SYSTEMS TISSUE BIOLOGY
What rules govern how cells self-organize into functional tissues?
How do cellular interactions create stable and adaptive tissue states?
What causes these states to destabilize with age and disease?
spatial organization
and cell states
PERTURB
biological systems in vitro, in vivo,
in silico
MEASURE
MODEL
mechanisms across molecular, cellular, and tissue scales
PREDICT
responses, remodeling,
and failure
Predictive Tissue Biology
How do cells collectively produce tissue behavior? We build models to learn rules that connect cell states to circuits that are robust to noise and fluctuations.
Principles of cell circuit organization in tissues
Tissues maintain homeostasis by integrating constantly changing spatial and temporal signals into coordinated responses. Parenchymal and immune cells communicate through multicellular circuits that produce distinct homeostatic, pathological, or therapeutic states, yet the organizing principles of these circuits remain unclear. We combine theory-guided modeling with spatial and single-cell measurements to determine which configurations of cellular interactions generate stable tissue states. Ultimately, we aim to develop a predictive framework to understand and manipulate multicellular organization in tissues.
Mechanistic models of cell state heterogeneity
Genetically identical cells can respond very differently to the same signal or perturbation, yet the mechanisms that generate this heterogeneity remain poorly understood. We combine single-cell proteogenomics (inCITE-seq), rapid perturbations of gene-regulatory networks, and mechanistic modeling to determine how signaling pathways and epigenomic states interact to shape gene expression and produce persistent differences in cell behavior. By learning the rules that govern these responses, we aim to improve cell-fate prediction, accelerate drug discovery, and anticipate mechanisms of drug resistance.
Aging and Resilience
Why do some tissues repeatedly recover while others progress toward failure? We study how coordinated repair is maintained across multi-scale interactions and how it breaks down with age and disease, focusing on the ovary and vasculature.
Spatiotemporal dynamics of ovarian aging
The ovary is among the first organs to age. Its reproductive and endocrine functions depend on precisely coordinated changes in cell states, cellular composition, and tissue interactions across the reproductive cycle. We combine spatial profiling, in vivo lineage tracing, and machine learning to determine how this coordination breaks down with age, with a particular focus on immune and vascular dysfunction. Through studies in mouse models and human tissues, we aim to uncover fundamental principles of tissue aging and identify therapeutic strategies to preserve ovarian and endocrine health.
Aging disrupts spatiotemporal coordination in the cycling murine ovary. Cover of Nature Aging, June 2026
Vascular resilience in health and disease
Blood vessels must continually adapt to mechanical stress, inflammation, and injury while maintaining their structural integrity and function. We combine multi-omics, quantitative histology, and deep learning to determine how interactions among vascular smooth muscle cells, immune cells, and the extracellular matrix stabilize the vessel wall or drive its degeneration. By identifying the early events that distinguish adaptive repair from pathological remodeling in the aorta and coronary arteries, we aim to discover biomarkers of disease progression and therapeutic strategies that restore vascular resilience.
