Our Mission
The mission of our Center is to develop a comprehensive suite of technologies and analytical methods to measure and integrate the molecular and environmental determinants of cellular identity. While our Center’s original mission enabled a breadth of new techniques for high-resolution annotation of cell states, the true potential of single-cell multimodal analysis lies in its ability to not only catalog what cells are doing, but to explain why they are doing it. In our renewal phase, we propose that single cell multi-omics can pinpoint the fundamental molecular determinants that establish a cell’s identity and learn how cells integrate information across diverse regulatory modalities that direct their current and future states
Aims
Aim 1 — Understanding how RNA dynamics shape cell identity
Cells constantly transcribe, splice, and degrade RNA, and these dynamic processes play a major role in determining what a cell is and how it behaves. We will develop powerful new approaches to measure these rapid RNA life-cycle events at massive scale and across multiple molecular layers. By capturing transcriptional activity, RNA processing, and other molecular readouts together, we will uncover how different components of RNA regulation work in concert to define cellular states and decision-making.
Aim 2 — Revealing the regulatory logic that drives cell fate
A cell's identity is shaped not only by its current gene expression, but also by the regulatory landscape that guides its past and future decisions. We will create integrated single-cell technologies to measure the key molecular factors that control cell fate—such as transcription factor activity and epigenetic modifications. By connecting these regulatory layers within individual cells, we aim to explain how diverse molecular cues are integrated to produce stable identities and enable future changes.
Aim 3 — Mapping human cell lineages to understand plasticity and growth
Human tissues contain a rich history of lineage relationships—traces of cell ancestry that influence development, aging, and disease. We will develop scalable methods to read natural lineage marks from human samples and reconstruct high-resolution lineage trees. By combining lineage information with molecular profiles, we will reveal how clonal expansions arise, how lineage influences cell behavior, and how developmental history shapes cell identity and plasticity.
Aim 4 — Predicting and interpreting cellular responses across systems
Cells respond to their environment through coordinated, multimodal molecular changes. We will create and combine new experimental technologies with advanced computational approaches to understand and forecast these responses, modeling how molecular events unfold over time and developing methods to compare perturbation responses across diverse biological settings. These tools will allow researchers to interpret cellular behavior in vivo using growing datasets from controlled model systems.