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 受艾滋病毒感染的人增加了癌症的风险。特别是对于由人类致癌病毒引起的 例如EBV，HPV和KSHV。艾滋病恶性肿瘤是拉丁美洲国家的卫生问题 阿根廷，即使在后哈特时代也是如此。艾滋病毒感染的有关癌症的信息很少 阿根廷的个人。此外，艾滋病的翻译研究是传统上被忽略的领域 大多数阿根廷临床医生和肿瘤学家很少合作的地方。博士的最新努力融合 迈阿密米勒大学医学院西尔维斯特综合癌症中心的梅斯里实验室 （UMMSM/SCCC），Ifibyne - UBA - Conicet的Omar Coso博士和FundroCiónHuésped的Pedro Cahn博士 专门用于艾滋病研究，诊断和预防的最负盛名的ONG已在该财团中融合 U54格式的提案，包括其他每个高级著名的研究人员和初级科学家 财团组成部分。项目1旨在“定义与艾滋病相关病毒中的致癌信号网络 癌症是化学预防和治疗的目标。”该提案将利用各种策略 分子，细胞水平，甚至通过动物模型，以鉴定分子（主要是蛋白质和miRNA） 在病毒癌的发作中实施，并使用不同的 接近和靶向不同的分子。推定的分子被确定为负责 实验室方法的癌症将在项目2的帮助下研究人类样本。 OGB核心将通过使用无偏见的研究能力进一步增强研究能力 基因组分析以及IHC技术，以获取高吞吐量数据，这些数据将验证获得的数据 实验室和促使新问题纳入板凳，使得解决研究问题 仅几年前就无法想象。指导对该项目至关重要。 Coso博士威尔 领导与KS相关的分子信号传导的研究，作为PI项目1。另一方面 凭借在CE核心中的角色，他将监督Ana Raimondi博士，探索针对MTORC1的可能性 在HPV模型中。 Coso博士还将与他的前学员Julian Naipauer博士合作，后者开发了一个新的 KSHV肿瘤发生的细胞和动物模型，在实验室中进行实验以及为 返回阿根廷后，他作为病毒肿瘤学家的科学生涯的未来发展。