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Principal Investigator: Caitlin Walfoort Elgarten
Organization: CHILDREN'S HOSP OF PHILADELPHIA
Fiscal Year: 2024
Award: $185,652
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <0-11 years old><Acute GVHD><Acute Graft Versus Host Disease><Address><Advisory Committees><Alimentary Canal><Allogenic><Anti-Infective Agents><Anti-Infective Drugs><Anti-Infectives><Anti-infective Preparation><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Behavior><Bio-Informatics><Bioinformatics><Biological Markers><Biology><Blood Diseases><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood leukocyte><Carbapenems><Cell Body><Cell Communication and Signaling><Cell Function><Cell Physiology><Cell Process><Cell Signaling><Cells><Cellular Function><Cellular Physiology><Cellular Process><Child><Child Youth><Childhood><Childhood Leukemia><Children (0-21)><Children's Hospital><Children's Oncology Group><Clinical><Clinical Research><Clinical Study><Complex><Concentration measurement><Data><Development><Digestive Tract><Disease><Disorder><Drug Kinetics><Drug Targeting><Drugs><Engraftment><Ensure><Environment><Epidemiologist><Epidemiology><Event><Exposure to><Foundations><Functional Metagenomics><Future><GI Tract><Gastrointestinal Tract><Gastrointestinal tract structure><Goals><GvHD><Healthcare><Hematologic Body System><Hematologic Diseases><Hematologic Organ System><Hematological Disease><Hematological Disorder><Hematopoietic Body System><Hematopoietic System><Hemoglobinopathies><High-dimensional Modeling><Homologous Wasting Disease><Human><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunologic><Immunologic Diseases><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunologically><Immunologics><Individual><Infection><Intervention><Intervention Strategies><Intervention Studies><Intracellular Communication and Signaling><Investigation><Investigators><K23 Award><K23 Mechanism><K23 Program><Kinetics><Knowledge><Leukocytes><Leukocytes Reticuloendothelial System><Life><Link><Long-term cohort><Longitudinal Studies><Longitudinal cohort><Longterm cohort><Lymphocytopenia><Lymphopenia><Marrow Neutrophil><Marrow leukocyte><Measurement><Measures><Mediating><Medication><Mentored Patient-Oriented Research Career Development Award><Mentored Patient-Oriented Research Career Development Award (K23)><Mentorship><Metagenomics><Methods><Microbiomics><Miscellaneous Antibiotic><Modeling><Modern Man><Nature><Neutropenia><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Outcome><Pathogenesis><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pediatric Hospitals><Pediatric Leukemia><Pediatric Oncologist><Pediatric Oncology Group><Pediatric cohort><Pennsylvania><Peripheral><Pharmaceutical Epidemiology><Pharmaceutical Preparations><Pharmacoepidemiology><Pharmacokinetics><Philadelphia><Physicians><Physiologic><Physiological><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Progenitor Cell Transplantation><Progenitor Cells><Prospective cohort><QOL><Quality of life><R-Series Research Projects><R01 Mechanism><R01 Program><Recovery><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Residual><Residual state><Resources><Risk><Runt Disease><Sampling><Scientist><Signal Transduction><Signal Transduction Systems><Signaling><Statistical Methods><Stem Cell Transplantation><Stem cell transplant><Subcellular Process><Supportive Therapy><Supportive care><System><Systems Development><Task Forces><Therapeutic><Time><Training><Transplant Recipients><Transplantation and Immune System><Universities><Validation><White Blood Cells><White Cell><Work><acute graft vs host disease><acute graft vs. host disease><adverse consequence><adverse outcome><advisory team><alimentary tract><analyze microbiome><analyzing longitudinal><behavior study><behavioral study><bio-markers><biologic marker><biological signal transduction><biomarker><blood disorder><bone marrow failure syndrome><career><children with leukemia><clinical relevance><clinical significance><clinically relevant><clinically significant><cohort><communicable disease control agent><deep sequencing><developmental><digestive canal><drug epidemiology><drug/agent><epidemiologic><epidemiological><experience><graft versus host disease><graft vs host disease><graft vs. host disease><health care><host microbiome><hypoimmunity><immune deficiency><immune reconstitution><immunodeficiency><improved><infection risk><inter-patient variability><interpatient variability><intervention design><intervention research><interventional research><interventional strategy><interventional study><interventions research><kids><kinetic model><leukemia><leukemia in children><long-term study><longitudinal analysis><longitudinal outcome studies><longterm study><microbial consortia><microbial flora><microbiome><microbiome analysis><microbiome research><microbiome science><microbiome sequencing><microbiome studies><microbiota><microflora><multidimensional modeling><multispecies consortia><neutrophil><new marker><novel biomarker><novel marker><patient oriented outcomes><patient oriented research><patient oriented study><patient variability><patient variation><pediatric><pharmacodynamic model><pharmacoepidemiologic><pharmacoepidemiological><pharmacologic><prevent><preventing><progenitor transplantation><rational design><response><skills><statistic methods><stem and progenitor cell transplantations><stem cells><success><therapy design><transplant patient><treatment design><validations><variability between patients><variation between patients><white blood cell><white blood corpuscle><youngster>