An individualized network medicine infrastructure for precision cardio-oncology

用于精准心脏肿瘤学的个性化网络医学基础设施

基本信息

批准号：
9371272
负责人：
Feixiong Cheng
金额：
$ 8.58万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9371272
关键词：
Address Adverse effects Adverse event Algorithmic Analysis Algorithms Animal Model Animals Area Award Awareness Big Data Biological Assay Biological Markers Biology Cancer Etiology Cancer Patient Cancer Survivor Cardiac Cardiac Myocytes Cardiotoxicity Cardiovascular system Caring Cells Combined Modality Therapy Comorbidity Complex Computational algorithm Coronary Arteriosclerosis Dana-Farber Cancer Institute Data Development Diagnosis Discipline Disease Drug Interactions Drug Targeting Educational Curriculum Environment Evaluation Gene Proteins Goals Guidelines Health Insurance Heart failure Hereditary Disease Heterogeneity Hospitals Human Immune checkpoint inhibitor Influentials Knowledge Malignant Neoplasms Medicine Mentors Monitor Myocardial dysfunction Network-based Pathway interactions Patient Care Patients Pharmaceutical Preparations Pharmacoepidemiology Pharmacology Phase Play Polypharmacy Positioning Attribute Prevention Principal Investigator Productivity Prognostic Marker Program Development Proteasome Inhibitor Proteins Reporting Research Research Infrastructure Research Personnel Research Training Risk Role Science Surrogate Markers System Systems Biology Techniques Therapeutic Therapeutic Agents Training United States Universities Vocational Guidance Woman base big biomedical data biomedical informatics cancer care cancer cell cancer therapy career career development computerized tools cost drug development drug discovery genetic variant genome-wide improved outcome individual patient innovation kinase inhibitor molecular oncology new therapeutic target next generation sequencing novel novel therapeutics oncology patient oriented pharmacodynamic biomarker precision medicine predictive marker prevent programs screening tool development training opportunity transcriptome treatment strategy

项目摘要

The growing awareness of cardiac dysfunction by cancer treatment has led to the emerging field of cardio- oncology. However, there are no guidelines in terms of how to prevent and treat the new cardiotoxicity in cancer survivors due to the limited experimental assays. Network medicine – a discipline that seeks to redefine disease and therapeutics from an integrated perspective using systems biology and network science – offers a non-invasive way to identify actionable biomarkers for cardio-oncology. This five-year career development program will develop state-of-the-art systems pharmacology and network medicine approaches in cardio- oncology that focuses on screening, monitoring, and treating cancer survivors with cardiac dysfunction resulting from cancer treatment for facilitating the career goals to the principal investigator (PI), Dr. Feixiong Cheng. With this application, the PI will adhere to a rigorous mentored training curriculum in Northeastern University, Dana-Farber Cancer Institute, and Harvard’s Brigham and Women's Hospital (BWH). The PI’s mentor, Dr. Albert-Laszlo Barabasi, one of the world’s leading experts in the field of network science, has strong collaborative relations with his co-mentors, Drs. Joseph Loscalzo and Sebastian Schneeweiss, in BWH. Dr. Loscalzo, an influential cardiologist, will provide the PI with cardiovascular biology training, career guidance, and scientific advice on the execution of the proposed research plan. Dr. Schneeweiss, a premier pharmacoepidemiologist, will provide the PI with training on applying computationally intensive algorithms for analyzing patient longitudinal big data. This program proposes two specific aims: 1) Development of a state-of- the-art systems pharmacology approach, namely genome-wide positioning systems drug network (GPSDnet) algorithm, to illuminate the landscape of cardiotoxicity to various cancer agents (K99) - The central, unifying hypothesis of GPSDnet is that an integrated, mechanism-based, network approach which incorporates next- generation sequencing data, drug-target networks, drug-induced transcriptome, the human interactome, along with adverse event reports from the FDA’s Adverse Event Reporting System and patient longitudinal data, will prove a novel and effective way for evaluation of cardiotoxicity for current cancer therapies (e.g., multitargeted kinase inhibitors) and new therapies (e.g., immune checkpoint inhibitors); 2) Cardio-oncology perturbation, diagnosis, prevention, and patient care (R00) - The Aim 2 will emphasize the use of network medicine techniques to identify actionable biomarkers (e.g., comorbidity network modules shared by cancer cells and cardiovascular cells/systems) for advancing the characterization of cardio-oncology heterogeneity, thereby achieving the goal of coordinated, patient-centered strategies for treatment and long-term cardiovascular care (e.g., heart failure and coronary artery disease) for cancer survivors. In summary, approval of this K99 award will be invaluable in establishing Dr. Cheng as an independent investigator by exploiting the promise of precision medicine that is in need of experts specializing in network medicine for cardio-oncology.

