Mentoring Clinical and Translational Patient-Oriented Research in Staphylococci

描述(申请人提供)：自从我十年前完成临床培训以来，我的研究一直围绕着这样一个问题：为什么金黄色葡萄球菌感染的患者有些做得好，而有些患者做得不好？最近，作为一名内科医生和科学家，我走到了一个明显的十字路口。我已经建立了一个资金充足、研究活动广泛的研究基础设施。虽然专注于金黄色葡萄球菌，但它涵盖了从生物体发病机制的基础科学，到宿主遗传易感性，再到疾病的临床特征。我所处的体制环境使我能够利用其培训和受训人员的大量资源。我还展示了为各种各样的初级研究人员提供指导的记录。出于这些原因，我认为对我来说，获得K24分至关重要，这样我就可以专注于研究及其指导，并避免医生/科学家在临床上过度投入的常见陷阱。因此，这项建议的总体目标是通过培训下一代临床医生-科学家在葡萄球菌临床和面向患者的翻译研究方面提高我的指导技能。指导技能不是与生俱来的；它们可以而且应该是后天学习的。我将通过几种方式发展我的指导专长。首先，我的指导进展将得到由资深研究人员和导师组成的咨询委员会的定期正式审查。接下来，我将创建“生涯中期导师计划”。与上面概述的高层意见不同，该计划将通过将杜克大学职业生涯中期的K24学员聚集在一起讨论常见的指导问题，来追求“点对点”的方法来指导技能发展。最后，我将通过参加国家CTSA公爵辅导小组委员会，参与国家一级的辅导。从科学上讲，我将通过追求两个具体目标来促进我的指导计划，这两个目标包含了我的研究平台的广度。每个目标都包括几个不同的项目，重点是以患者为导向的葡萄球菌研究。这些项目将作为支持我的指导计划的假设检验科学。具体目标1，指导临床以患者为导向的葡萄球菌研究，将通过实施3个单独项目来实现：一个项目侧重于导管相关葡萄球菌菌血症治疗算法的随机多国试验，以及另外两个项目使用大型葡萄球菌感染临床数据库。具体目标2，指导面向患者的葡萄球菌翻译研究，将通过实施涉及金黄色葡萄球菌感染的细菌和宿主遗传决定因素的几个项目来实现。我的长期目标是创建一个多学科项目，专注于葡萄球菌的临床和翻译POR。通过扩大我的研究计划的广度，K24将促进我朝着这一目标取得进展，并将有助于为下一代临床医生和科学家对抗这种持久的病原体做好准备。 这项建议与公共卫生的相关性：这项K24建议与美国公众的健康高度相关，因为它旨在为下一代临床医生-科学家对抗金黄色葡萄球菌做准备。金黄色葡萄球菌是困扰美国公众的主要病原体之一。金黄色葡萄球菌的感染率和耐药率都在上升。对现有抗生素耐药的临床金黄色葡萄球菌分离株的鉴定表明，病原体可能对目前批准的所有治疗方法都具有抗药性。这项建议旨在通过指导年轻的研究人员对葡萄球菌的临床和面向患者的翻译研究来提高我们对这种持久性病原体的理解。

DESCRIPTION (provided by applicant): Since the completion of my clinical training a decade ago, my research has focused on the question, "Why do some patients with Staphylococcus aureus infection do well, while others do poorly?" Recently, I have come to a distinct crossroad as a physician-scientist. I have erected a research infrastructure which is well-funded and has a breadth of research activities. While focused on S. aureus, it spans from the basic science of the organism's pathogenesis, to host genetic susceptibility, to direct clinical features of disease. I am in an institutional environment which allows me to tap into its substantial resources of training and trainees. I have also demonstrated a track record in providing mentorship to a wide variety of beginning researchers. For these reasons, I believe it is critically important for me to earn a K24 so I can focus on research and its mentoring and avoid the common pitfall of the physician/scientist who becomes clinically overcommitted. Thus, the overall goal of this proposal is to improve my mentoring skills by training the next generation of clinician-scientists in clinical and translational patient oriented research in the staphylococci. Mentoring skills are not innate; they can and should be learned. I will develop my mentoring expertise in several ways. First, my mentoring progress will receive regular formal review from an Advisory Board of senior researchers and mentors. Next, I will create the "Mentoring Mid-Career Mentors Program". In contrast to the senior-level input outlined above, this program will pursue a "peer to peer" approach to mentor skills development by bringing together Duke's mid-career K24 recipients to discuss common mentoring issues. Finally, I will participate in mentoring on a national level by involvement in the National Subcommittee on Mentoring of the Duke CTSA. Scientifically, I will facilitate my mentoring plan by pursuing two Specific Aims that incorporate the breadth of my research platform. Each Aim includes several distinct projects focused on patient oriented research of staphylococci. These projects will serve as the hypothesis-testing science that undergirds my mentoring plan. Specific Aim 1, mentoring clinical patient oriented research in staphylococci, will be accomplished by pursuing 3 individual projects: one project focused on a randomized, multinational trial of a treatment algorithm for catheter-related staphylococcal bacteremia, and two other projects employing large clinical databases of staphylococcal infections. Specific Aim 2, mentoring translational patient-oriented research in staphylococci, will be accomplished by pursuing several projects involving bacterial and host genetic determinants of S. aureus infection. My long-term objective is to create a multidisciplinary program that focuses on clinical and translational POR of staphylococci. By expanding the breadth of my research program, a K24 would enhance my progress towards this goal, and would help to prepare the next generation of clinician-scientists to confront this persistent pathogen. RELEVANCE OF THIS PROPOSAL TO PUBLIC HEALTH: This K24 proposal is highly relevant to the health of the American Public, as it aims to prepare the next generation of clinician-scientists to confront Staphylococcus aureus. S. aureus is one of the leading pathogens plaguing the American public. Rates of both infections and antibiotic resistance in S. aureus are increasing. The identification of clinical S. aureus isolates resistant to available antibiotics indicates the possibility of a pathogen resistant to all currently approved therapy. This proposal seeks to improve our understanding of this persistent pathogen by mentoring young investigators in clinical and translational patient oriented research of staphylococci.