Wednesday, January 15, 2025
1/15/2025
Project Summary Solid organ transplant (SOT) recipients are a growing population of immunocompromised patients at increased risk for infection. Bacterial bloodstream infections (BSI) are common, affecting approximately 26% of SOT recipients after transplant. Mortality from BSI can reach up to 50% in SOT patients when accompanied with septic shock. The host immune response is believed to play a pivotal role in determining clinical outcomes from an infection in a SOT recipient, the details of which are poorly understood. Identifying immunologic biosignatures that portend prognostic information will lend biological insight into the mechanisms of maladaptive immune responses to BSI. I will use existing biological specimens from SOT recipients with BSI to test my overarching hypothesis that serum levels of cytokines, chemokines, immunoglobulin (IG), and differential gene expression profiles are associated with clinical severity of infection in SOT patients with bacterial BSI. The Specific Aims of this proposal are: Aim 1: Identify cytokine, chemokine, and IG biomarkers of septic shock and 30-day mortality among SOT recipients with BSI. Aim 2: Determine differential gene expression profiles and genetic pathways associated with septic shock and 30-day mortality in SOT patients with BSI. Aim 3A: Use immunologic biosignatures to develop a prognostic model for SOT patients with BSI. Aim 3B: Externally validate and refine the prognostic model using samples I will prospectively collect from SOT patients with BSI at Emory Transplant Center. I expect that completion of these Aims and related training will lead to a better understanding of how the host immune response influences outcomes in SOT patients during BSI. This information will directly inform future studies aimed at evaluating immunomodulatory treatment strategies to optimize outcomes of SOT patients with BSI. My long-term career goal is to become an independent physician scientist leading a team dedicated to improving outcomes in SOT recipients with bacterial infections. To facilitate my success in completing the Specific Aims, proposed training, and transition to a new institution, I have assembled an experienced team of mentors and advisors dedicated to training the next generation of physician scientists. Emory University School of Medicine is an ideal research environment for my proposal and training. As home to one of the nation’s top transplant centers, Emory is a highly collaborative research environment equipped with rich resources and national leaders in biomedical research. Therefore, I will be well positioned for success in developing the expertise and preliminary data necessary to compete for an NIH R01.
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