Targeting Immune Dysregulated Endotypes in Sepsis (TIDES)

The goals of the TIDES study are to define additional prognostic molecular sepsis subphenotypes (Aim 1) using multi-omics and to identify candidate targetable pathways of immune dysregulation in pediatric patients with sepsis (Aim 2). Dr. Lindell is the principal investigator of this study. The TIDES study is funded by NIH K23GM159013 (2025-2028).

Genomic Evaluation for Novel Explanations of Sepsis Immune Susceptibility (GENESIS)

The GENESIS project will develop a rapid whole-genome sequencing panel to identify actionable inborn errors of immunity in pediatric patients with with sepsis. Leveraging the 2024 IUIS IEI gene list and CHOP’s rapid-turnaround genomics platform, the study will embed a high-yield gene list in an automated analytic pipeline and pilot the assay using the PARADIGM-SHIFT biorepository. Dr. Lindell is a co-principal investigator for this study. The GENESIS study is supported by seed funding from the CHOP Frontier Programs (2025-2026).

Targeting Pulmonary Vascular Inflammation in Severe Pediatric Bronchiolitis (EFU-Bronchiolitis)

EFU-Bronchiolitis is a prospective multicenter cohort study investigating the role of dysregulated IL-1 signaling in hypoxemic respiratory failure among children with severe bronchiolitis requiring mechanical ventilation. The study aims to identify molecular drivers of endothelial cell dysfunction and pulmonary capillary leak, with the ultimate goal of developing markers of disease severity and repurposing IL-1 inhibitors as potential therapies. Dr. Lindell serves as a co-investigator for this study. The EFU-Bronchiolitis study is funded by NIH R01HL176019 (2025-2029).

Pediatric Sepsis Biorepository and Clinical Database (PSBS)

The goal of this study is to test the feasibility of novel approaches to collect, process, and analyze biologic data representing the immuno-metabolic response to infection early in the sepsis course and link this information to relevant organ dysfunction based sepsis phenotypes using electronic health record (EHR) data. Dr. Lindell serves as co-investigator for this study. This study is funded by NIH R33GM146159 (2022-2025).

Linking Immunotypes and Outcomes in Pediatric Sepsis (LIONS)

The LIONS study employed a suite of translational immunology lab assays to identify latent subclasses of disease in pediatric sepsis patients based on cellular immune responses and inflammatory proteomics, associated these candidate immunotypes with clinical outcomes, and then studied the molecular mechanisms of one candidate immunotype identified through our preliminary data. The LIONS study was funded by NIH K12HD047349 (2022-2024).

Serial High-Dimensional Immunophenotyping and Functional Testing in Pediatric MODS (PARADIGM-SHIFT)

The PARADIGM-SHIFT project built a prospective, longitudinal human biorepository of human plasma and peripheral blood mononuclear cells derived from children with multiple organ dysfunction syndrome. These biospecimens allowed for identification of disease-specific immunotypes using cellular and molecular immune profiling assays. The PARADIGM-SHIFT study was supported by the Thrasher Research Fund, the CHOP Research Institute, and institutional startup funds (2019-2022).

Transfusion and Organ Dysfunction in Pediatric Septic Shock (TROPICS)

TROPICS is a prospective observational study of pediatric septic shock which seeks to use machine learning to identify factors which should guide packed red blood cell transfusion decision making and identify immune phenotypes that predict differential response to pRBC transfusion. Dr. Lindell serves as site PI for TROPICS at CHOP. The TROPICS study is funded by NIH R01HL157208 (2022-2027).

PediAtric ReseArch of Drugs, Immunoparalysis and Genetics during MODS (PARADIGM)

PARADIGM was a 22-center prospective study of disease-, treatment-, and genomic-based risk factors for severe immunoparalysis in the setting of pediatric MODS. Dr. Lindell served as site PI for PARADIGM at CHOP. The PARADIGM study was funded by NIH R01HD095976 (2019-2024).