Molecular phenotypes of frailty in lung transplantation

PROJECT ABSTRACT I am an Associate Professor and lung transplant pulmonologist deeply committed to mentoring. I have developed a well-funded research program focused on applying aging-related research principles to define factors that impact patient-centered outcomes before and after lung transplant. Relevant to this K24 proposal, I led multicenter efforts that showed that frailty, sarcopenia, and high adiposity were prevalent and novel risk factors for disability, poorer health-related quality of life (HRQL), peri-operative complications, and death before and after transplant. My work has informed international guidelines on lung transplant candidacy, professional society statements, and NIH funding priorities. I am fortunate to have a diverse pool of resources including NIH funding; a cross-Departmental UCSF research program in advanced lung disease and transplant that I founded and direct; an outstanding research environment at UCSF with a large pool of potential mentees; and a network of collaborators throughout the country that I work closely with as part of multicenter cohort studies I lead or co-lead. Increasing clinical responsibilities, however, have limited my own career development and my ability to support a larger pool of mentees, especially those working to transition to independence. I have a diverse mentoring committee of seasoned investigators, themselves K24 recipients, who helped me to develop a tailored mid-career development plan. This plan includes didactics and experiential trainings in aging and gerontology and with expert collaborators to learn high-dimensional approaches to analyzing biomarkers and to deepen my experience with advanced and novel causal inference approaches to analyzing complex, longitudinal datasets. This plan also includes mentorship and leadership training. I will leverage this training and collaborators on this award to advance my work in in frailty in new directions. We will investigate our newly described molecular subphenotypes of frailty. To do so, we will leverage participants, data, and research infrastructures of multicenter R01 and two U01s that I am PI/MPI on and add discrete new measures. With this K24, we will examine the heterogenous pathobiology of pre- and incident post-operative frailty and determine whether this heterogeneity confers differential risk for pre-, peri- and post-operative complications in lung transplant including in older adults. The new research directions proposed and career development will make my program attractive to a diverse pool of mentees including those training in geriatrics, surgery, other solid-organ transplant fields, nursing, and those interested in interventions and health services. My areas of research expertise are unique in transplant. With my existing funding and support of this K24, I am well-positioned and committed to supporting trainees to develop fulfilling and sustainable research careers.