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.

该项目将评估抗肿瘤坏死因子α (anti-TNF)反应的预测性生物标志物。