Association of Phenotypes and Genotype with Treatment Response in Psoriatic Arthritis

项目概要 候选人：Paras Karmacharya，医学博士 MS 是范德堡大学风湿病科的临床讲师 & 免疫学。他在风湿病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 临床培训后的研究。他的长期职业规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 并推进银屑病关节炎的个性化医疗。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 治疗反应。 Karmacharya 博士利用两个独特的现实世界 PsA 队列， (1) 识别 PsA 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 更有效、更高效地进行试验。 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 以及 PsA 的转化研究。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 PsA 队列。他的导师，博士。 Crofford 和 Ogdie 在风湿病学和银屑病关节炎领域获得国际认可 指导的成功记录。凭借范德比尔特对年轻研究人员的机构承诺和 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。

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.