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The Virome and Microbiome in Health and BK Disease of Kidney Transplant Patients

肾移植患者健康和 BK 病中的病毒组和微生物组

基本信息

批准号：
9565563
负责人：
Efrem Lim
金额：
$ 24.9万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
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：
2017-09-15 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9565563
关键词：
Acute Address Adult Affect Age Archives BK Virus Bacteria Bacteriophages Climacteric Complex DNA Viruses Diabetes Mellitus Disease Ecology Enrollment Event Failure Family Foundational Skills Graft Survival Health Human Human Microbiome Immune response Immune system Immunity Immunocompetence Immunosuppression Immunosuppressive Agents Individual Infant Infection Intervention Kidney Kidney Diseases Kidney Transplantation Laboratories Lead Light Liver Cirrhosis Longitudinal cohort Medicine Mentors Metagenomics Modeling Monitor Nature Pathologic Pathology Patient Monitoring Patients Phase Physiology Plasma Protocols documentation RNA Viruses Research Role Specimen Surrogate Markers System Techniques Training Training and Education Translations Transplant Recipients Universities Urinary tract Urine Viral Viral Load result Viremia Virus Washington Work allograft rejection bacterial community bacteriome career development cohort dark matter effective therapy human disease human virome immune activation individualized prevention infancy microbiome microbiome alteration microorganism multidisciplinary next generation sequencing novel novel strategies novel virus precision medicine prevent programs response sample collection urinary virome

项目摘要

Abstract Overall, this proposal seeks to define the role of the virome (eukaryotic viruses and bacteriophages) and bacterial microbiome in the health and BK disease of kidney transplant recipients. BK polyomavirus-associated nephropathy (BKVAN) is a major cause of kidney transplant failure. While the mechanistic basis for BKVAN progression is poorly understood, BK viremia is the most consistent surrogate marker for BKVAN. Little else is known about how the virome and bacterial microbiome impacts health and disease in kidney transplantation. In particular, the previously uncharacterized human urinary virome is a significant gap in our understanding of the human microbiome. To address this, we will analyze the circulatory (plasma) virome in a unique longitudinal cohort of kidney transplant recipients and assess their correlates with immunosuppression and BK viremia. Additionally, by defining the urinary virome and bacterial microbiome, we will have an unprecedented opportunity to examine microbiome interactions in the urinary tract. This will allow us to define novel interactions between BK disease and the virome, and explore the mechanisms by which microbiome alterations contribute to the health and disease of kidney transplant recipients. These findings could lead to a better understanding of the early events leading up to BK disease and a novel approach to monitor functional immunocompetence levels through the individual’s virome and microbiome. The mentored K99 phase with Dr. David Wang (Mentor), Dr. Herbert “Skip” Virgin (Co-mentor) and Dr. Daniel Brennan (Advisor) will support critical training and facilitate the transition to address these questions in a new research field of kidney transplantation.

摘要