Administrative Core

行政核心

• 批准号: 10684228
• 负责人: ARUL M CHINNAIYAN
• 金额: $ 41.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684228
• 关键词: Academic Medical Centers; Administrator; Agreement; Area; Biological Assay; Biological Markers; Biopsy; Clinical; Collaborations; Common Data Element; Communities; Data; Data Analyses; Data Coordinating Center; Development; Diagnostic tests; Disease; ERG gene; Early Detection Research Network; Early Diagnosis; Ensure; Funding; Future; Gene Fusion; Goals; Guidelines; Health; Industry; Informed Consent; Institution; Institutional Review Boards; Investigation; Knowledge; Laboratories; Leadership; Malignant Neoplasms; Malignant neoplasm of prostate; Manuscripts; Methods; Michigan; Mission; Monitor; Mutation; Network Infrastructure; Occupational activity of managing finances; PSA screening; Pathology; Populations at Risk; Principal Investigator; Procedures; Progress Reports; Prostate; Prostatic Diseases; RNA Splicing; Reporting; Research; Research Personnel; Resources; Sampling; Screening for Prostate Cancer; Specimen; Standardization; Structure of base of prostate; TMPRSS2 gene; Testing; Texas; Transcript; Translating; Translations; Travel; Universities; University resources; Untranslated RNA; Urine; Validation; Variant; Virginia; Vision; Work; antigen test; biobank; biomarker development; biomarker validation; cancer biomarkers; circular RNA; cohort; commercialization; curative treatments; data sharing; data submission; detection test; improved; industry partner; insertion/deletion mutation; medical schools; meetings; multidisciplinary; next generation; novel; novel diagnostics; novel marker; operation; personalized risk prediction; programs; protocol development; screening; serum PSA; shared decision making; specific biomarkers; success; transcriptome sequencing; transcriptomics; translational goal; urinary; validation studies

Project Summary/Abstract This application proposes the formation of the Michigan-Vanderbilt University Medical Center (VUMC) EDRN Biomarker Characterization Center (BCC). This BCC represents a collaborative, multi-disciplinary team of academic (University of Michigan (U-M) and VUMC) and industry (LynxDx) partners focused on discovering, developing, and scaling clinical-grade assays for the early detection of aggressive prostate cancer. Through previous EDRN efforts, our team characterized multiple important prostate cancer biomarkers, most notably the TMPRSS2-ETS gene fusions. Through collaboration with an EDRN Clinical Validation Center (CVC; Dr. Sanda PI), we developed, validated, and clinically implemented MyProstateScore (MPS), an early detection test incorporating urine quantification of two prostate cancer-specific transcripts—the TMPRSS2:ERG gene fusion and the long non-coding RNA (lncRNA) PCA3. Introduced in our CLIA laboratory, MPS informs shared decision making after PSA testing based on individualized risk predictions of aggressive prostate cancer on biopsy. Here, pairing the cancer-specific components of the MPS test with recent discovery of high-grade cancer-specific biomarkers, we outline the development, optimization, and clinical validation of the next generation of diagnostic tests – capable of reliably, selectively detecting potentially lethal cancers that stand to benefit from early curative treatment. Our Biomarker Developmental Laboratory (BDL) will employ the experimental platform, MPS-SEQ, for capture RNA-seq analysis of urine samples to detect aggressive prostate cancer transcripts, lncRNAs, circular RNAs, fusion transcripts, mutations, indels, and splice variants. Our Biomarker Reference Laboratory (BRL) will in parallel develop a clinical grade urine assay, MPS-50, for the multiplex QPCR analysis of up to 50 amplicons. While the first 50 amplicons of MPS-50 have already been nominated, future improvements of the assay content and platform will be informed by work carried out in our BDL. To fuel these studies, our BCC has identified urine biospecimen cohorts collected under rigorous standard operating procedures in compliance with PRoBE criteria including the Michigan Prostate SPORE, Emory University, the Center for Prostate Disease Research, University of Texas San Antonio Health, Eastern Virginia Medical School, and VUMC/Meharry Medical College. The overall Aims of this BCC serve to develop, assess, and optimize MPS-SEQ and MPS-50 for identifying high-grade prostate cancer in diverse at-risk populations. Our BRL will also focus on standardizing clinically-validated biomarker assays for consistent and reliable use in accordance with CLIA/CAP guidelines at the U-M Center for Translational Pathology in order to facilitate network consortium studies and at LynxDx in order to scale, commercialize, and obtain FDA approvals. As recognized by the EDRN, novel biomarkers specific for aggressive prostate cancer are urgently needed. Importantly, our mission and efforts extend beyond our BCC and prostate cancer, as we actively participate in the EDRN biomarker community and support continued collaborative efforts with other BCCs and CVCs to advance the overall EDRN mission.

