Bay Area Hepatitis C Cooperative Research Center

湾区丙型肝炎合作研究中心

基本信息

批准号：
8666621
负责人：
JAMES C RYAN
金额：
$ 72.52万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8666621
关键词：
Accounting Acute Acute Hepatitis C Address Aftercare Antibodies Antigen-Presenting Cells Antigens Antiviral Agents Antiviral Response Applications Grants Area B-Lymphocytes Biological Biology Blood CCR5 gene CD94 Antigen California Caring Case-Control Studies Cell physiology Cells Cessation of life Chronic Chronic Disease Chronic Hepatitis C Cirrhosis Clinic Clinical Clinical Investigator Clinical Research Clinical Sciences Clinical Trials Combined Modality Therapy Complex Computerized Medical Record Consult Cytokine Network Pathway Data Data Analyses Data Set Databases Dendritic Cells Development Enrollment Ensure Epidemiology Ethnic group Family Frequencies General Hospitals General Population Genetic Polymorphism Genotype Goals HLA Antigens Hepatitis C Hepatitis C Antibodies Hepatitis C virus Hispanics Histocompatibility Antigens Class II Immune response Immune system Immunity Immunologist Individual Infection Inflammatory Institutes Interferon-alpha Interferons Laboratories Lead Learning Ligands Literature Liver Macrophage Activation Malignant neoplasm of liver Mediating Medical center Memory Morbidity - disease rate NK Cell Activation Natural Immunity Natural Killer Cells Outcome Patients Phenotype Plasma Play Population Process Prospective Studies Recruitment Activity Regimen Registries Research Research Infrastructure Research Institute Resources Ribavirin Role Sampling San Francisco Services Site Source Specimen System T-Lymphocyte Testing Time Translational Research Treatment Failure Treatment Protocols United States Universities Up-Regulation Veterans Viral Viral Load result Viral hepatitis Virus Virus Diseases Work adaptive immunity arm base case control cell motility chemokine receptor clinical epidemiology cohort cytokine cytotoxic cytotoxicity data management data sharing experience immunoglobulin receptor improved insight liver biopsy memory acquisition monocyte mortality multidisciplinary neutralizing antibody novel peripheral blood prospective racial and ethnic receptor research study response standard of care systems research treatment response

项目摘要

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) infection is the leading cause of liver-related morbidity and mortality in the United States. Although spontaneous clearance of virus occurs in some who are infected and current treatment regimens result in sustained virologic response in others, there remains an unacceptably high frequency of treatment failure. To better understand the contribution of the immune response to viral clearance, we propose the creation of a Bay Area Hepatitis C Cooperative Research Center. The goals of this Center are to define the biology of the innate and adaptive immune responses to HCV in the setting of chronic infection, to understand how these responses are modulated by treatment, and to discern which parameters of the immune response are associated with (and possibly predictive of) an effective antiviral response to therapy. The Center will assemble a strong multidisciplinary team comprised of immunologists and clinical investigators at multiple sites in the San Francisco Bay Area, including three different sites associated with the University of California at San Francisco (UCSF) (San Francisco General Hospital, UC Medical Center, and the San Francisco Veterans Affairs Medical Center) as well as with the California Pacific Medical Center, the Blood Systems Research Institute, and Kaiser Permanente (KP) of Northern California. A Clinical Epidemiology Core (led by Drs. Michele Manos of KP Division of Research and Norah Terrault of UCSF) will develop and manage (a) a retrospective case-control cohort of 200 subjects who did or did not respond to standard-of-care therapy, and (b) a prospective cohort of treatment-naive subjects who will be followed before and after the initiation of therapy. In Project 1 (led by Drs. James Ryan and Lewis Lanier of UCSF), the contribution of innate immunity to treatment response will be studied. Concomitantly, and using the same set of patient samples. Project 2 (led by Drs. Dennis Hartigan- O'Connor and Joseph McCune of UCSF) will analyze the role of adaptive T and B cell responses against HCV. Coordinated analyses of data obtained in both Projects will permit tests of discrete hypotheses that speak to interactions between the innate and adaptive systems. The activities of the Center will be organized through an Administrative Core, directed by the PI (Dr. McCune). We anticipate that the efforts of this Center will provide data that can inform treatment decisions in the short term and contribute to development of better and more generally applicable therapies for chronic HCV disease in the longer term.

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是美国肝有关的发病率和死亡率的主要原因。尽管一些感染的人会自发清除病毒，并且当前的治疗方案会导致其他病毒的持续病毒反应，但治疗衰竭的频率仍然很高。为了更好地了解免疫反应对病毒清除率的贡献，我们提议创建乙型肝炎合作研究中心。该中心的目标是在慢性感染的情况下定义对HCV的先天和适应性免疫反应的生物学，以了解这些反应是如何通过治疗调节的，并辨别免疫反应的哪些参数与有效的抗病毒治疗反应有关（并可能预测）对治疗的有效抗体反应。 The Center will assemble a strong multidisciplinary team comprised of immunologists and clinical investigators at multiple sites in the San Francisco Bay Area, including three different sites associated with the University of California at San Francisco (UCSF) (San Francisco General Hospital, UC Medical Center, and the San Francisco Veterans Affairs Medical Center) as well as with the California Pacific Medical Center, the Blood Systems Research Institute, and Kaiser北加州的永久（KP）。临床流行病学核心（由KP研究部门的Michele Manos博士和UCSF的Norah Terrault博士领导）将开发和管理（a）回顾性的病例对照组，由200名受试者组成的病例对照组，他们对标准的护理疗法做出了反应或不反应（b）对治疗方法的前瞻性对象，这些受试者将对以前的治疗和后期进行治疗。在项目1（由UCSF的James Ryan博士和Lewis Lanier博士领导）中，将研究先天免疫对治疗反应的贡献。同时使用相同的患者样品。项目2（由UCSF的Dennis Hartigan-O'Connor博士和Joseph McCune领导）将分析适应性T和B细胞反应对HCV的作用。在两个项目中获得的数据的协调分析将允许对先天和自适应系统之间相互作用的离散假设进行测试。该中心的活动将通过PI（McCune博士）指导的行政核心组织。我们预计，该中心的努力将提供可以在短期内为治疗决定提供信息的数据，并有助于长期开发更好，更普遍适用的慢性HCV疾病疗法。