Immunophenotypes in the Idiopathic Inflammatory Myopathies

项目总结 候选人：Erin Wilfong博士，医学博士，博士，范德比尔特大学医学中心临床讲师 过敏、肺部和重症监护内科以及风湿病和免疫科。她有一种强烈的 风湿病和肺病学的临床背景，在化学方面有很好的科学基础 她的博士和博士后研究中的生物学和翻译免疫学 在临床培训之后。她的长期职业计划是成为炎症性疾病领域的顶尖内科科学家 肌炎侧重于利用尖端技术来识别疾病的发病机制和新颖 治疗靶点。为了实现这一目标，她的直接目标是(1)学习必要的生物信息学技术 独立分析高维免疫表型和转录图谱，并将这些 以及(2)应用分子免疫学技术来确定调节失调 IIM特异性细胞群体中的通路。 研究项目：该提案将研究IIM的潜在免疫异质性，并确定 免疫/转录特征与临床特征之间的关系。Wilfong博士将(1)确定 使用横断面IIM队列的IIM患者的免疫特征和转录异常，(2)相关 纵向IIM队列中ILD进展的免疫特征。她还将接受先前的单细胞RNA- SEQ发现和(3)进行机制研究，调查氧化还原传感器TXNIP的上调如何改变 Jo1+抗tRNA合成酶综合征的免疫代谢。 职业发展：Wilfong博士的职业发展计划将正式课程与个性化课程相结合 来自她的导师和合作者的培训：(1)掌握R编程，以便于分析 使用尖端分析工具的免疫表型和转录数据集，(2)学习生物统计学 适当地将免疫学结果与临床表型相关联所需的原则，(3)表征 使用体外测试的细胞功能，以及(4)发展必要的领导力和沟通技能 成为应用本K08奖项的科学发现和方法的首席研究员 走向未来的翻译免疫学R01。 环境：VUmc是培养Wilfong博士成为翻译领先者的理想环境 免疫学和炎症性肌炎。Wilfong博士的指导团队包括炎症方面的专家 肌炎(Crofford/Aggarwal)，免疫代谢(Rathmell)，单细胞RNA序列(Kropski)，以及 计算免疫学(乔治耶夫)。除了拥有必要的导师和设备外，71.3%的 范德比尔特大学医学中心职业发展奖获得者(n=236)已成功获得 自1999年以来的R级供资。克罗福德博士和拉斯梅尔博士成功地培养了许多内科科学家 并将确保Wilfong博士成为一名独立资助的内科科学家。

PROJECT SUMMARY Candidate: Dr. Erin Wilfong, M.D., Ph.D. is a Clinical Instructor at Vanderbilt University Medical Center in the Divisions of Allergy, Pulmonary, & Critical Care Medicine and Rheumatology & Immunology. She has a strong clinical background in both rheumatology and pulmonology with an excellent scientific foundation in chemical biology and translational immunology from both her Ph.D. studies and her post-doctoral research studies following clinical training. Her long-term career plan is to become a leading physician-scientist in inflammatory myositis focused on the use of cutting-edge technologies to identify disease pathogenesis and novel therapeutic targets. To achieve this, her immediate goal is to (1) learn the requisite bioinformatic techniques to independently analyze high-dimensional immunophenotypic and transcriptional profiles and integrate these profiles with clinical outcomes, and (2) apply molecular immunology techniques to determine dysregulated pathways in IIM-specific cell populations. Research Project: This proposal will study the underlying immunologic heterogeneity of IIM and identify associations between immune/transcriptional signatures and clinical characteristics. Dr. Wilfong will (1) identify immune signatures and transcriptional aberrancies in IIM using a cross-sectional IIM cohort and (2) correlate immune features with ILD progression in a longitudinal IIM cohort. She will also take a prior single-cell RNA- Seq finding and (3) perform mechanistic studies investigate how upregulation of the redox sensor TXNIP alters immunometabolism in Jo1+ anti-tRNA synthetase syndrome. Career Development: Dr. Wilfong’s career development plan integrates formal coursework with personalized training from her mentors and collaborators to: (1) master R programming to facilitate analysis of immunophenotypic and transcriptional datasets using cutting-edge analytic tools, (2) learn biostatistical principles necessary to appropriately correlate immunology findings to clinical phenotypes, (3) characterize cellular function using in vitro assays, and (4) develop the leadership and communication skills necessary to become a principal investigator who applies the scientific findings and methodologies from this K08 award towards a future translational immunology R01. Environment: VUMC is the ideal environment to foster Dr. Wilfong’s development as a leader in translational immunology and inflammatory myositis. Dr. Wilfong’s mentoring team includes experts in inflammatory myositis (Crofford/Aggarwal), immunometabolism (Rathmell), single-cell RNA-Seq (Kropski), and computational immunology (Georgiev). In addition to having the necessary mentors and equipment, 71.3% of Vanderbilt University Medical Center career development award recipients (n=236) have successfully received R level funding since 1999. Drs. Crofford and Rathmell have successfully trained many physician-scientists and will ensure that Dr. Wilfong becomes an independently funded physician scientist.