仅抑制了p53功能，而且还显示了p53独立的致癌性活动。有趣的是，MDM2和MDM4的基因扩增与不良超前有关一部分患者对抗PDL1癌症免疫疗法的反应。那是MDM2和MDM4的抑制剂已经开发出来抑制其致癌活性并重新激活肿瘤中的野生型p53。重要的是，一些MDM2/MDM4抑制剂正在临床试验中。 2001年在2001年举行的第一个国际MDM2研讨会英国主要是为了回应与p53及其负面的研究大幅增加调节剂MDM2/MDM4，以及针对MDM2/MDM4/p53的药物发现的强烈需求。这扩展研究MDM2/MDM4的科学界以及与此研究领域的需求一种协作的多学科方法进一步使MDM2研讨会需要。 MDM2 研讨会每两三年举行一次，在美国和欧洲之间的替代地点将p53/MDM2领域汇总在一起，介绍最新的研究，并促进合作和交流试剂。实际上，p53和MDM2研讨会已成为长期科学的重要平台 MDM2-P53途径的交换和新研究人员。第十次国际MDM2研讨会将举行在日本东京的新建国家癌症中心研究所（NCCRI）的礼堂上 2023年10月15日至18日。这将是在日本组织和举行的第一个国际P53/MDM2研讨会。这会议将由Rieko Ohki博士（NCCRI，东京，日本），Koji Itahana博士（Duke-Nus Medical）共同组织新加坡学校）和Tomoo Iwakuma博士（美国密苏里州儿童慈悲研究所）。值得注意的是，由于 Covid-19，自11月9日的MDM2研讨会以来，我们已经有4年以上的MDM2研讨会了 4-7，2018在佛罗里达州。我们希望对这个第10个MDM2研讨会的热情更加热情，因为与以前的MDM2研讨会相比。美国大量研究人员，包括国际组织委员会（16名中有11名妇女）有望参加并从中受益会议。因此，我们正在申请R13资金来支持这次重要而激动人心的国际会议这将激发美国的研究，并促进p53/MDM2领域的科学进步和相互作用。资金要求支持三个旨在促进美国调查人员参与的重要特定目标和受训者。