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The immune system is a spatially distributed, whole-body sensory-reactive system that monitors, reacts, and adapts to various stress signals (e.g., tissue damage, cell stresses, and pathogens) to maintain health and homeostasis in organ and physiologic systems. Thus, it is not surprising that the immune system has been implicated in diverse disease and health conditions beyond those classically thought of as immune-mediated, such as infection, vaccination, autoimmune, and anti-tumor responses. The status of the immune system can thus serve as a window into physiologic functions in health and disease to inform immune response outcome, future health trajectory, and interventional targets at both the population and individual level to improve current and future health.

Key Goal

A major hurdle towards realizing this vision is our lack of quantitative and predictive tools for understanding the behavior of the human immune system. Beyond trial-and-error tinkering, this level of predictive capacity and understanding is also required to leverage the immune system and its cells as platforms for precision engineering of sensors and therapeutic actuators. Immune function and responses are orchestrated by complex networks of molecules and cells interacting over the entire body and over time. While decades of fundamental advances in immunology have revealed the identity and function of key molecules, cells, and the associated pathways involved, how their collective interactions give rise to immune function and response outcome (e.g., to cancer immunotherapy), how those responses differ across individuals in the human population (e.g., resilient vs. poor responders to COVID-19), and when and how to intervene, remain extremely challenging questions to answer. For example, we do not yet have the tool to predict de novo the quantitative extent by which the antibody response would be altered if we doubled the dose or changed the dosing schedule of a vaccine – such capabilities would dramatically accelerate our ability to design and deploy immune interventions and therapeutics. Thus, a key research goal of the CSEI is to develop tools and concepts to achieve a quantitative and predictive understanding of the human immune system.

Key Theme

While the specifics of a particular disease and pathological condition are important, the CSEI’s overarching goal is to understand and engineer the immune system as a “single” system operating under different parameter regiments that correspond to different conditions. Our approach is to focus on fundamental circuitries and design principles conserved in various functional contexts, from vaccination and infection to autoimmunity and organ system surveillance – a key theme is to understand and engineer the interaction between the immune system and physiology.

The research activities of the CSEI are organized by Technology Platforms and Scientific Programs, which currently include:

Scientific Programs

  1. Immune system and physiology
  2. Tissue surveillance and early disease detection (e.g., in cancer, autoimmunity, and metabolic/inflammatory diseases)
  3. Nature, nurture, and human immune variability: human immune system states and responses throughout the lifespan and across the globe
  4. Design principles

Technology Platforms

  1. Molecular and cellular multiomics
  2. Predictive immune cell engineering
  3. Molecular recognition and immune repertoires
  4. Computational biology and biophysics