Emergency Preparedness and Response
Cross-Species Immune System Reference
Performer: Stanford University School of Medicine
Principal Investigator: Dr. Garry Nolan
Translating results from animal models to human trials and therapies requires careful consideration of the similarities and differences any given animal species has when compared to humans. Inasmuch as other mammals have organs similar to our own (heart, liver, kidneys, etc.), the immune system is composed of functional components that are similar, but not identical, when comparing humans to other animals. Understanding where immune functions are similar in humans and animal models, and critically knowing where they are different, will help FDA and the biomedical research community to evaluate medical countermeasures and, eventually, aid in evaluating and delivering better countermeasures and therapies.
Stanford researchers will use mass cytometry to enable the first single-cell comprehensive cross-species analyses of immune system function by mapping the immune responses to certain biothreat agents and possible medical countermeasures in humans and animal models. Mass cytometry is a new technology that enables scientists to take simultaneous measurements of dozens of features located on and in cells and to analyze immune cells in far more detail than was previously possible. Given that the immune system is the key “first responder” to disease threats, it follows that how the immune system responds in the first minutes and hours can determine the health outcome for the host—be it human or animal.
With this project focus in mind, human and animal immune responses will be used to create species-specific immune function maps. Employing advanced computational techniques, the maps will be overlaid to highlight differences and similarities. The resulting data—and analysis tools to evaluate results—will be made available to the community through an open-access resource.
This project will:
- Expand our understanding of the potential toxicity of medical countermeasures in development
- Enable us to better understand how candidate countermeasures work (for example, what the mechanism of action is and whether there are unanticipated off-target effects that are beneficial)
- Enable us to examine the potential impact of host factors, such as age or whether the host is male or female
- Expand our knowledge of how biothreat agents affect host immune physiology
- Enable comparison of results from experiments conducted in cells from animals to cells from humans, as well in vivo experiments in animals
The data from these studies may help both to identify new biomarkers of disease and interpret studies performed in vitro and in animals to support the identification and development of countermeasures against CBRNE agents. Moreover, the tool box of reagents (substances or compounds that are added to a system to bring about a chemical reaction, or to see if a reaction occurs) being developed under this proposal and the data generated will inform studies far beyond those focused on CBRNE agents. The end result will translate into improved public health and better states of preparedness against emerging diseases and CBRNE threats.