Research Project 1 Defining oncogenic signaling networks in AIDS-associated viral cancers as targets of chemoprevention and treatment

研究项目 1 将艾滋病相关病毒癌症中的致癌信号网络定义为化学预防和治疗的目标

• 批准号: 10488067
• 负责人: Omar Adrian Coso
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10488067
• 关键词: Acquired Immunodeficiency Syndrome; Address; Animal Model; Anus; Area; Argentina; Argentine; Back; Cell Cycle; Cell model; Cells; Chemoprevention; Chemopreventive Agent; Clinical; Clinical Data; Comprehensive Cancer Center; Country; Data; Development; Diagnosis; Dissection; Epithelial; FRAP1 gene; Future; Genes; Genetic Transcription; Genomics; HIV; HIV Infections; Head and neck structure; Heightened Cancer Risk; Highly Active Antiretroviral Therapy; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Human papillomavirus 16; Individual; Laboratories; Latin American; Lead; Malignant - descriptor; Malignant Neoplasms; Mediating; Mentors; Mesenchymal Stem Cells; Messenger RNA; Metformin; MicroRNAs; Modeling; Molecular; Mutation; Oncogenes; Oncogenic; Oncogenic Viruses; Oncologist; Outcome; PDGFRA gene; PTGS2 gene; Pathogenesis; Pathway interactions; Phosphotransferases; Platelet-Derived Growth Factor; Postdoctoral Fellow; Prevention; Proteins; Proto-Oncogene Proteins c-akt; Regulation; Research; Research Personnel; Research Project Grants; Research Training; Role; Sampling; Scientist; Signal Pathway; Signal Transduction; Supervision; Techniques; Therapeutic; Time; Translational Research; Universities; Up-Regulation; Vascular Endothelial Growth Factors; Viral; Viral Cancer; Viral Genes; Viral Oncogene; Virus; angiogenesis; cancer cell; career; clinically significant; cyclooxygenase 2; experimental study; medical schools; mutant; neglect; overexpression; tumor; tumorigenesis; virus genetics; virus related cancer

Research Project 1 Summary HIV infected individuals have heightened cancer risk. Particularly for those caused by human oncogenic viruses such as EBV, HPV and KSHV. AIDS Malignancies are a sanitary problem for Latin American Countries as Argentina, even in the post HAART era. There is scant information regarding cancer among HIV-infected individuals in Argentina. Moreover, translational research in AIDS malignancies is an area traditionally neglected where most Argentinean clinicians and oncologists rarely collaborate. The recent convergence of efforts of Dr. Mesri laboratory at University of Miami Miller School of Medicine's Sylvester Comprehensive Cancer Center (UMMSM/SCCC), Dr.Omar Coso at IFIBYNE – UBA – CONICET and Dr. Pedro Cahn from Fundación Huésped the most prestigious ONG devoted to AIDS studies, diagnosis and prevention have converged in this consortium proposal under the U54 format, including other Senior Prestigious Researchers and Junior Scientists in every Consortium Component. Project 1 aims to “Define oncogenic signaling networks in AIDS-associated viral cancers as targets of chemoprevention and treatment.” The proposal will make use a variety of strategies at the molecular, cellular level and even through animal models to identify molecules (mainly proteins and miRNAs) implicated in the onset of viral cancers and investigate its relationship with HIV infection, using different approaches and targeting different molecules. Putative Molecules identified as responsible for the onset of cancer by laboratory approaches will be studied in Human Samples with the aid of Project 2. Relationship with the OGB Core will allow enhancement of the research capabilities a significant step further by using unbiased genomic analysis, as well as IHC techniques, to obtain high throughput data that will validate data obtained in the laboratory and prompt new questions into the bench making possible to address research questions that were unimaginable only a few years back. Mentoring is of paramount importance to this project. Dr Coso will lead the studies in KS related molecular signaling working as a PI to Project 1. On the other hand and combining with his role in the CE Core, he will supervise Dr Ana Raimondi, exploring the possibility of targeting mTORC1 in HPV models. Dr. Coso will also team with his former trainee Dr Julian Naipauer, who has developed a new cell and animal model of KSHV oncogenesis, conducting experiments in the laboratory and mentoring for the future development of his scientific career as a viral oncologist upon return to Argentina.

研究项目1摘要 艾滋病毒感染者增加了患癌症的风险。尤其是由人类致癌病毒引起的 如EBV、HPV和KSHV。艾滋病是拉丁美洲国家的一个卫生问题，因为 阿根廷，即使是在后HAART时代。在艾滋病毒感染者中，关于癌症的信息很少。 阿根廷的个人。此外，艾滋病恶性疾病的翻译研究是一个传统上被忽视的领域 大多数阿根廷临床医生和肿瘤学家很少合作。他最近的努力集中在一起。 迈阿密大学米勒医学院西尔维斯特综合癌症中心梅斯里实验室 (UMMSM/SCCC)，IFIBYNE-UBA-CONICET的Omar Coso博士和Fundación Huésped的Pedro Cahn博士 致力于艾滋病研究、诊断和预防的最负盛名的ONG已经汇聚到这个联盟 U54格式下的提案，包括每个项目中的其他高级著名研究人员和初级科学家 联合体组件。项目1旨在“确定艾滋病相关病毒中的致癌信号网络 癌症作为化学预防和治疗的目标。该提案将在 分子、细胞水平，甚至通过动物模型识别分子(主要是蛋白质和miRNAs) 与病毒性癌症的发病有关，并研究其与艾滋病毒感染的关系，使用不同的方法 方法和目标不同的分子。被确认为导致疾病发生的可能分子 实验室方法的癌症将在项目2的帮助下在人体样本中进行研究。 OGB核心将允许进一步增强研究能力，通过使用无偏见的 基因组分析以及IHC技术，以获得高通量数据，从而验证在 实验室并提示新的问题，使解决研究问题成为可能， 就在几年前是不可想象的。指导对这个项目来说是至关重要的。科索博士将 领导KS相关分子信号转导的研究，作为PI作用于项目1。另一方面，结合 由于他在行政长官核心的角色，他将监督Ana Raimondi博士，探索以mTORC1为目标的可能性 在人乳头瘤病毒模型中。科索博士还将与他以前的实习生朱利安·奈保尔博士合作，后者已经开发出一种新的 KSHV致癌的细胞和动物模型，实验室实验和指导 回到阿根廷后，他作为病毒肿瘤学家的科学生涯的未来发展。