Principal Investigator Alex Shalek
Our biological applications focus on how cellular heterogeneity and cell-to-cell communication drive ensemble immune responses in different contexts, ranging from acute infection to cancer. Motivated to push our technologies, test the generality of our findings, and help drive forward several medically-relevant fields, we work and collaborate across an enormous breadth of tissues, organisms, and diseases. From these collective observations, we aim to construct generalizable theoretical models that can be experimentally validated in additional natural or engineered biological systems using existing or to-be-developed tools.
The immune system plays an important role in regulating homeostatic balance across tissues and individuals in the face of changing and challenging environments. Given the pivotal and outsized impact cell subsets (e.g., rare precocious DCs) can have on ensemble dynamics (e.g., global activation of an antiviral response and deactivation of inflammation), we aim to understand the functional consequences of variation in cellular composition across tissues, as well as how different immune cells adapt to changing environmental conditions.
Motivating questions in the lab include:(*) How can we perform observational and experimental studies to understand the fundamental units of tissues structure and function?(*) Can we derive basic principles governing homeostatic and pathogenic immune responses within tissues?(*) What dictates the evolution of clonal antigen-specific T & B cell responses?
To this end, we are several multiple tissues from multiple organisms across common sources of variation. By examining consistent and unique themes that emerge across these systems, we aim to extract basic principles that govern homeostatic and pathogenic immune responses within tissues. Ultimately, we intend to leverage this information to rationally engineer immune responses (e.g., in vaccines and immunotherapies).