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疗法反应的预测因素

• 批准号: 10132306
• 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/10132306
• 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; 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; risk stratification; 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.

本项目将评估对抗肿瘤坏死因子α（抗TNF）反应的预测性生物标志物 早期克罗恩病（CD）患者的治疗。候选人：此应用程序的主要目标是 支持Ryan Ungaro博士的职业发展，成为独立的以患者为导向的研究者， 针对炎症性肠病（IBD）患者的个性化药物。Ungaro博士的职业目标是成为 一个独立的研究人员和领导者的应用预测生物标志物和模型，以选择最好的 为近期确诊的IBD患者提供治疗和优化护理。Ungaro博士提议的培训活动是 在四个领域：1）先进的生物统计分析，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， Judy Cho博士，Charles Bronfman个性化医学研究所所长， 翻译基因组学，以及布鲁斯桑兹博士，胃肠科主任，谁拥有专业知识， IBD治疗的临床和转化研究，推动了许多开创性的研究， 抗TNF环境：西奈山伊坎医学院有着悠久的传统， 研究，是NIH资助的前20所医学院之一。西奈山分部 胃肠病学一直被认为是美国新闻和世界十大部门之一 是IBD研究和临床护理的国际领导者。研究：CD是一种慢性病， 影响胃肠道的进行性炎症。抗肿瘤坏死因子药物在很大程度上 改善了CD患者的治疗，然而，相当多的人对这些治疗没有反应。 这些药物非常昂贵并且具有潜在的致命副作用。CD的新药物类别是 为个性化医疗带来了机会。临床医生将需要工具来帮助决定 哪种药物对每个CD患者最有效。这一点在最近尤其重要。 确诊后的患者，有效的早期治疗可以减少远期并发症。因此我们 具体的目的是（1）确定外周血蛋白质组学标记物与抗- TNF（2）评估肠组织基因表达标志物与抗TNF应答的相关性，以及（3） 探索粘膜免疫结构和单细胞RNA抗TNF应答的预测能力 肠活检的测序（scRNASeq）。我们将研究最近诊断的CD患者（2年内）， 来自3个具有生物样本的前瞻性队列的IBD诊断）：基于人群的IBD初始队列，多中心 最近诊断的儿童CD患者队列和IBD患者的单中心生物储存库， 健康记录数据。此外，将招募一组最近诊断的CD患者进行scRNASeq 分析.在此奖项期间开发的一般方法和技能也可以应用于新的目标 这些研究为早期IBD治疗反应的生物标志物的未来研究奠定了基础。