Friday, May 3, 2024
5/3/2024
PROJECT SUMMARY/ABSTRACT This Mentored Patient-Oriented Research Career Development Award proposal will provide didactic and experiential training, expert mentorship, and an exceptional research environment to facilitate Dr. Caitlin Elgarten's development as an independent clinician scientist. Dr. Elgarten's long-term career goal is to develop strategies that use targeted measurement and manipulation of the microbiome to predict and prevent adverse outcomes of pediatric stem cell transplant (SCT). Although SCT offers a chance for cure for more than 1,500 children each year with life-threatening disorders of the hematologic and immune systems, the success of this treatment is limited by aberrant and/or delayed recovery of the new immune system leading to graft-versus-host disease (GVHD), serious infection and reduced survival. In this proposal, Dr. Elgarten will leverage data from three pediatric cohorts to characterize the disruption of the gastrointestinal tract microbiome that occurs during SCT. She will define the microbiome features that associate with acute GVHD and peripheral immune cell recovery, and identify the pharmacologic drivers of clinically relevant microbiome disruption. Through the adaptation of non-linear mixed effects models for repeated measures to model the multidimensional and highly dynamic nature of the microbiome, this study will deliver a greater understanding of the causal association of the microbiome and immune events after SCT. In doing so, this work will lay the foundation for identification of novel biomarkers and the rational design of interventions to improve SCT outcomes. Execution of these aims will also provide the candidate with essential experience in conducting observational microbiome research and with critical training in the advanced bioinformatics and statistical methods necessary to study the interaction of the microbiome, pharmacologic exposures and clinical factors that define risk for adverse outcomes after SCT. The candidate is a pediatric oncologist and SCT physician with formal training in pharmacoepidemiology and a background in clinical research focused on supportive care in SCT. She aspires to bring her perspective as a clinician and epidemiologist to the study of longitudinal microbiome change in this complex clinical scenario. Dr. Elgarten's goals for the K23 program are: 1) conduct a patient-oriented research project that will yield clinically meaningful results, 2) acquire bioinformatics skills for the analysis of microbiome sequencing data, and 3) develop a platform for analysis of longitudinal microbiome data in SCT based on non-linear mixed effects models for repeated measures. She has assembled a strong mentorship and advisory team, led by Dr. Brian Fisher, and inclusive of national experts in microbiome-host biology, deep sequencing methods and bioinformatics, quantitative model-based methods, and translational epidemiology. This guidance, combined with the extensive resources available at the Children's Hospital of Philadelphia and the University of Pennsylvania, will ensure the accomplishment of the proposed research and training goals and Dr. Elgarten's successful transition to independent investigator.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
