Mentoring Junior Faculty: Viral hepatitis Clinical Research

描述（由申请人提供）：慢性病毒性肝炎是全球发病率和死亡率的主要原因。在过去的十年中，在慢性丙型肝炎和B型肝炎的新治疗方法的开发方面取得了重大进展，尽管这些疾病的管理策略仍在不断发展。超过一半的慢性丙型肝炎患者接受聚乙二醇干扰素和利巴韦林治疗可以达到持续的病毒学应答。然而，许多患者仍然未能实现永久性病毒根除或由于医学或心理社会共病而不是初始抗病毒治疗的候选者，这些共病是聚乙二醇干扰素和利巴韦林治疗的禁忌症。相比之下，用核苷类似物治疗慢性B型肝炎的耐受性更好，尽管疗效通常通过延长病毒抑制而不是永久治愈来衡量。对于这两种疾病，更好地理解对治疗的反应减弱的机制，开发优化的治疗方案和/或识别替代或新型药物至关重要。在Michael Fried博士的指导下，肝病项目非常积极地从事慢性病毒性肝炎治疗的研究。出于本申请的目的，我们将讨论一项由NCCAM/NIDDK资助的正在进行的I/II期研究，该研究调查了水飞蓟素（奶蓟）作为对常规抗病毒治疗无效的慢性丙型肝炎患者的替代治疗（U 01-AT 003560，SyNCH）。此外，我们将审查一项新的慢性B型肝炎研究，即由NIDDK资助的B型肝炎临床研究网络（U 01 DK 082867）。最后，我们将提出一个研究者发起的研究，利用新的方法来检查外周血单核细胞中的干扰素信号通路的详细概要。这些研究提供了指导计划的初级教师和研究员谁是积极参与他们的设计，实施和分析的骨干。如本申请所示，学员已被纳入这些研究活动，为他们提供了许多机会，在一个指导的环境中，发展研究技能，并坚持自己对个别项目的所有权。 公共卫生相关性：在K24指导奖的竞争性续签申请中，我将提供有关我在以患者为导向的研究方面的背景以及成功的临床研究和直接因该奖项而开发的综合指导计划的详细信息。我还将展示我对临床研究的持续奉献精神，以及我作为主要导师的一群才华横溢的初级研究人员。最后，我们将提供几个新的研究计划的例子，将继续确保有效的指导研究的机会，以及跨学科研究团队的发展计划，能够进行翻译研究。

DESCRIPTION (provided by applicant): Chronic viral hepatitis is a major global cause of morbidity and mortality. Over the last decade, significant progress has occurred in the development of new treatments for chronic hepatitis C and hepatitis B, although management strategy of these diseases continues to evolve. More than half of patients undergoing treatment with peginterferon and ribavirin for chronic hepatitis C can achieve a sustained virological response. However, numerous patients still fail to achieve permanent viral eradication or are not candidates for initial antiviral therapy due to medical or psychosocial comorbidities which are contraindications to peginterferon and ribavirin therapy. In contrast, treatments for chronic hepatitis B with nucleoside analogues, as examples, are better tolerated, although efficacy is generally measured by prolonged viral suppression, rather than permanent cure. For both these diseases, a better understanding of mechanisms of diminished response to therapy, development of optimized treatment regimens, and/or the identification of alternative or novel medications is of critical importance. The UNC Liver Diseases Program, under the direction of Dr. Michael Fried, is extremely active in pursuing studies that focus on treatment of chronic viral hepatitis. For the purposes of this application, we will discuss an ongoing phase I/II study, funded by NCCAM/NIDDK, that investigates silymarin (milk thistle) as an alternative treatment for patients with chronic hepatitis C who failed to respond to conventional antiviral therapy (U01-AT003560, SyNCH). Furthermore, we will review a new study for chronic hepatitis B, the Hepatitis B Clinical Research Network, funded by NIDDK (U01 DK082867). Finally, we will present a detailed synopsis of an investigator initiated study that examines interferon signaling pathways in peripheral blood mononuclear cells utilizing novel methodologies. These studies provide the backbone of the mentoring program for junior faculty and fellows who are actively involved in their design, implementation, and analysis. As demonstrated within this application, mentees have been integrated into these research activities which have provided them with numerous opportunities in a mentored environment within which to develop research skills and to assert their ownership of individual projects. PUBLIC HEALTH RELEVANCE: In this competing renewal application for the K24 Mentoring Award, I will provide detailed information regarding my background in patient-oriented research and the successful clinical research and integrated mentoring program that has been developed directly as a result of this award. I will also demonstrate my continued dedication to clinical research and to a diverse group of talented junior investigators for whom I serve as primary mentor. Finally, we will provide examples of several new research initiatives that will continue to ensure effective mentored research opportunities, as well as a plan for the development of interdisciplinary research teams capable of performing translational research studies.