Human Systems Biology of Inflammation

Inflammation is the most common condition seen in human diseases. Patient's response to systemic inflammation is a collection of physiological and pathological processes that depend critically upon the regulation of the human immune system. Understanding such complex disease processes requires a systems view of the whole human body, covering from the molecular level, cellular level, to the tissue and organ systems level.

 

The Inflammation and the Host Response to Injury consortium consisting of more than 100 participating investigators from 17 academic institutions (PI, Ron Tompkins) and many disparate scientific disciplines conducted large scale clinical studies on systemic inflammation in patients of Intensive Care Units since 2001. These include monitoring the clinical information of ~2,700 trauma and burn patients, and genomics, proteomics and functional analysis of blood and tissue samples of ~500 trauma patients up to 28 days after injury and ~270 burn patients up to 1 year after injury. In addition, human in vivo LPS modeland murine disease models were analyzed as comparisons.

 

Our systems biology research focuses on integrative analysis of these comprehensive genomic, proteomic, cellular, organ functional and clinical datasets to identify the mechanisms underlying human systemic inflammation, to compare and contrast human response to different inflammatory stresses and with murine models, to improve the classification and prediction of patient clinical outcomes, and to identify candidates for potential interventions. In addition, we aim to develop multi-scale disease models of inflammation as well as methods and computational tools for follow-up analysis. The new statistical and bioinformatic algorithms and software tools will be applicable for other large scale translational studies. Here are a few highlights of our work.

 

A. Mining Clinical Information for Better Patient Care

B. Studying the Genomic Response to Systemic Inflammation

  • Systemic inflammation introduces a genomic storm  in patients that affects all the major functions and pathways. This genomic response includes simultaneously increased expression of genes involved in the innate immune responses and  suppressed expression of genes involved in adaptive immunity.
  • Complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hitand differ only in the magnitude and duration of this genomic reprioritization.

 

 

 

 

 

 

 

 

 

 

 

 

  • The gene changes  are highly consistent in  patients of different inflammatory diseases, although the recovery time  varies from days to weeks to months.

 

 

 

 

 

 

 

 

 

 

 

 

 

 C. Early Prediction of Patient Outcomes

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

D. Analysis of Proteomic Changes in Patients

  • Blood plasma, T-cell and Monocyte samples from trauma and burn patients were analyzed.

 

 Below please find additional information on several selected projects.