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概要 艾滋病毒感染者有患呼吸系统癌症的风险，特别是那些由人类致癌病毒引起的人。 EBV、HPV 和 KSHV 等恶性肿瘤是拉丁美洲国家的一个卫生问题。 阿根廷，即使在后 HAART 时代，关于艾滋病毒感染者癌症的信息也很少。 此外，艾滋病恶性肿瘤的转化研究历来被忽视。 大多数阿根廷超级明星和肿瘤学家很少合作。 迈阿密大学米勒医学院西尔维斯特综合癌症中心 Mesri 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 汇聚在这个联盟中 U54格式下的提案，包括各个领域的其他高级著名研究人员和青年科学家 联盟组成部分项目 1 旨在“定义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。” 分子、细胞水平甚至通过动物模型来识别分子（主要是蛋白质和miRNA） 与病毒性癌症的发生有关，并使用不同的方法研究其与 HIV 感染的关系 方法和针对被确定为负责发病的不同分子。 将在项目 2 的帮助下通过实验室方法对人体样本中的癌症进行研究。 OGB 核心将通过使用公正的方法进一步增强研究能力 基因组分析以及 IHC 技术，以获得高通量数据，以验证在 实验室并提出新的问题，使解决研究问题成为可能 就在几年前，这还是不可想象的。指导对于这个项目至关重要。 作为项目 1 的 PI，领导 KS 相关分子信号传导的研究。另一方面，结合 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 Coso 博士还将与他的前实习生 Julian Naipauer 博士合作，后者开发了一种新的 HPV 模型。 KSHV 肿瘤发生的细胞和动物模型，在实验室进行实验并指导 返回阿根廷后，他作为病毒肿瘤学家的科学事业的未来发展。