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 currently under review by the NIH.

Multi-Omic Sepsis Analytics for Individualized Clinical Strategies (MOSAICS)

The goals of the MOSAICS study are to develop a rapid molecular diagnostic assay to identify prognostic sepsis endotypes in real time and to evaluate the therapeutic potential of JAK1/2 and STAT3 inhibition in reversing immune dysregulation in pediatric sepsis. Dr. Lindell is the principal investigator of this study. The MOSAICS study is under review by the Hartwell Foundation.

Linking Immunotypes and Outcomes in Pediatric Sepsis (LIONS)

This project employs 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, associate these candidate immunotypes with clinical outcomes, and then investigate the molecular mechanisms of one candidate immunotype identified through our preliminary data. Dr. Lindell serves as principal investigator for LIONS. The LIONS study is funded by NIH K12HD047349.

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.

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

EFU-Bronchiolitis is a prospective observational cohort study investigating the role of dysregulated interleukin-1 (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.

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

The goal of this project is to build a prospective, longitudinal human biorepository of human plasma and peripheral blood mononuclear cells derived from children with multiple organ dysfunction syndrome. These biospecimens will allow for identification of disease-specific immunotypes using cellular and molecular immune profiling assays. Dr. Lindell serves as principal investigator for PARADIGM-SHIFT. The PARADIGM-SHIFT study is supported by the Thrasher Research Fund, the CHOP Research Institute, and institutional startup funds.

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

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

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 (PRBC) 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.