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

摘要 总的来说，这项提案旨在定义病毒组（真核病毒和噬菌体）的作用， 肾移植受者健康和BK疾病中的细菌微生物组。BK多瘤病毒相关 肾病（BKVAN）是肾移植失败的主要原因。虽然BKVAN的机制基础 尽管对BKVAN的进展知之甚少，但BK病毒血症是BKVAN最一致的替代标志物。其他的都是 了解病毒组和细菌微生物组如何影响肾移植中的健康和疾病。在 特别是，以前未表征的人类尿病毒组是我们对人类尿病毒组的理解中的一个重大差距。 人类微生物组。为了解决这个问题，我们将分析循环（血浆）病毒组在一个独特的纵向 肾移植受者队列，并评估其与免疫抑制和BK病毒血症的相关性。 此外，通过定义尿液病毒组和细菌微生物组，我们将获得前所未有的 有机会检查尿路中微生物组的相互作用。这将使我们能够定义小说 BK疾病和病毒组之间的相互作用，并探索微生物组 改变有助于肾移植受者的健康和疾病。这些发现可能会导致 更好地了解导致BK疾病的早期事件和监测功能性疾病的新方法 免疫活性水平通过个体的病毒组和微生物组。第99章与博士 大卫王（导师），博士赫伯特“跳过”维珍（共同导师）和博士丹尼尔布伦南（顾问）将支持 关键的培训和促进过渡，以解决这些问题，在一个新的研究领域的肾脏 移植

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.