项目概要/摘要 该申请提议成立密歇根-范德比尔特大学医学中心 (VUMC) EDRN 生物标志物表征中心 (BCC)。该 BCC 代表了一个协作的、多学科的团队 学术（密歇根大学 (U-M) 和 VUMC）和工业 (LynxDx) 合作伙伴专注于发现、 开发和扩展用于早期检测侵袭性前列腺癌的临床级检测。通过 在之前的 EDRN 工作中，我们的团队对多种重要的前列腺癌生物标志物进行了表征，最值得注意的是 TMPRSS2-ETS 基因融合。通过与 EDRN 临床验证中心（CVC；Sanda 博士）合作 PI），我们开发、验证并临床实施了 MyProstateScore (MPS)，这是一种早期检测测试 结合两种前列腺癌特异性转录本的尿液定量——TMPRSS2:ERG 基因融合 和长非编码RNA (lncRNA) PCA3。 MPS 在我们的 CLIA 实验室中引入，可告知共同决策 根据活检中侵袭性前列腺癌的个体化风险预测进行 PSA 测试。这里， 将 MPS 测试的癌症特异性成分与最近发现的高级癌症特异性成分配对 生物标志物，我们概述了下一代诊断的开发、优化和临床验证 测试——能够可靠、选择性地检测潜在致命的癌症，这些癌症有望从早期治疗中受益 治疗。我们的生物标志物发育实验室（BDL）将采用实验平台MPS-SEQ， 用于捕获尿液样本的 RNA-seq 分析，以检测侵袭性前列腺癌转录物、lncRNA、 环状 RNA、融合转录本、突变、插入缺失和剪接变体。我们的生物标志物参考实验室 (BRL) 将同时开发临床级尿液检测 MPS-50，用于最多 50 个样本的多重 QPCR 分析 扩增子。虽然 MPS-50 的前 50 个扩增子已经被提名，但未来的改进 检测内容和平台将通过我们的 BDL 中开展的工作来了解。为了推动这些研究，我们的 BCC 已 确定了按照严格的标准操作程序收集的尿液生物样本队列，符合 PRoBE 标准包括密歇根前列腺 SPORE、埃默里大学前列腺疾病中心 研究机构：德克萨斯大学圣安东尼奥健康分校、东弗吉尼亚医学院和 VUMC/Meharry 医学院。该 BCC 的总体目标是开发、评估和优化 MPS-SEQ 和 MPS-50 用于识别不同高危人群中的高级别前列腺癌。我们的 BRL 还将重点关注标准化 根据 CLIA/CAP 指南进行临床验证的生物标志物测定，以实现一致和可靠的使用 密歇根大学转化病理学中心，以促进网络联盟研究和 LynxDx 为了规模化、商业化并获得 FDA 批准。正如 EDRN 所认识到的，新型生物标记物具有特异性 迫切需要治疗侵袭性前列腺癌。重要的是，我们的使命和努力超出了我们的 BCC 和前列腺癌，因为我们积极参与 EDRN 生物标志物社区并持续提供支持 与其他 BCC 和 CVC 合作，推进 EDRN 的整体使命。