人们对癌症治疗引起的心脏功能障碍的认识不断提高，导致了心脏领域的新兴领域然而，目前还没有关于如何预防和治疗新的心脏毒性的指南。网络医学是一门寻求重新定义的学科。使用系统生物学和网络科学从综合角度看待疾病和治疗——提供了以非侵入性方式识别心脏肿瘤学的可行生物标志物。这五年的职业发展。该计划将开发心脏领域最先进的系统药理学和网络医学方法专注于筛查、监测和治疗患有心脏功能障碍的癌症幸存者的肿瘤学为促进首席研究员 (PI) Feixiong 博士实现职业目标而进行的癌症治疗通过此申请，PI 将遵守东北大学严格的指导培训课程。大学、达纳法伯癌症研究所和哈佛大学布莱根妇女医院 (BWH)。导师 Albert-Laszlo Barabasi 博士是网络科学领域世界领先的专家之一。与他在 BWH 的共同导师 Joseph Loscalzo 博士和 Sebastian Schneeweiss 博士建立了密切的合作关系。 Loscalzo 博士是一位颇具影响力的心脏病专家，他将为 PI 提供心血管生物学培训、职业指导、以及关于执行拟议研究计划的科学建议。药物流行病学家将为 PI 提供应用计算密集型算法的培训该计划提出了两个具体目标：1）发展现状。最先进的系统药理学方法，即全基因组定位系统药物网络（GPSDnet）算法，阐明各种癌症药物的心脏毒性 (K99) - 中央的、统一的 GPSDnet 的假设是一种集成的、基于机制的网络方法，其中包含下一步：一代测序数据、药物靶标网络、药物诱导转录组、人类相互作用组等借助 FDA 不良事件报告系统的不良事件报告和患者纵向数据，将证明了一种新颖且有效的方法来评估当前癌症疗法的心脏毒性（例如，多靶点 2) 心脏肿瘤学扰动，诊断、预防和患者护理 (R00) - Aim 2 将强调网络医学的使用识别可操作的生物标志物的技术（例如，癌细胞共享的共病网络模块和心血管细胞/系统），以推进心脏肿瘤异质性的表征，从而实现协调的、以患者为中心的治疗和长期心血管护理策略的目标（例如，心力衰竭和冠状动脉疾病）癌症幸存者总而言之，批准该 K99 奖项。通过利用以下承诺，对于将程博士确立为独立研究者将具有无价的价值精准医疗需要专门从事心血管肿瘤网络医学的专家。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors.

DOI：
10.1186/s40959-021-00106-x
发表时间：
2021-05-28
期刊：
Cardio-oncology (London, England)
影响因子：
0
作者：
Lal JC;Brown SA;Collier P;Cheng F
通讯作者：
Cheng F

Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

定量和系统药理学。

DOI：
10.1021/acs.jcim.7b00216
发表时间：
2017-11-27
期刊：
Journal of chemical information and modeling
影响因子：
5.6
作者：
Fang J;Wu Z;Cai C;Wang Q;Tang Y;Cheng F
通讯作者：
Cheng F

In Silico Insights into Protein-protein Interaction Disruptive Mutations in the PCSK9-LDLR complex.

在计算机上深入了解 PCSK9-LDLR 复合物中蛋白质-蛋白质相互作用破坏性突变。

DOI：
10.3390/ijms21051550
发表时间：
2020
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Martin,WilliamR;Lightstone,FeliceC;Cheng,Feixiong
通讯作者：
Cheng,Feixiong

Machine Learning-Based Risk Assessment for Cancer Therapy-Related Cardiac Dysfunction in 4300 Longitudinal Oncology Patients.

DOI：
10.1161/jaha.120.019628
发表时间：
2020-12
期刊：
Journal of the American Heart Association
影响因子：
5.4
作者：
Zhou Y;Hou Y;Hussain M;Brown SA;Budd T;Tang WHW;Abraham J;Xu B;Shah C;Moudgil R;Popovic Z;Cho L;Kanj M;Watson C;Griffin B;Chung MK;Kapadia S;Svensson L;Collier P;Cheng F
通讯作者：
Cheng F

Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.