Association of Phenotypes and Genotype with Treatment Response in Psoriatic Arthritis

表型和基因型与银屑病关节炎治疗反应的关联

• 批准号: 10723557
• 负责人: Paras Karmacharya
• 金额: $ 16.34万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-14 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723557
• 关键词: Academic Medical Centers; Active Learning; Address; Affect; Algorithms; American; Anxiety; Artificial Intelligence; Bioinformatics; CCL18 gene; Characteristics; Chronic; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials Design; Cluster Analysis; Complement; Computational Science; Data; Databases; Development; Development Plans; Disease; Disease Progression; Disease remission; Electronic Health Record; Electronics; Environment; Fostering; Foundations; Funding; Future; Genetic; Genetic Heterogeneity; Genetic Risk; Genetic Variation; Genetic study; Genotype; Goals; Immunology; Individual; Inflammatory; Institution; International; International Classification of Disease Codes; Knowledge; Link; Longitudinal cohort; Measures; Mental Depression; Mentors; Methods; Mission; Musculoskeletal; Musculoskeletal Diseases; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Obesity; Outcome; Patients; Phenotype; Positioning Attribute; Postdoctoral Fellow; Prediction of Response to Therapy; Probability; Prognosis; Psoriatic Arthritis; Publishing; Recommendation; Records; Research; Research Personnel; Research Project Grants; Resources; Rheumatology; Sample Size; Sampling; Severities; Skin; Statistical Methods; Stratification Factors; Subgroup; System; Techniques; Therapeutic; Training; Translational Research; Work; arthritis therapy; biobank; biomedical informatics; career; career development; clinical data warehouse; clinical heterogeneity; clinical training; cohort; comorbidity; design; effective therapy; epidemiology study; experience; follow-up; improved; innovation; instructor; novel; patient oriented; patient population; patient subsets; personalized approach; personalized medicine; phenome; polygenic risk score; pragmatic trial; precision medicine; predictive marker; predictive modeling; prospective; research study; response; side effect; skills; skin disorder; treatment responders; treatment response; treatment strategy

PROJECT SUMMARY Candidate: Paras Karmacharya, MD MS is a Clinical Instructor at Vanderbilt in the Divisions of Rheumatology & Immunology. He has a strong clinical background in rheumatology and an excellent scientific foundation in epidemiological studies from his Master’s in Clinical and Translational Science and post-doctoral research studies following clinical training. His long-term career plan is to become an independent clinical investigator and a leader in pursuing patient-centered, pragmatic research in real-world psoriatic arthritis (PsA) patients and advancing personalized medicine in PsA. To achieve this goal, he will utilize his proposed research project for hands-on training in advanced statistical methods, bioinformatics, and genetics. Research Project: This proposal will study the association of clinical and genetic heterogeneity in PsA with treatment response. Using two unique real-world PsA cohorts, Dr. Karmacharya will (1) Identify PsA phenotypes and their association with treatment response in PsA, and (2) Identify PsA patients with a high probability of responding to therapy and those with a low probability of responding to therapy in the EHR. These aims are foundational to designing future pragmatic trials leveraging the EHR to more efficiently and robustly develop personalized approaches to treatment. Career Development: Dr. Karmacharya’s career development plan integrates formal coursework with individual training from his mentors to (1) Enhance skills in advanced statistical methods, (2) Expand proficiency in applying biomedical informatics techniques to large databases through mentored hands-on training in Vanderbilt’s EHR, (3) Build foundational knowledge in genetics and through experiential learning to apply analytic techniques to a genetic biobank, and (4) Develop expertise in building and managing a prospective PsA cohort. Environment: VUMC is the ideal environment to foster Dr. Karmacharya’s development as a leader in clinical and translational research in PsA. His mentoring team includes experts in PsA (Ogdie/Ritchlin), advanced statistical methods (Byrne/Chen/Ogdie), biomedical informatics (Byrne/Barnado), and genetics (Cox). Additional institutional resources include the Synthetic Derivative (SD), a de-identified EHR with over 3.5 million subjects, and BioVU, a genetic biobank linked to the SD, and departmental support for his multicenter PsA cohort. His mentors, Drs. Crofford and Ogdie, are internationally recognized in rheumatology and PsA with successful track records of mentoring. With Vanderbilt’s institutional commitment to young investigators and expertise in biomedical informatics and genetics, Dr. Karmacharya will successfully leverage his innovative proposal for independent R01 funding.

项目概要 候选人：Paras Karmacharya，医学博士 MS 是范德比尔特大学风湿病科的临床讲师 他在风湿病学和免疫学方面拥有深厚的临床背景和良好的科学基础。 他在临床和转化科学硕士学位以及博士后研究中进行了流行病学研究 他的长期职业计划是成为一名独立的临床研究者。 以及对现实世界的银屑病关节炎 (PsA) 患者进行以患者为中心的务实研究的领导者 为了实现这一目标，他将利用他提出的研究项目。 进行高级统计方法、生物信息学和遗传学的实践培训。 研究项目：本提案将研究 PsA 的临床和遗传异质性与 Karmacharya 博士使用两个独特的现实世界银屑病关节炎队列 (1) 识别银屑病关节炎。 表型及其与 PsA 治疗反应的关联，以及 (2) 识别具有高 EHR 中对治疗有反应的概率以及对治疗有低概率反应的人。 这些目标是设计未来实用试验的基础，利用 EHR 更高效、更高效地进行临床试验。 大力发展个性化治疗方法。 职业发展：Karmacharya 博士的职业发展计划将正式课程与 导师的个人培训旨在 (1) 增强高级统计方法的技能，(2) 扩展 通过指导实践，熟练地将生物医学信息学技术应用于大型数据库 范德比尔特电子病历培训，(3) 建立遗传学基础知识，并通过体验式学习 将分析技术应用于遗传生物库，以及 (4) 发展建立和管理基因生物库的专业知识 前瞻性 PsA 队列。 环境：VUMC 是促进 Karmacharya 博士发展成为临床领导者的理想环境 他的指导团队包括 PsA 专家（Ogdie/Ritchlin）、高级专家。 统计方法（Byrne/Chen/Ogdie）、生物医学信息学（Byrne/Barnado）和遗传学（Cox）。 其他机构资源包括合成衍生物 (SD)，这是一种去识别化的 EHR，具有超过 3.5 百万受试者，BioVU，一个与 SD 相关的基因生物库，以及对其多中心的部门支持 他的导师 Crofford 和 Ogdie 博士在风湿病学和 PsA 领域享有国际认可。 凭借范德比尔特对年轻研究人员的机构承诺和成功的指导记录。 Karmacharya 博士凭借生物医学信息学和遗传学方面的专业知识，将成功利用他的创新 独立 R01 资助的提案。

项目成果

Effect of Biologics in Subgroups of Axial Spondyloarthritis Based on Magnetic Resonance Imaging and C-Reactive Protein: A Systematic Review and Meta-Analysis.

基于磁共振成像和 C 反应蛋白的生物制剂对中轴型脊柱关节炎亚组的影响：系统评价和荟萃分析。

• 发表时间: 2023-09
• 影响因子: 3.4
• 作者: Karmacharya, Paras;Gupta, Sonia;Shahukhal, Ravi;Khanal, Raju;Murad, M Hassan;Gensler, Lianne S
• 通讯作者: Gensler, Lianne S