Critical Care Mitochondrial Unit
Understanding Mitochondrial Dysfunction in Pediatric Critical Illness
The Critical Care Mitochondrial Unit (CCMU) at Nemours Children’s in the Delaware Valley studies how cellular energy failure contributes to organ dysfunction in children with critical illness. When mitochondria, the structures responsible for producing energy inside cells, do not function properly, cells cannot meet the demands of severe illness. This disruption can lead to organ failure, immune dysregulation, and delayed recovery.
Children with critical illness do not follow the same path to recovery. Some recover quickly. Others experience chronic organ injury or ongoing inflammation despite receiving timely, evidence-based care. Our research examines why these differences happen and how failures in cellular energy production and repair contribute to poor outcomes.
Our work focuses primarily on pediatric sepsis, a life-threatening response to infection and a leading cause of childhood mortality worldwide. We also study shock, diabetic ketoacidosis, acute kidney injury, and injuries related to surgery or trauma. Our goal is to help improve treatments so children with critical illness can recover more fully and live healthier lives.
Principal Investigator
Scott L. Weiss, MD, MSCE
Principal Research Scientist
Division Chief, Critical Care, Nemours Children’s Health, Delaware
Vice Chair, Nemours Research, Delaware Valley
Professor of Pediatrics and Pathology & Genomic Medicine, Sidney Kimmel Medical College at Thomas Jefferson University
Research Team
LEARN MORE ABOUT OUR RESEARCH
- Research Interests
- Notable Projects
- Impact & Affiliations
- Grants & Support
Our Areas of Focus
Pediatric Sepsis & Severe Infection
We study how mitochondrial dysfunction drives organ failure and persistent inflammation in children with sepsis, and why cellular recovery fails in some patients during and after critical illness.
Shock & Acute Critical Illness
Our research examines shared cellular pathways across shock states, surgical complications, and traumatic injury to identify treatment strategies that may benefit children with a variety of conditions.
Metabolic & Kidney-Related Critical Illness
We investigate mitochondrial dysfunction in conditions such as diabetic ketoacidosis and acute kidney injury, clarifying how metabolic stress and vascular injury contribute to organ dysfunction in children.
Recovery & Long-Term Outcomes After Critical Illness
Beyond survival, we study how cellular injury and immune disruption affect cognition, behavior, and infection risk after discharge, addressing an understudied area of pediatric recovery and quality of life.
Laboratory Infrastructure & Experimental Approaches
The CCMU is a translational research laboratory using high-resolution respirometry (Oroboros and Seahorse) alongside protein and nucleic acid assays to assess mitochondrial function. Our work integrates human samples, animal models, and cell lines to support pediatric research across the spectrum of critical illness.
Current Research Highlights
Mitochondrial Quality Control in Pediatric Sepsis
We're examining novel mechanisms that may be targeted to reverse organ dysfunction, the leading cause of death in children with sepsis, for which there are currently no therapeutic options.
Early & Persistent Mitochondrial Dysfunction in Pediatric Sepsis
Our team is evaluating whether the mitochondrial adenine nucleotide translocator (ANT), which is necessary for cellular energy utilization as ATP, is depleted early in sepsis and fails to recover in children with persistent mitochondrial dysfunction, refractory shock, and inflammation.
Mitochondrial Dysfunction & Neurobehavioral Outcomes After Sepsis
We're investigating whether mitochondrial dysfunction and neuronal injury in the hippocampus and prefrontal cortex contribute to the development and severity of neurobehavioral deficits in a mouse model of sepsis survivorship.
Sodium Butyrate to Protect Kidney & Liver Mitochondria
Our researchers are studying whether sodium butyrate prevents or reverses lipopolysaccharide-induced mitochondrial dysfunction in kidney and liver tissue using a mouse model.
Kidney Mitochondrial Dysfunction in Sepsis & Diabetic Ketoacidosis
Our team is leveraging natural variation across two pediatric critical illnesses with known endothelial injury to test whether endothelial injury is associated with systemic mitochondrial dysfunction and exacerbated by plasma cytokines and matrix metalloproteinases that impair mitochondrial function within endothelial cells.
Long-Term Immune Dysfunction After Pediatric Sepsis
Our researchers are evaluating whether immune dysfunction characteristic of acute sepsis persists or worsens after recovery from sepsis and if these changes are associated with increased risk for new infections after discharge.
How We're Making a Difference
Our translational studies have established foundational knowledge about mitochondrial dysfunction in pediatric critical illness. Key contributions include:
- Making mitochondrial dysfunction measurable at the bedside through blood-based assays that identify which children have this problem, enabling personalized treatment approaches.
- Establishing clinical significance by demonstrating a direct relationship between mitochondrial dysfunction severity and organ failure, confirming this as a therapeutically relevant target.
- Identifying sodium butyrate as a promising therapeutic candidate to protect mitochondrial function following microbiome disruption during critical illness, opening a new avenue for organ-protective interventions.
- Pioneering research into long-term outcomes by examining how mitochondrial injury in the brain may contribute to learning and behavioral challenges in survivors, addressing quality of life beyond hospital discharge.
Research Collaborations
Our team works in close partnership with researchers at Nemours and leading academic medical centers to advance understanding of mitochondrial dysfunction across pediatric critical illnesses.
Internal partners include the Dynamics in Epilepsy and Cognitive Development (DECODE) Lab at Nemours. External collaborators include the MitoCare Center for Mitochondrial Imaging Research at Thomas Jefferson University and the Center for Mitochondrial and Epigenomic Medicine at Children’s Hospital of Philadelphia.
We also participate in national pediatric sepsis research networks that support multicenter biorepository development and clinical trials.
Grant Funding
Federal and institutional funding supports our efforts to translate lab findings into insights that improve recovery and long-term outcomes for children. This investment reflects the clinical relevance of our research. Recent support includes:
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
R01 Grant | Effect of Mitochondrial Quality Control on Systemic Inflammation and Organ Dysfunction in Pediatric Sepsis (2020-2026) | Weiss, S. L. (PI)
R01 Grant | PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS) (2020-2025) | Weiss, S. L.; Balamuth, F. (Co-PIs)
National Institute of General Medical Sciences (NIGMS)
R21/R33 Grant | Pediatric Sepsis Biorepository and Clinical Database (2022-2027)
Balamuth, F.; Sanchez-Pinto, L. N. (PIs)
Institutional Support
Nemours Research
Comparative Analysis of Kidney Mitochondrial Dysfunction in Pediatric Sepsis and Diabetic Ketoacidosis (2025-2027) | Roy Chowdhury, S. K. (PI)
Pediatric Award for Clinical Research (PACR)
Mitochondrial Dysfunction in Early and Late Phases of Pediatric Sepsis (2024-2025) | Weiss, S. L.; Tigano, M. (Co-PIs)
Publications
Nemours researchers constantly contribute to advancing scientific understanding. We share our knowledge, insights, and discoveries to encourage collaboration and inspire further research.
Research in Context
Our lab contributes to research that informs pediatric care and connects to broader areas of scientific study at Nemours.
Emergency Medicine Research
RESEARCH AREA
We improve pediatric emergency care through quality initiatives, innovation, and multi-site studies conducted in collaboration with national research networks.
Immunology Research
RESEARCH AREA
We investigate immune system function in children to advance understanding of autoimmune disease, allergy, immunodeficiency, and immunotherapy.
Neuroscience Research
RESEARCH AREA
We investigate brain development and neurological disorders to advance pediatric neuroscience through collaboration and translational science.
Pediatric Intensive Care
CLINICAL CARE
Critical care for children with serious illness or injury in specialized units at our Delaware and Florida children's hospitals.