Multiple ideas related to inflammation were submitted for the “Innovate to Accelerate” workshop. Discussion at the workshop explored whether these concepts could be combined into a single, comprehensive concept. For all concepts, the trans-NIH nature of the topic was noted, with relevance to multiple diseases and conditions and requiring a multi-disciplinary approach beyond the scope of a single NIH Institute or Center. The potential impacts of these programs would include a better understanding of inflammation in both healthy and diseased states, as well as laying the foundation for improved therapies.

Below are the concepts and summaries of discussion at the workshop. We welcome comments on how these ideas could be combined and synergized.

Cellular and Molecular Profiling of Inflammation
Chronic inflammation is at the root of nearly every chronic disease yet we do not have a good understanding of how inflammation qualitatively differs according to the disease- or tissue-type.  This concept would profile healthy people compared to those with chronic inflammation to create an “inflammalogue” which would describe normal and abnormal immune signatures in diverse tissues at molecular and cellular levels. This would ultimately enable development of anti-inflammatory treatments that are tissue- or condition-specific.

What would the goals of the program be?

  • Build an inflammalogue of homeostatic immunity, protective immune response vs chronic inflammation, using high throughput technologies such as RNA seq, metabolomics, proteomics, high resolution histology etc.
  • Characterize the contribution of the different cell types (immune cells vs stroma – fibroblasts, endothelials cells etc)
  • Determine  how systemic changes (peripheral blood) represent the changes that are occurring in the inflammed tissues
  • Develop in vivo tissue imaging tools to measure inflammation.
  • Develop data bases made available to the scientific and medical community
  • Determine changes in the inflammalogue in model diseases represented in murine models and patients.

What initiatives might form the strategic plan for this topic?

  • Creation of a Consortium on Inflammation and Disease: Data coordinating and data generating centers.
  • Selection of disease models for testing.
  • Development of training initiatives to educate the next generation researchers and clinicians on a Systems Approach to Inflammation and Disease

Homeostatic Inflammatory Response
This concept focused on the questions of: What’s the normal distribution of inflammation in a healthy reference population? How do we reliably quantify abnormal or unhealthy inflammation? How does the “inflammosome” change over the lifespan – in pregnancy, age, following acute infection or chronic disease? The program would involve cataloging inflammatory cells/molecular signals from healthy individuals and those with chronic disease; it would also develop imaging tools to detect and monitor inflammation earlier and more reliably in disease conditions. The discussion also highlighted the need to study the impact of stress, physical activity, and environmental exposures.

What would the goals of the program be?

  • Mining existing databases and systematic literature review
  • Animal model development replicative of human disease and inflammatory responses
  • Develop systems-biology based catalogue of inflammatory profile of several diseases relative to healthy reference state. These include (1) acute inflammatory response, such as acute viral pathogen, (2) autoimmune, (3) chronic disorder (such as obesity, asthma, etc.), (4) healthy reference populations.
  • Databases at cellular and tissue resolution of multi’omics profiles
  • Integrative databases for signature profiles of inflammation and fluctuations in healthy state in cohorts representative of discrete lifespan intervals
  • Development of imaging and molecular typing tools with quantitative components which are reproducible
  • Enable early detection of chronic disease, to facilitate primary and secondary prevention

What initiatives might form the strategic plan for this topic?
Near term goals:

  • Animal models
  • Data mining (integrative Human Microbiome Project (iHMP) and HMP2.0; human Epigenomics Roadmap demonstration projects; Clinical and Translational Science Awards (CTSAs))
  • Focus groups/iterative processes to define inflammation and notably causal inflammation

Implementation goals:

  • Clinical phenotyping coordinating center(s)
  • Develop real time imaging technology and data interpretation/integration with molecular measures
  • Data coordinating centers with capacity to integrate readily with Precision Medicine Initiative (PMI) centers/leverage PMI initiatives
  • Leveraging of existing or proposed subject cohorts for multi’omics

Metabolomics of Chronic Inflammation
This concept would involve metabolite profiling of normal and inflamed tissues, identification of metabolites that regulate inflammation, and development of probes to trace metabolites from one tissue to another. It would create tissue-specific metabolic signatures of inflammation with a goal of understanding the transition from a healthy state to a disease state.

What are the goals of the program?

  • Metabolite profiling of normal and diseased tissues/cells
  • Identify/validate which metabolites are involved in signaling in regulating inflammation
  • Develop new probes for tracing metabolites in vivo/ in situ
  • Develop animal models to test metabolic states and resultant changes in inflammatory state 
  • 10 year goal – advance toward development of anti-inflammatory drugs that have advantages over current therapies

What initiatives might form the strategic plan for the topic?

  • Create a consortium for developing new probes and/or best leveraging current technologies, specifically targeting metabolomics data collection in chronic disease, and addressing need for rapid data collection and analysis, including better and/or less invasive ways to collect patient samples.
  • Create a database for inputting this information in a maximally accessible format, taking advantage of the best features of current databases (e.g. Common Fund metabolomics database) and possibly developing improved databases specifically to address needs of this program.
  • Create a center for development and distribution of better animal models for studying the metabolomics of inflammation.
  • Create a panel for crosstalk between academics and pharmaceutical companies to promote a mutual understanding of what is needed for new targets to be identified and validated, and fund focused individual projects aiming to achieve such targeted validation.