Assessing Predictors of Response to Anti-Tumor Necrosis Alpha Therapy in Early Crohns Disease

评估早期克罗恩病抗肿瘤坏死α疗法反应的预测因子

• 批准号: 9897566
• 负责人: RYAN UNGARO
• 金额: $ 18.93万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897566
• 关键词: Advisory Committees; Affect; American; Anti-Tumor Necrosis Factor Therapy; Apoptosis; Architecture; Area; Award; Biological; Biological Markers; Biometry; Biopsy; Blood; Blood Proteins; Caring; Cellular Immunology; Characteristics; Child; Chronic; Clinical; Clinical Data; Country; Crohn' s disease; Data; Deposition; Diagnosis; Disease; Disease Progression; Drug toxicity; Early treatment; Environment; Exposure to; Extracellular Matrix; Failure; Funding; Gastroenterology; Gastrointestinal tract structure; Gene Expression; Gene Expression Profile; Genomics; Goals; Grant; Immune; Immunogenetics; Immunologic Monitoring; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Institutes; Insurance; International; Intestinal Fistula; Intestines; Investigation; Laboratories; Leukocytes; Link; Longitudinal cohort; Mentors; Mentorship; Modeling; Molecular; Mucous Membrane; Necrosis; Oceans; Patient risk; Patients; Pattern; Pediatric Crohn' s disease; Pharmaceutical Preparations; Positioning Attribute; Process; Prospective cohort; Proteomics; Registries; Reporting; Research; Research Personnel; Resistance; Risk; Risk stratification; Sampling; Serum; Silicon Dioxide; Statistical Data Interpretation; TNF gene; Techniques; Therapeutic; Tissue Model; Tissues; Training; Training Activity; United States National Institutes of Health; Work; biobank; biomarker development; candidate marker; career; career development; clinical biomarkers; clinical care; cohort; cost; disability; disorder risk; health record; improved; individualized medicine; innovation; large bowel Crohn' s disease; longitudinal analysis; medical schools; microbial; news; patient oriented; peripheral blood; personalized medicine; population based; potential biomarker; predicting response; predictive marker; predictive modeling; recruit; response; response biomarker; side effect; single-cell RNA sequencing; skills; tissue biomarkers; tool; transcriptome sequencing; translational genomics; treatment optimization; treatment response; tumor; tumor necrosis factor-alpha inhibitor

This project will evaluate predictive biomarkers of response to anti-tumor necrosis factor alpha (anti-TNF) therapy in early Crohn's disease (CD) patients. Candidate: The primary objective of this application is to support Dr. Ryan Ungaro's career development into an independent patient-oriented investigator in the field of personalized medicine for inflammatory bowel disease (IBD) patients. Dr. Ungaro's career goal is to become an independent researcher and leader in the application of predictive biomarkers and models to select the best treatment and optimize care for recently diagnosed IBD patients. Dr. Ungaro's proposed training activities are in four areas: 1) advanced biostatistical analysis, 2) predictive biomarker analysis, 3) computational genomics, and 4) principles of immune monitoring. To achieve this, he has assembled a mentoring and advisory team led by Dr. Judy Cho, Director of the Charles Bronfman Institute of Personalized Medicine and an expert in translational genomics, and Dr. Bruce Sands, Chief of the Division of Gastroenterology, who has expertise in clinical and translational investigation of IBD therapeutics, having driven much of the pioneering research in anti-TNFs. Environment: The Icahn School of Medicine at Mount Sinai has a strong tradition of outstanding research and is one of the top 20 medical schools in NIH funding. The Mount Sinai Division of Gastroenterology is consistently considered one of the top 10 divisions in the country by US News and World Report and is an international leader in IBD research and clinical care. Research: CD is a chronic, progressive, inflammatory condition affecting the gastrointestinal tract. Anti-TNF medications have vastly improved the treatment of CD patients, however a significant number of individuals do not respond to these agents which are very costly and have potentially fatal side effects. New classes of medications for CD are being released bringing the opportunity for personalized medicine. Clinicians will need the tools to help decide which medication will work best for each individual CD patient. This will be particularly important in recently diagnosed patients since effective early treatment can decrease long-term complications. Therefore our specific aims are to (1) determine the association of peripheral blood proteomic markers with response to anti- TNF (2) assess the association of intestinal tissue gene expression markers with anti-TNF response and (3) explore the mucosal immune architecture and predictive capacity for anti-TNF response of single cell RNA sequencing (scRNASeq) of intestinal biopsies. We will study recently diagnosed CD patients (within 2 years of diagnosis) from 3 prospective cohorts with biosamples: a population-based IBD inception cohort, a multi-center cohort of recently diagnosed pediatric CD patients, and a single-center biorepository of IBD patients linked to health records data. In addition, a cohort of recently diagnosed CD patients will be recruited for scRNASeq analysis. The general approaches and skills developed during this award can also be applied to new targeted medications and form the basis for future research on biomarkers of treatment response in early IBD.

该项目将评估对抗肿瘤坏死因子α（抗TNF）的反应的预测生物标志物 早期克罗恩病（CD）患者的治疗。候选人：本申请的主要目的是 支持Ryan Ungaro博士的职业发展，成为一名以患者为导向的研究者 炎症性肠病（IBD）患者的个性化医学。 Ungaro博士的职业目标是成为 独立的研究人员和领导者在应用预测生物标志物和模型中选择最佳的领导者 治疗并优化最近诊断出的IBD患者的护理。 Ungaro博士提议的培训活动是 在四个领域：1）高级生物统计分析，2）预测生物标志物分析，3）计算基因组学， 4）免疫监测的原则。为了实现这一目标，他组建了一个指导和咨询团队 Charles Bronfman个性化医学研究所主任朱迪·乔（Judy Cho）博士，专家 转化基因组学和胃肠病学系负责人布鲁斯·桑兹（Bruce Sands）博士，他在 IBD治疗剂的临床和翻译研究已经推动了许多开创性研究 抗TNF。环境：西奈山的伊坎医学院具有杰出的良好传统 研究，是NIH资助的前20名医学院之一。西奈山师 美国新闻和世界一致认为胃肠病学被认为是该国十大分区之一 报告，是IBD研究和临床护理的国际领导者。研究：CD是慢性 渐进性，炎症状况影响胃肠道。抗TNF药物已大大 改善了CD患者的治疗 代理非常昂贵并且具有潜在的致命副作用。新的CD药物类别是 被发布带来个性化医学的机会。临床医生将需要这些工具来帮助决定 哪种药物最适合每个CD患者。这将在最近尤其重要 诊断为患者，因为有效的早期治疗会减少长期并发症。因此我们的 具体目的是（1）确定外周血蛋白质组学标记与抗抗反应的关联 TNF（2）评估肠道组织基因表达标记与抗TNF反应的关联和（3） 探索单细胞RNA抗TNF反应的粘膜免疫结构和预测能力 肠活检的测序（scrnaseq）。我们将研究最近诊断为CD患者（在2年内 诊断）与生物样本的3个前瞻性队列：一个基于人群的IBD Inception队列，一个多中心 最近诊断为儿科CD患者的队列和IBD患者的单中心生物座 健康记录数据。此外，将招募一组最近被诊断的CD患者进行SCRNASEQ 分析。该奖项期间开发的一般方法和技能也可以应用于新的目标 在IBD早期治疗反应生物标志物的未来研究的基础。