Collaborative Applied Statistics

协作应用统计

• 批准号: 10260281
• 负责人: Alison Motsinger-Reif
• 金额: $ 70.34万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10260281
• 关键词: Adult; Aging; Alzheimer' s Disease; Asthma; Bile Acids; Biological Markers; Blood; Cancer Etiology; Canis familiaris; Cardiovascular Diseases; Chemicals; Child; Chronic Disease; Collaborations; Comet Assay; DNA Damage; DNA Methylation; DNA copy number; Data; Dementia; Development; Diagnostic; Disease; Disease Progression; Disease susceptibility; Environmental Exposure; Environmental Risk Factor; Enzymes; Etiology; Evaluation; Exhibits; Exposure to; Extrinsic asthma; FarGo; Food Hypersensitivity; GSTM1 gene; GSTP1 gene; GSTT1 gene; Gene Expression Profiling; Genes; Genetic; Genetic Enhancement; Genetic Polymorphism; Glutathione S-Transferase; Health; Human; Immune; Leukocytes; London; Lymphoma; Malignant Neoplasms; Mediating; Metabolic; Methods; Modeling; National Institute of Environmental Health Sciences; Non-Hodgkin' s Lymphoma; Nuclear Power Plants; Participant; Pathogenicity; Patients; Peripheral; Pilot Projects; Population; Postdoctoral Fellow; Questionnaires; Registries; Risk; Risk Factors; Sampling; Science; Scientist; Severities; Silicones; Specimen; Universities; Variant; Veterinary Medicine; Wisconsin; Work; asthmatic patient; atopy; base; digital; environmental chemical exposure; epigenome-wide association studies; genetic variant; genome sequencing; genome-wide; improved; metabolomics; method development; neoplastic cell; neuroimaging; novel; novel therapeutics; organic contaminant; recruit; statistics; whole genome

As an interdisciplinary scientist, I work with a number of collaborators both within and outside the NIEHS and applied studies. Such collaborations provide the opportunity to be involved in high impact science, and to realize important gaps in current methods that inspire methods development work. In a continuing collaboration with Dr. Matthew Breen at NCSU, we have completed several studies in this last year related to understanding the genetic and environmental factors that underlie the etiology of cancer in canines as a model for better understanding cancer in humans. A lack of understanding regarding the mechanisms of disease development and progression hinders development of novel therapeutics. Our study aimed to improve the understanding of underlying disease mechanisms using genome-wide DNA copy number and gene expression analysis of spontaneous HM across several dog breeds. Copy Droplet digital PCR evaluation of the regions in numerous cancer specimens effectively discriminated HM from other common round cell tumors resulting in a novel, rapid diagnostic aid for veterinary medicine. Silicone wristbands are promising passive samplers in characterizing exposure to organic contaminants; however, investigating associated health risks remains challenging because of the latency period for many chronic diseases that take years to manifest. In another collaboration with Dr. Breen, we evaluated exposures among pet dogs and their owners using silicone dog tags and wristbands to demonstrate that contaminant levels were correlated with validated exposure biomarkers and demonstrated strong correlations. This supports the value of using silicone bands with dogs to investigate health impacts on humans from shared exposures. I also worked with another collaborator using the canine model - Dr. Lauren Trepanier at the University of Wisconsin. Non-Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S-transferases enzymes. We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and nonboxers using the comet assay. We also compared GST variants and questionnaire-based environmental exposures in boxers with and without lymphoma. Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. Additionally, I collaborated with Dr. Stephanie London here at NIEHS. We conducted the largest epigenome-wide association study of blood DNA methylation in adults in relation to non-atopic and atopic asthma. Participants were categorized as atopy without asthma , non-atopic asthma , atopic asthma , or a reference group of neither atopy nor asthma. Numerous CpGs were differentially methylated in non-atopic asthma and implicated 382 novel genes. More CpGs were identified in atopic asthma and implicated 569 novel genes. I have also continued collaborative work in metabolomics, with Dr. Rima Kaddurah-Daouk. Alzheimer's disease is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related factors. To interrogate the relationship between metabolites and disease susceptibility and progression, we worked with the AD Metabolomics Consortium and AD Neuroimaging Initiative. We used the Biocrates Bile Acids platform to evaluate the association of metabolic levels with disease. A second study with her in metabolomics evaluated metabolomics with food allergy. We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA. In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. We demonstrated that children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. I also have been collaborating with Drs. Janet Hall, David Fargo, Charles Schmitt, Miller and Akhtari on statistical genetics in the Environmental Polymorphisms Registry. We are working on several projects including exposome-wide association studies of both immune mediated disease and cardiovascular disease. I have recently recruited a new post doc fellow, Dr. Eunice Lee to work on these projects. We are currently processing and cleaning the whole genome sequencing data.

