Patient Oriented Research Program in ALI/ARF

急性肺损伤(ALI)是一种严重的肺损伤形式，每年在美国有20万人受到影响。急性呼吸衰竭(ARF)是一种更常见的肺功能障碍类型，其特征是氧合和换气发生深刻变化。虽然这些危重患者的护理已经取得了进展，但进一步培养对ALI/ARF感兴趣的以患者为导向的研究人员将是必要的，以显著改善这些患者的预后。到目前为止，辅导是我目前学术地位中最重要和最有成就感的部分。我完全致力于指导，与生俱来地喜欢与我的学员发展共同的成功愿景，并感激有机会改变他们的生活和职业。在我现在的K24的支持下，我已经担任了16名初级或中级研究人员的主要导师或联合导师，进行以患者为导向的ALI/ARF研究。共有88%(14/16)的人仍在学术医学领域。在不到四年的时间里，这些受训人员获得了4笔超过500万美元的新补助金，还有4笔国家卫生研究院的补助金正在审查中或准备重新提交。他们还撰写了24篇研究文章，9篇评论文章/社论，5篇目前正在提交的研究文章，以及29篇我是资深作者或合著者的ATS摘要。尽管我们的工作效率很高，但在这次竞争性更新中提出了几个新的项目，这些项目将进一步加强我的职业发展，并为我们现在和未来的所有学员提供培训。随着我们全市研究网络的建立，我们能够很好地进行比较有效性研究(CER)研究。为了正确地领导这些努力，我需要提高我在CER研究方面的技能。我们越来越多的中层调查人员将需要在指导和领导技能方面进行高级培训，以便为他们成为下一代ALI/ARF导师做好准备。此外，我将为我们更初级的调查人员创造新的培训机会，并努力吸引来自其他多学科领域的学员。在这次更新中，我们还提出了两项研究，这两项研究将有助于改善我们的ALI/ARF患者的护理。第一项研究将建立在我们对ALI/ARF患者周围神经肌肉功能障碍的现有兴趣的基础上，并确定简单的床边技术用于诊断吞咽功能障碍的有效性，这种吞咽功能障碍在我们的患者中很常见，使人虚弱。在第二个翻译研究中，我们将继续探索酒精改变ALI易感性的机制，并确定酒精滥用是否通过氧化剂依赖的RhoA激活改变了ALI解决期凋亡炎症细胞的清除。在这次竞争性更新的支持下，我将能够继续发展我们的研究项目，并最终确立我们作为美国一流的ALI/ARF研究小组之一的地位。

Acute lung injury (ALI) is a severe form of pulmonary impairment affecting 200,000 people annually in the United States. Acute respiratory failure (ARF) is an even more common type of pulmonary dysfunction characterized by profound alterations in oxygenation and ventilation. Though advances in the care of these critically ill patients have occurred, further cultivation of patient-oriented investigators with an interest in ALI/ARF will be necessary to generate significant improvements in the outcomes of these patients. Mentoring is by far the most important and fulfilling component of my current academic position. I am completely committed to mentoring, inherently enjoy developing mutual visions of success with my trainees, and appreciate the opportunity to make a difference in their lives and careers. With the support of my present K24, I have already served as the primary mentor or co-mentor for 16 junior or mid-level investigators performing ALI/ARF patient-oriented research. A total of 88% (14/16) of them remain in academic medicine. In less than four years, these trainees have received 4 new grants in excess of $5,000,000 and have 4 more NIH grants under review or ready for resubmission. They have also authored 24 research articles, 9 review articles/editorials, 5 research articles presently under submission, and 29 ATS abstracts on which I am the senior or a co-author. Despite our productivity, several new programs are proposed in this competitive renewal that will further enhance my career development and the training for all of our present and future trainees. With the creation of our city-wide research network, we are well positioned to perform comparative effectiveness research (CER) studies. In order to properly lead these efforts, I will need to boost my skills in CER research. Our increasing number of mid-level investigators will require advanced training in mentoring and leadership skills in order to prepare them to become the next generation of ALI/ARF mentors. In addition, I will create new training opportunities for our more junior investigators and work to attract trainees from other multidisciplinary fields. In this renewal, we also propose two research studies that will lead to improvements in the care of our ALI/ARF patients. The first study will build upon our existing interest in peripheral neuromuscular dysfunction in ALI/ARF patients and determine the utility of simple bedside techniques for the diagnosis of swallowing dysfunction that is common and debilitating in our patients. In the second translational study, we will continue to explore the mechanisms by which alcohol alters the susceptibility to develop ALI and determine whether alcohol abuse alters the clearance of apoptotic inflammatory cells during the resolution phase of ALI through oxidant-dependent RhoA activation. With the support of this competitive renewal, I will be able to continue to develop our research program and ultimately establish ourselves as one of the premier ALI/ARF research groups in the United States.