Immune cell reprogramming
The immune system underpins nearly every aspect of human health. It is the body’s defense and maintenance network, yet it has limited effectiveness in preventing many diseases that emerge later in life. Health requires continuous monitoring, repair, and recalibration, but the immune system’s natural programming is not optimized for the chronic challenges of aging. It degrades over time.
To meet the challenges of aging and chronic disease, we are building a new framework for immune cell engineering: one that transforms biological matter into programmable matter capable of sensing, decision-making, and response within the human body. Using AI, synthetic biology, and advanced cell reprogramming techniques, we are developing technologies that allow immune cells to monitor their environment, and respond precisely when needed.
Ultimately, our goal is to build a shared toolkit for deploying immune cells as programmable devices for real-time health surveillance and therapeutic intervention. By equipping cells with engineered biosensors, signal processing capabilities, and functional responses, we aim to create systems that can detect early changes in tissue homeostasis and act to correct any emerging threat to our health. This foundation will enable earlier detection, prevention, more precise treatment, and new approaches to diseases ranging from cancer and neurodegeneration to inflammation and fibrosis.
Our focus areas:
- Frontier AI/ML modeling — Building, testing, and benchmarking novel foundation models for biology to predict the specific cellular changes needed to implement new immune functions.
- Synthetic immune biology — Equipping cells with programmable sensing, processing, and intervention/functional response capabilities.
- Advanced single-cell technologies — Developing, optimizing, and benchmarking new tools for multiomics to profile immune cell dynamics.
- Living systems — Engineered cells and organoids, lineage-tracking models, and in vivo platforms to measure immune cell behavior.
- Foundational principles of immunology — Understanding the mechanisms and triggers that shape immune cells and their responses, including function, behavior, and immunogenomics.
“The conjunction of AI models plus the availability of computing power is leading to a shift from watching the immune system work to actually predicting what it will do next. With today’s tools, we can rewire immune cells to detect disease, report on physical changes, and deliver therapeutics.” — Andrea Califano, president of immune cell reprogramming
News
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Andrea Califano: 6 strategies for using AI to reprogram the immune system
The convergence of machine learning, synthetic biology, and immunology is changing what's possible for human health.
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Axios: Zuckerberg and Chan bet AI can cure all disease
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Associated Press: Zuckerberg, Chan shift bulk of philanthropy to science, focusing on AI and biology to curb disease
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Research
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Tissue-specific clonal selection and differentiation of CD4⁺ T cells during infection
Roham Parsa, Helder Assis, Tiago B.R. de Castro, et al. (2025) | bioRxiv
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Global organelle profiling reveals subcellular localization and remodeling at proteome scale
Marco Hein, Duo Peng, et al. (2025) | Cell
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Tabula Sapiens reveals transcription factor expression, senescence effects, and sex-specific features in cell types from 28 human organs and tissues
Stephen R. Quake, The Tabula Sapiens Consortium (2024) | bioRxiv
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