Patient Oriented Research Program in ALI/ARF

急性肺损伤（ALI）是一种严重的肺损伤，在美国每年有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，其特征是氧合和通气的深刻改变。尽管在这些危重患者的护理方面取得了进展，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，指导是我目前学术职位中最重要、最充实的部分。我完全致力于指导，天生就喜欢与学员共同发展成功的愿景，并感谢有机会在他们的生活和事业中发挥作用。在我现在的K24的支持下，我已经担任了16名初级或中级研究员进行ALI/ARF患者导向研究的主要导师或联合导师。其中88%（14/16）仍在学术医学领域工作。在不到四年的时间里，这些学员已经获得了4项超过500万美元的新资助，还有4项NIH资助正在审查或准备重新提交。他们还撰写了24篇研究论文，9篇综述文章/社论，5篇正在提交的研究论文，以及29篇我是资深或共同作者的ATS摘要。尽管我们的工作效率很高，但在这次竞争激烈的更新中，我们提出了几个新的项目，这些项目将进一步促进我的职业发展，并为我们所有现在和未来的学员提供培训。随着我们全市范围的研究网络的建立，我们有能力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需要在指导和领导技能方面接受高级培训，以便为他们成为下一代ALI/ARF导师做好准备。此外，我将为我们更多的初级研究人员创造新的培训机会，并努力吸引其他多学科领域的学员。在这篇更新中，我们还提出了两项研究，这将有助于改善我们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基础上，并确定简单的床边技术用于诊断我们患者常见和衰弱的吞咽功能障碍的实用性。在第二项转化研究中，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会通过氧化剂依赖性RhoA激活改变ALI消退阶段凋亡炎性细胞的清除。在这种竞争性更新的支持下，我将能够继续发展我们的研究项目，并最终使我们成为美国首屈一指的ALI/ARF研究小组之一。

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.