作为一名跨学科科学家，我与NIEHS内外的许多合作者和应用研究合作。 这种合作提供了参与高影响力科学的机会，并认识到当前方法中的重要差距，从而激发方法开发工作。 在与NCSU的Matthew Breen博士的持续合作中，我们在过去的一年中完成了几项研究，这些研究涉及了解犬癌症病因的遗传和环境因素，作为更好地了解人类癌症的模型。缺乏对疾病发展和进展机制的理解阻碍了新疗法的开发。我们的研究旨在通过对几个犬种自发性HM的全基因组DNA拷贝数和基因表达分析，提高对潜在疾病机制的理解。对许多癌症标本中的区域进行的拷贝液滴数字PCR评价有效地将HM与其他常见的圆细胞肿瘤区分开来，从而为兽医学提供了一种新型的快速诊断辅助手段。 硅胶腕带是表征有机污染物暴露的有前途的被动采样器;然而，由于许多慢性疾病的潜伏期需要数年才能显现，因此调查相关的健康风险仍然具有挑战性。在与Breen博士的另一项合作中，我们使用硅胶狗牌和腕带评估了宠物狗及其主人的暴露情况，以证明污染物水平与经验证的暴露生物标志物相关，并表现出强烈的相关性。这支持了对狗使用硅胶带来调查共同暴露对人类健康影响的价值。 我还与另一位合作者一起使用犬模型--威斯康星州大学的劳伦·特雷帕尼尔博士。人类非霍奇金淋巴瘤与环境化学品暴露有关，谷胱甘肽S-转移酶的遗传变异增加了风险。我们在犬GSTT 1，GSTT 5，GSTM 1，和GSTP 1的变异位点重新测序，并比较内源性DNA损伤的拳击手和nonboxers使用彗星试验外周血白细胞。我们还比较了GST变体和基于汞的环境暴露在拳击手和没有淋巴瘤。接近核电站，化学品供应商和火葬场是该人群中淋巴瘤的重要危险因素。 此外，我与斯蒂芬妮伦敦博士在NIEHS这里合作。 我们进行了成人血液DNA甲基化与非特应性和特应性哮喘相关的最大的表观基因组关联研究。参与者被分为无哮喘的特应性、非特应性哮喘、特应性哮喘或既无特应性也无哮喘的对照组。在非特应性哮喘中发现了大量CpG的甲基化差异，涉及382个新基因。在特应性哮喘中发现了更多的CpG，涉及569个新基因。 我还继续与Rima Kaddurah-Daouk博士在代谢组学方面进行合作。阿尔茨海默病是痴呆症最常见的原因。疾病发展和进展的机制尚不清楚，但越来越多的证据表明多因素病因学，具有许多遗传，环境和衰老相关因素。为了探究代谢物与疾病易感性和进展之间的关系，我们与AD代谢组学联盟和AD神经影像学倡议合作。我们使用Biocrates胆汁酸平台来评估代谢水平与疾病的相关性。 她在代谢组学方面的第二项研究评估了食物过敏的代谢组学。 我们试图应用非靶向代谢组学分析来确定FA患者的致病机制和候选疾病生物标志物。在这项初步研究中，与对照组和哮喘患者相比，FA患者表现出疾病特异性代谢组学特征。我们证明FA患儿具有疾病特异性代谢组学特征，可提供疾病机制和严重程度的信息，并在哮喘患者中占主导地位。 我还与珍妮特·霍尔、大卫·法戈、查尔斯施密特、米勒和阿赫塔里博士合作，研究环境多态性登记处的统计遗传学。 我们正在开展多个项目，包括免疫介导疾病和心血管疾病的全暴露组关联研究。 我最近招募了一位新的博士后研究员，Eunice Lee博士来从事这些项目。 我们目前正在处理和清理全基因组测序数据。