Mentored Patient Oriented Research in Lung Transplantation

指导以患者为导向的肺移植研究

• 批准号: 9751924
• 负责人: Jason D Christie
• 金额: $ 11.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-03 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751924
• 关键词: Acute Lung Injury; Address; Allografting; Alveolar Cell Type I; Assessment tool; Award; Biochemical; Brain Death; Clinical; Clinical Investigator; Clinical Trials; Complement; Complication; Conduct Clinical Trials; Critical Care; Critical Illness; Degree program; Diffuse; Donor person; Educational workshop; Ensure; Environment; Epithelial; Functional disorder; Funding; Future; Generations; Goals; Grant; Hypoxemia; Immunity; In Situ; Incidence; Injury; Investigation; Junior Physician; Knowledge; Lead; Life; Link; Longevity; Lung; Lung Transplantation; Lung diseases; Measures; Medicine; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Natural Immunity; Nature; Organ; Organ Donor; Outcome; PTX3 protein; Patients; Physicians; Population; Postoperative Period; Precision therapeutics; Prevention; Prevention strategy; Preventive therapy; Proxy; Pulmonary Edema; Recording of previous events; Reperfusion Therapy; Reporting; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Role; Savings; Scientist; Series; Smoke; Subgroup; Target Populations; Time; Training; Transplant Recipients; Transplantation; Writing; base; career; career development; circulating biomarkers; cost; design; experience; exposure to cigarette smoke; high risk; immune activation; implantation; improved; improved outcome; injury prevention; innovation; insight; interest; lung injury; molecular marker; mortality; novel; operation; patient oriented research; predictive modeling; prevent; prognostic; programs; protein biomarkers; receptor for advanced glycation endproducts; responsible research conduct; screening; skills; success

The goals of the proposed K24 renewal are to continue to devote time to dedicated mentorship of new clinical investigators, engage in career development to enhance my own mentoring skills, and facilitate transition to independence for future POR leaders. These goals will be accomplished through sustained reduction in Dr. Christie's clinical and administrative responsibilities with a resultant increase in effort spent directly on mentoring activities, expanding Dr. Christie's research program to include further investigation of the donor lungs, and acquisition of new research and mentoring skills. Dr. Christie's successful research program investigating acute lung injury following lung transplantation (termed primary graft dysfunction, PGD) will be expanded to provide trainees with an intensive research experience complemented by career development activities including didactic coursework in degree programs, research seminars, grant writing workshops, and training in responsible conduct of research. The proposed renewal of the K24 research will address the hypotheses that donor smoke exposure is associated with epithelial injury and innate immune activation that begins in the donor in situ, and that PGD can be predicted using molecular markers of innate immunity, epithelial injury, and donor smoke exposure pre-operatively in donors. PGD is severe acute lung injury occurring in the days after lung transplantation and has a major impact on early morbidity, mortality, and cost. Evidence suggests that PGD is the end result of a series of injuries occurring in the donor lung from the time of brain death to reperfusion in the recipient. Therefore, potential donor organs are routinely discarded because of concern for PGD; further limiting the number of organs available for transplant. Under Aim 1, we will determine the association of donor smoke exposure with circulating markers of epithelial injury and innate immune activation in the donor prior to procurement, and with PGD post-operatively. Under Aim 2, we will determine and validate the predictive utility of circulating protein biomarkers of epithelial injury, innate immune activation, and donor smoke exposure for PGD when measured pre-operatively in donors. Fulfillment of our aims will enable prediction of PGD based on novel pre-operative donor markers of injury and immunity, provide new knowledge on the roles of donor innate immune activation and epithelial injury in PGD risk, develop an expanded research platform including more detailed donor characterization to benefit mentees interested in lung transplantation as well as in other forms of lung injury, and enhanced training for Dr. Christie in novel methods of prediction and endotype determination, as well as expanded training in mentoring.

拟议的K24更新的目标是继续花费时间来专门 新的临床研究人员的指导，从事职业发展以增强自己的 指导技能，并促进过渡到未来的POR领导者的独立性。这些目标 克里斯蒂博士的临床和行政管理持续减少将实现 责任，导致直接在指导活动上花费的努力增加， 扩大克里斯蒂博士的研究计划，包括对供体肺的进一步调查， 并获得新的研究和指导技能。克里斯蒂博士的成功研究计划 研究肺移植后急性肺损伤（称为原发性移植功能障碍， PGD​​）将被扩展，以为受训者提供丰富的研究经验的补充 通过职业发展活动，包括学位课程中的教学课程，研究 研讨会，赠款写作研讨会和负责任的研究培训。这 拟议的K24研究续约将解决供体烟雾暴露的假设 与上皮损伤和先天免疫激活有关，该激活始于供体的原位供体 并且可以使用先天免疫，上皮损伤的分子标记来预测PGD 和供体在供体前的供体烟雾暴露。 PGD​​是严重的急性肺损伤 在肺移植后的几天，对早期发病率，死亡率和 成本。有证据表明，PGD是捐赠者中一系列伤害的最终结果 从脑死亡的时候到接受者的再灌注。因此，潜在的捐助者 由于关注PGD，定期丢弃器官；进一步限制数量 器官可用于移植。在AIM 1下，我们将确定供体烟的关联 供体中上皮损伤和先天免疫激活的循环标记的暴露 在采购之前和PGD术后。在AIM 2下，我们将确定并 验证上皮损伤，先天免疫的循环蛋白生物标志物的预测效用 当供体术前测量时，激活PGD的供体烟雾暴露。 实现我们的目标将基于新颖的术前捐助者来预测PGD 伤害和免疫的标志，提供有关供体先天免疫角色的新知识 PGD​​风险中的激活和上皮损伤，开发一个扩展的研究平台，包括 更详细的捐助者表征使对肺移植感兴趣的受训者受益 以及其他形式的肺损伤，以及在新颖的方法中对克里斯蒂博士的增强培训 预测和内型确定，以及扩展的指导培训。