Molecular Epidemiology of B cell Activation, DNA Repair & HIV-Associated Lymphoma

B 细胞激活、DNA 修复的分子流行病学

• 批准号: 8721346
• 负责人: Shehnaz Khursheed Hussain
• 金额: $ 12.52万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721346
• 关键词: AIDS-Related Lymphoma; AIDS-Related Non-Hodgkin' s Lymphoma; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Age; American; Amino Acid Substitution; Anti-Retroviral Agents; B-Cell Activation; B-Lymphocytes; Binding Sites; Bioinformatics; Biological; Biological Markers; CD8B1 gene; CXCL13 gene; Cancer Immunology Science; Candidate Disease Gene; Cell Count; Cessation of life; Chronic; Clinical; Cohort Studies; Collaborations; Complex; Computational Biology; Computer Simulation; DNA Repair; Data; Data Analyses; Databases; Detection; Development; Development Plans; Doctor of Philosophy; Early Diagnosis; Environment; Epidemiological Factors; Epidemiology; Etiology; Factor Analysis; Family history of; Future; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Grant; HIV; HIV Seropositivity; HIV therapy; Habits; Haplotypes; Human Herpesvirus 4; Immune System Diseases; Immunoglobulin Class Switching; Immunoglobulin Genes; Immunoglobulin Somatic Hypermutation; Immunoglobulin Switch Recombination; Immunologic Deficiency Syndromes; Incidence; Individual; Infectious Agent; Institutes; Linkage Disequilibrium; Logistic Regressions; Lymphomagenesis; Manuscripts; Mentors; Modeling; Molecular; Molecular Epidemiology; Molecular Epidemiology of Cancer; Molecular Genetics; Natural History; Nested Case-Control Study; Non-Hodgkin' s Lymphoma; Other Genetics; Pathogenesis; Pathway interactions; Pattern; Peripheral Blood Mononuclear Cell; Population; Postdoctoral Fellow; Predisposition; Prevention; Probability; Public Health; Research; Research Design; Research Personnel; Research Project Grants; Resources; Risk; Risk Assessment; Role; Schools; Scientist; Serum; Somatic Mutation; Statistical Methods; T-Lymphocyte; Techniques; Testing; Training; Tumor Subtype; Tumor Suppressor Genes; Woman; Writing; activation-induced cytidine deaminase; base; career; career development; chemokine; cigarette smoking; cohort; comparative genomics; cytokine; data reduction; design; experience; genetic risk factor; genome wide association study; high risk; high throughput technology; immunoregulation; infected B cell; infection related cancer; inflammatory marker; innovation; meetings; member; molecular marker; mortality; professor; programs; prospective; public health relevance; repaired; therapeutic development; transcription factor; tumor; years of life lost

DESCRIPTION (provided by applicant): This proposal describes a five-year program designed in the short-term to provide additional specific training and mentored research experience to Dr. Shehnaz K. Hussain to enable her to achieve her long-term goal of successfully launching a career as an independent academic researcher and scientist in cancer molecular epidemiology with a focus on infection-related cancers. Dr. Hussain received a Sc.M. in epidemiology from Johns Hopkins, a Ph.D. in epidemiology from U. W. Seattle, was a postdoc at the Karolinska Institute, and is currently a newly appointed Assistant Professor in the UCLA Department of Epidemiology. Dr. Hussain will meet her academic career goals with the help of a highly experienced and supportive interdisciplinary team of mentors including Drs. Zhang (cancer molecular epidemiology), Martinez-Maza (cancer immunology), Detels (HIV/AIDS epidemiology), and Sinsheimer (statistical genetics); a clear and directed career development plan including grant and manuscript writing, didactic training in computational biology, bioinformatics, complex data analysis, and issues in the design/conduct of genome wide association studies, and wet-lab training; a strong and collaborative institutional environment consisting of multiple centers, departments, and schools of UCLA; and a well-defined research project with a high possibility of being developed into an independent research program. The main hypothesis of Dr. Hussain's research project is that adverse genotypes of B cell activation-related genes will be associated with increased risk of HIV-associated non-Hodgkin's lymphoma (AIDS-NHL). Dr. Hussain will conduct a nested case-control study in two well-described HIV cohorts, the MACS and WIHS. TagSNPs in candidate genes, prioritized by putative functionality, will be genotyped in AIDS-NHL cases and matched controls. Multivariate logistic regression models and pathway-based statistical methods will be utilized to determine the association between tagSNPs and haplotypes and AIDS-NHL risk, and to examine whether these associations are modified by other genetic, molecular, or epidemiological factors. This project will integrate high-throughput technologies, innovative statistical methods, and a wealth of previously collected data to extend our understanding of NHL etiology.

描述(由申请人提供)：这份建议书描述了一个短期内设计的五年计划，旨在为Shehnaz K.Hussain博士提供额外的具体培训和有指导的研究经验，使她能够实现她的长期目标，即成功地开始她的职业生涯，成为癌症分子流行病学的独立学术研究员和科学家，专注于与感染相关的癌症。侯赛因博士在约翰·霍普金斯大学获得流行病学理学硕士学位，在西雅图大学获得流行病学博士学位，是卡罗林斯卡研究所的博士后，目前是加州大学洛杉矶分校流行病学系新任命的助理教授。Hussain博士将在以下导师的帮助下实现她的学术职业目标：由张博士(癌症分子流行病学)、Martinez-Maza博士(癌症免疫学)、Detels博士(艾滋病毒/艾滋病流行病学)和Sinshemer博士(统计遗传学)组成的经验丰富和支持的跨学科导师团队；明确和定向的职业发展计划，包括拨款和手稿写作、计算生物学、生物信息学、复杂数据分析和全基因组关联研究设计/实施中的问题，以及湿实验室培训；由加州大学洛杉矶分校的多个中心、系和学校组成的强大和协作的机构环境；以及明确的研究项目，很有可能发展为独立的研究项目。侯赛因博士研究项目的主要假设是，B细胞激活相关基因的不利基因型将与艾滋病毒相关性非霍奇金淋巴瘤(AIDS-NHL)风险增加相关。侯赛因博士将在两个描述良好的HIV队列中进行嵌套病例对照研究，这两个队列分别是MACS和WIHS。候选基因中的TagSNP按推测的功能优先，将在AIDS-NHL病例和匹配的对照组中进行基因分型。多变量Logistic回归模型和基于路径的统计方法将被用来确定标签SNPs和单倍型与AIDS-NHL风险之间的关联，并检查这些关联是否被其他遗传、分子或流行病学因素改变。这个项目将结合高通量技术、创新的统计方法和之前收集的大量数据来扩大我们对NHL病因学的理解。