Mentorship in Pulmonary Vascular Disease

摘要肺动脉高压是一种罕见的以进行性肺血管为特征的肺部疾病。 闭塞导致右心衰竭并最终死亡。在过去的三十年里， 然而，在理解疾病机制方面取得了巨大的进步，导致了新的治疗方法 对于大多数患者来说，确诊后大约8年的存活率仍然很低。已经有几个 最近NIH/NHLBI赞助了关于PAH患者的表型和移动积累的“基因组”的研讨会 将数据输入临床以推进PAH的精准医学，但这项工作所在的中心很少 对下一代研究人员进行这些技术的持续和培训将是至关重要的 更广泛地推进PAH治疗和肺血管疾病领域。海恩斯医生是一口井- 她是该领域公认的专家，她的目标是利用K24职业中期调查员奖的支持 在以患者为中心的研究中着力培养下一代带来精准医学的科学家 肺动脉高压患者的治疗方法。候选人的近期和长期职业目标直接体现在 符合NIH K24奖项的目标，为获奖者提供保护时间的支持 为学生、住院医生、研究员和初级教员提供以患者为导向的研究和对文化敏感的指导。 具体地说，这一奖项将使她能够专注于(1)以患者为中心的研究计划的发展 肺血管疾病研究和(2)一个指导计划，以促进新的职业发展 调查人员。这一奖励将为候选人提供专门致力于开发的时间 以病人为中心的研究中的指导技巧。她的目标是招募和指导学生、住院医生、研究员 和初级教员，为在肺血管疾病方面成功的临床研究事业和支持 她目前的实习生是研究员和初级教员，他们的职业发展。来扩展她的位置 在PAH以患者为中心的研究计划中，她将在她的研究组合中结合两个研究方向(1) 了解脂轴中的胰岛素抵抗如何易患PAH或影响预后，以及(2)使用 肺血管疾病深部表型患者的基因组学技术。这里的建议将建立在 她资助的工作是测试多环芳烃的基因组签名可以识别对多环芳烃的弹性特征这一假设 进展与代谢干预易感性。具体目的是(1)比较PAH患者和 没有代谢功能障碍的基因组特征，定义临床和分子特征的差异 测量两组之间的相关结果，(2)检验和验证二甲双胍的经济学预测因素 在已完成和正在进行的PAH患者临床试验中的反应。完成这些目标将增强 了解PAH的发病机制并发现可能改进的代谢治疗策略 尤其是多环芳烃的疾病。提议的新研究，以及候选人的其他资助研究 这些项目将为以患者为中心的肺血管疾病研究提供宝贵的培训机会。

Pulmonary arterial hypertension (PAH) is a rare lung disease characterized by progressive pulmonary vascular obliteration resulting in right ventricular failure and ultimately death. Throughout the last three decades there has been tremendous progress in understanding disease mechanisms that have led to new therapies, however survival remains poor at approximately 8 years after diagnosis for most patients. There have been several recent NIH/NHLBI sponsored workshops on phenotyping patients with PAH and moving accumulating “Omic” data into the clinic to advance precision medicine in PAH, yet there are few centers in where this work is ongoing and training the next generation of researchers in these techniques will be critically important to advancing the field of PAH therapy and pulmonary vascular disease more broadly. Dr. Hemnes is a well- recognized expert in this field and her objective is to use the support of the K24 Midcareer Investigator Award in Patient-Oriented Research to focus on training the next generation of scientists to bring precision medicine approaches to PAH patient therapy. The candidate’s immediate and long-term career objectives are directly in line with the goals of the NIH K24 award, to provide support for protected time for awardees to devote to patient-oriented research and culturally-sensitive mentoring for students, residents, fellows and junior faculty. Specifically, this award will allow her to focus on the development of (1) a patient-oriented research program in pulmonary vascular disease research and (2) a mentoring program to facilitate the career development of new investigators. This award will provide protected time for the candidate to devote specifically to developing mentoring skills in patient-oriented research. Her objective is to recruit and mentor students, residents, fellows and junior faculty for successful clinical research careers in pulmonary vascular disease and to support the career advancement of her current trainees who are fellows and junior faculty members. To expand her patient-oriented research program in PAH, she will combine two lines of study in her research portfolio (1) understanding how insulin resistance in the lipid axis may predispose to PAH or affect outcomes and (2) using Omic techniques to deep phenotype patients with pulmonary vascular disease. The proposal here will build on her funded work to test the hypothesis that Omic signatures in PAH can identify features of resilience to PAH progression and metabolic intervention susceptibility. The specific aims are (1) To compare PAH patients with and without Omic signatures of metabolic dysfunction, define differences in clinical and molecular features and measure relevant outcomes between the two groups, (2) To test and validate Omic predictors of metformin responses in completed and ongoing clinical trials in PAH patients. Completion of these aims will enhance understanding of the pathogenesis of PAH and uncover potentially improved treatment strategies of metabolic disease in PAH specifically. The proposed new research, along with the candidate’s other funded research projects, will provide invaluable training opportunities in patient-oriented pulmonary vascular disease research.